key: cord- -lvcxrmih authors: shaw, ken title: the impact of diabetes on covid‐ infection date: - - journal: nan doi: . /pdi. sha: doc_id: cord_uid: lvcxrmih nan gence of this current novel coronavirus pandemic (sars-cov- / covid- ) from wuhan, china, it has become rapidly apparent that those with known preceding comorbidities are much more likely to develop life-threatening complications of pneumonia and acute respiratory distress syndrome. not unexpectedly, diabetes has been identified as posing a particular adverse risk, along with chronic renal and coronary heart disease, and such surrogate risk indicators as obesity and hypertension. actual susceptibility to infection with diabetes may be argued, but infection once acquired is likely to be more severe and prolonged, determined by a number of factors, including duration of diabetes, the presence of diabetes-related complications and the level of glycaemic control. sub-optimal blood glucose levels, compounded by the adverse vicious cycle of response to infection, increase vulnerability and adverse outcome. for a comprehensive review as to how the immune system may be disturbed with diabetes, the relevant chapter, 'infection and diabetes', in joslin's diabetes mellitus is to be recommended. for example, studies are described reporting defects of cell-mediated immunity and diminished lymphocyte transformation response in people with poorly-controlled diabetes, while impaired leucocyte function, the first line of defence against secondary bacterial infection, can be demonstrated from observation of reduced phagocytic activity with increasing levels of blood glucose. such disturbances of immune function are very likely to have significant impact on the outcome of covid- infection complicated by diabetes. furthermore, it has been suggested that increased glucose concentrations in airway secretions may expose pulmonary epithelial cells to greater viral replication and consequent pneumonitis. although criticism has been levelled concerning the transparency of the early coronavirus epidemic experience in china, several preliminary clinical and epidemiological papers, summarised in a recent practical diabetes editorial, have achieved rapid publication - primarily listing diabetes simply as an adverse comorbidity, more prevalent in severe cases and with non-survivors. these early reports of covid- infection included observations of critically ill adult patients with coronavirus pneumonia admitted to the icu at the wuhan jin yin-tan hospital, where diabetes was found in twice the number of individuals who died compared to those who survived ( % vs %). this outcome has since been replicated on a wider scale from hospitals across china where, in a total of patients with established covid- infection, diabetes was present in . % of cases overall, but recorded in a significantly greater proportion of those with severe compared to non-severe disease ( . % vs . %). a small sample analysis of fatalities reported diabetes in . % of cases. further reports from wuhan have since been published, with continued indication of diabetes as a risk factor for the progression and prognosis of covid- infection. one study has observed that % of cases had diabetes without any other comorbidities, but nonetheless these individuals were at much higher risk of developing severe pneumonia, excessive release of inflammatory bio-markers and increased hypercoagulability. this 'inflammatory storm' was associated with a more rapid deterioration of illness and a significantly higher mortality rate. from analysis of patients, predictors of fatal outcome included older age, the presence of other underlying diseases, the onset of secondary infection and elevated inflammatory markers. in fatal cases, five ( %) patients died with myocardial damage, described as 'fulminant myocarditis' consequent to the 'cytokine storm'. working in central london as a junior doctor during the hong kong flu pandemic, one recollects that deaths in young individuals were often attributed to viral myocarditis. it is a salutary reflection as to how diabetes has exploded in this modern age, barely recognised as a clinical issue years ago. in the western world, the university hospital of padua, at the epicentre of the outbreak in italy, reports that . % of patients dying from covid- infection had diabetes, compared to a matched population prevalence of . %, while in preliminary estimates from the usa, based on data from , persons with confirmed covid- disease, diabetes proved to be the most significant medical comorbidity: . % of total; % of those hospitalised and % of those admitted to the icu. so far data for the uk are limited. however, the office of national statistics has reported that in england and wales % of those dying from covid- infection had at least one pre-existing condition, including diabetes. more specifically, statistics from nhs england for the period march to may record that of , covid- deaths in hospital, ( %) had diabetes, a comparable proportion to new york city, with diabetes identified in % of patients hospitalised with covid- infection. parallels have been drawn between this current coronavirus pandemic and the global spanish influenza pandemic of years ago, but the concept of managing comorbidities, other than post-war malnutrition, would not have been foremost in mind at that time. diabetes was, however, very much a consideration with the swine flu pandemic of , when contingency planning and management guidelines were issued. , even then it was recognised that people with diabetes were potentially six times more likely to require hospitalisation during an influenza epidemic. however, circumstances are different now, with no natural innate covid- immunity in the population and a preventative vaccination programme yet to be developed. recognising that some people may be more seriously vulnerable to infection, the uk government identified certain groups, primarily those with potential immune deficiency or with severe respiratory conditions, and advised that they self-isolate at home for weeks. although diabetes was not included in this list, people with diabetes have nonetheless been encouraged to take particular care with precautionary measures such as social distancing and relative self-isolation. the principles of diabetes management with infection remain relevant ('sick-day rules'). under these circumstances people with diabetes may well feel anxious, with concerns about their diabetes control, availability of medical supplies and their access to expert advice. guidance for people with diabetes has been made available online from organisations such as diabetes uk and jdrf, and similarly for health care professionals from specialist bodies including the association of british clinical diabetologists, the us endocrine society jointly with the university of leeds, and an international perspective from the national diabetes foundation of india. the latest ( march ) clinical guide for the management of people with diabetes during the coronavirus pandemic has been issued jointly from the royal college of physicians, abcd and the nhs, while a national diabetes inpatient covid response team has provided advice on maintaining essential elements of the diabetes service, and collating shared experience to learn from these unprecedented circumstances. education programmes in self-management, especially what to do in the event of acute illness, should be returning the desired dividend, but specialist advice must continue to be available for people in difficulties with their diabetes control. for instance, immediate facility will need to be in place to initiate insulin therapy for those with type diabetes previously bordering on the edge of acceptable control on maximum oral hypoglycaemic agents. with the swine flu pandemic a five-to -fold increase in new case insulin demand was anticipated, and it has to be assumed the same need will arise with this pandemic; important data to be analysed in due course. at the time of writing, the peak rate of those infected, the numbers hospitalised and sadly the case-fatalities in the uk has yet to be reached, with measures still in place to suppress virus transmission and lessen pressures on the nhs. inevitably, questions concerning easing of current restrictions raise issues as to whether there is sufficient acquired immunity in the population -present indication is that still is a low proportion -or whether that can only be achieved once an effective vaccination programme has been developed. it is possible that countries where a speedier response was initiated at the outset of the epidemic, have been in a better position to see restrictions lifted. having gained previous experience with the former sars-cov and mers-cov coronavirus pandemics, singapore has been cited as an exemplary model of management, being wellprepared in terms of pre-planning and rapid implementation of control measures, quarantining of infected individuals and family, along with early school closure and workplace distancing. based on personal observation, as a visitor at the time, everyone on airport arrival and at entry to public buildings, was subject to infra-red thermal scanning and if febrile, individuals were immediately isolated with rigorous contact tracing. seemingly an effective measure -was this a missed opportunity in the uk? furthermore, the addition of extensive antigen testing for infected persons and in particular of asymptomatic contacts appeared crucial to early success in controlling the outbreak, thereby facilitating an earlier return to post-epidemic normality, albeit with a small secondary wave relapse attributed to returning nationals, since similarly reported in china. at present uncertainty prevails, particularly for those in recognised vulnerable groups, such as diabetes. without a reliable antibody test, many if not most people will be unsure as to their immune status, and indeed for those who have recovered from overt coronavirus infection, the degree and duration of immunity to further infection are uncertain. as yet, no specific data in respect of diabetes are available. will the immune response to infection be different with diabetes? so many questions are at present waiting to be addressed. with diabetes itself being a potential composite comorbidity, to what extent is outcome determined by additional renal and cardiovascular considerations? how have differing levels of glycaemic control and medication influenced outcome? were drugs such as metformin and sglt inhibitors discontinued on hospitalisation as advised and, if so, with what consequence? what proportion of patients needed immediate conversion to insulin? did statins improve the anti-inflammatory response or, like non-steroidals, possibly the reverse? did ace inhibitors adversely affect outcome or not? the answers will be awaited with considerable interest. meanwhile, as the pandemic takes its course, the focus moves towards an exit strategy from current restrictions, so far untested and almost impossible to configure without risking infection for those as yet unaffected by illness. by having taken extra precaution with those most vulnerable including diabetes, these individuals remain at risk, requiring a level of continued care probably until a safe and effective vaccine becomes available. suggestions have been mooted of a differential phased release, but there is no easy answer, and much will be learnt from the experience. this pandemic will eventually settle, but it is unlikely to be the last. knowledge gained should be used to prepare well in advance for such future contingency and, as ever, the extra burden of diabetes in the event of overwhelming contagious disease must be constantly addressed. infection and diabetes impaired leukocyte function in patients with poorly controlled diabetes commentary: covid- in patients with diabetes coronavirus and diabetes: an update clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centred, retrospective, observational study clinical characteristics of coronavirus disease in china characteristics of and public health responses to the coronavirus disease outbreak in china diabetes is a risk factor for the progression and prognosis of covid- clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china. intensive care med prevalence and impact of diabetes among people infected with sars-cov- preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states deaths involving covid- , england and wales clinical characteristics of covid- in new york city pandemic influenza -surge capacity and prioritisation. final guidance preparations for pandemic influenza (diabetes) effectiveness of influenza vaccine in reducing hospital admission in people with diabetes our response to covid- as endocrinologists and diabetologists clinical considerations for patients with diabetes in times of covid- epidemic publications approval reference . nhs england, royal college of physicians, and the association of british clinical diabetologists letter to health care professionals from the national diabetes inpatient covid response team interventions to mitigate early spread of sars-cov- in singapore: a modelling study key: cord- -l ioyhur authors: scherbaum, werner a. title: diabetes update : das wichtigste für die ärztliche praxis date: - - journal: diabetologe doi: . /s - - - sha: doc_id: cord_uid: l ioyhur at the virtual event diabetes update , numerous new findings and recommendations on diagnosis, therapy and management of diabetes and related topics were presented, of which the topics type diabetes, diabetes and heart, diabetes and pregnancy as well as vaccinations are described in detail in separate articles in the current issue of der diabetologe. in the following, the most important and, from the author’s point of view, most relevant news from the other diabetes-related subject areas are briefly presented. in der direct-studie wurde bei insgesamt patienten/innen mit typ- -diabetes in hausärztlichen praxen in nordengland und schottland geprüft, inwieweit durch ein gewichtsmanagementprogramm eine starke gewichtsreduktion und eine diabetesremission erreicht werden können. teilnehmer/ innen der interventionsgruppe erhielten u. a. einen mahlzeitenersatz durch eine flüssige formuladiät von - kcal pro tag über - monate; danach wurde stufenweise wieder eine normalkost eingeführt. die kontrollgruppe wurde mit einer leitlinienorientierten standardtherapie versorgt. in der interventionsgruppe wurden die antidiabetische und die antihypertensive therapie schon zu studienbeginn abgesetzt. nach monaten hatten % der teilnehmer/innen der interventionsgruppe, aber keiner in der kontrollgruppe eine gewichtsabnahme von mindestens kg erreicht. eine diabetesremission (definiert durch einen hba c-wert von weniger als , %) wurde bei % der teilnehmer/innen der interventionsgruppe, aber nur % der kontrollgruppe erzielt. die publizierten -jahres-ergebnisse der studie ergaben nun, dass eine remission des diabetes immer noch bei mehr als / der teilnehmer/innen der interventionsgruppe, aber nur bei % der kontrollgruppe vorlag. erwartungsgemäß war die chance für eine diabetesremission umso höher, je stärker die gewichtsreduktion ausgeprägt war. Über die reduktion der täglich zugeführten kalorien hinaus spielt die zusammensetzung der mahlzeiten für den erfolg einer gewichtsverminderung bei adipositas und t d eine wesentliche rolle. das zeigte auch eine kürzlich publizierte dänische studie, bei der personen mit typ- -diabetes über wochen hinweg entweder mit einer kohlenhydratarmen diät mit % kohlenhydraten und einer entsprechenden erhöhung des fettgehalts auf % oder einer isokalorischen kost mit % kohlenhydraten und % fett ernährt worden waren und danach über wochen hinweg die andere kost zuführten. im vergleich zu der gruppe mit konventioneller ernährung kam es in der gruppe mit kohlenhydratarmer diät zu einem signifikant stärkeren abfall des hba c-werts und der nüchternglukosekonzen-tration sowie auch des postprandialen glukoseanstiegs, des leber-und des pankreasfettgehalts [ ]. im gegensatz zu den klassischen ernährungsempfehlungen für patienten/innen mit typ- -diabetes von mahlzeiten pro tag ergab eine neue studie, dass menschen mit t d von einer beschränkung auf mahlzeiten pro tag profitieren. die zufuhr von mahlzeiten pro tag führte im vergleich zu einer isokalorischen zufuhr von mahlzeiten pro tag . dies ist eine ausge-sprochen positive entwicklung. in einer weiteren arbeit der dpv-initiative wurde gezeigt, dass bei insgesamt patienten/innen mit t d, jünger als jahre (medianes alter: jahre), mit einer diabetesdauer von mehr als jahr (im mittel: , jahre), die hba c-werte in den ersten monaten nach beginn der cgm im vergleich zu den ausgangswerten hochsignifikant niedriger waren und dass die häufigkeit der diabetischen ketoazidose unter anwendung der cgm binnen - monaten signifikant abnahm [ ] . schließlich wurde in einer zusammenarbeit der deutsch/österreichischen dpv-gruppe und einem australischen konsortium (wacdd) nachgewiesen, dass bei kindern mit einer manifestation des t d vor dem . lebensjahr (daten von - ) der mittlere hba c von , auf , % (dpv) bzw. von , auf , % (wacdd) reduziert wurde und gleichzeitig die rate an schweren hypoglykämien jährlich um % (dpv) bzw. % (wacdd) abnahm ([ ]; . abb. ). dies zeigt, dass -im gegensatz zu der altbekannten botschaft aus der dcct -bei einer strukturierten diabetestherapie mit anwendung der neuen technologien ein besserer hba c-zielwert bei t d nicht generell mit einer erhöhung des hypoglykämierisikos einhergeht. die alltagstauglichkeit eines modernen closed-loop-systems wurde in einer multizentrischen studie aus den usa belegt, in der patienten/innen mit t d (alter: - jahre, hba c: , - , %) randomisiert entweder mit einem closed-loop-system oder mit einer sensorunterstützten pumpentherapie über monate hinweg behandelt wurden. mit dem closed-loop-system stieg die zeit im zielbereich von - mg/dl ( , - mmol/l) von % auf %, während sie in der kontrollgruppe unverändert bei % blieb. auch bezüglich der mittleren glukosekonzentration und des hba c-wertes fand sich ein deutlicher vorteil des closed-loop-systems. episoden von schweren hypoglykämien traten mit beiden systemen nicht auf [ ] . das die ergebnisse neuer studien bestärkten den erfolg intravitrealer anti-vegf-injektionen, insbesondere bei der proliferativen diabetischen retinopathie. hervorzuheben ist dabei ein therapieschema nach dem sog. protokoll s, bei dem erstmals in einer randomisierten studie bei patienten/innen mit pdr der vorteil einer kontinuierlichen repetitiven therapie mit dem anti-vegf ranibizumab gegenüber einer panretinalen lasertherapie ( - sitzungen mit ca. herden) nachgewiesen wurde. in einem follow-up von jahren verbesserte sich der visus in der mit anti-vegf behandelten gruppe im vergleich zur gruppe mit lasertherapie signifikant, und auch die rate der erforderlichen vitrektomien war in ersterer gruppe niedriger [ ] . der vorteil des algorithmus von protokoll s wurde auch in einer aktuellen posthoc-studie bestätigt, wobei es unter einer solchen therapie nach monaten in % der fälle zu einer auflösung der neovaskularisationen kam. die autoren/ innen folgerten aus den ergebnissen dieser studie, dass unter der ivom-therapie mit weniger dme, höherem visus und dauerhaft besserem gesichtsfeld zu rechnen sei [ ] . Ähnlich positive ergebnisse hypertonie · diät, essen und ernährung · adipositas · diabetische angiopathien · migranten/innen diabetes update : the most important points for medical practice abstract at the virtual event diabetes update , numerous new findings and recommendations on diagnosis, therapy and management of diabetes and related topics were presented, of which the topics type diabetes, diabetes and heart, diabetes and pregnancy as well as vaccinations are described in detail in separate articles in the current issue of der diabetologe. in the following, the most important and, from the author's point of view, most relevant news from the other diabetes-related subject areas are briefly presented. hypertension · diet, food, and nutrition · obesity · diabetic angiopathies · migrants abb. reduktion der knochendichte (bmd ["bone mineral density"]) jahr nach bariatrischen operationen, mrybg roux-en-y-magenbypass ("roux en y gastric bypass"), gcp , operative faltenbildung der großen kurvatur mit fixierung der falte ohne resektion von gewebe (["greater curvature plication"], modifikation der sg), sg schlauchmagenanlage ("sleeve gastrectomy"). (aus [ ]) gegenüber einer panretinalen lasertherapie ergaben sich in einer randomisierten kontrollierten phase- b-studie mit dem anti-vegf aflibercept, in welcher ebenfalls eine regression der neovaskularisation nachgewiesen wurde [ ] . abb. behandlung eines chronischen diabetischen fußulkus mit topisch verabreichtem hyperbarem sauerstoff [ ] . mit freundlicher genehmigung von advanced oxygen therapy, inc. knies gingen stark zurück [ ] . in einer studie aus dem südwesten englands wurde gefunden, dass die inzidenz diabetesbedingter majoramputationen der unteren extremität signifikant invers mit der bereitstellung von fußbehandlungseinrichtungen korreliert ist und die einführungen einer entsprechenden infrastruktur innerhalb von jahren zu einer signifikanten reduktion der majoramputationen führte [ ] . im internationalen vergleich sind die amputationsraten der unteren extremitäten in deutschland hoch. in einer kürzlich publizierten populationsbasierten beobachtungsstudie wurden die kompletten nationalen krankenhausentlassungsdaten von - anhand der drg-einträge ausgewertet. dabei ergab sich eine reduktion der zahl der amputationen an den unteren extremitäten, insbesondere von majoramputa-tionen oberhalb des knies, in diesem zeitraum, die bei frauen (- %) deutlich stärker ausgeprägt war als bei männern (- , %). die krankenhaussterblichkeit aller fälle mit amputationen an den unteren extremitäten sank von , % im jahr auf , % in [ ] . dies weist auf eine verbesserung der versorgung von patienten/innen mit einem diabetischen fußsyndrom hin. dennoch liegt die absolute zahl an amputationen in deutschland deutlich höher als in anderen vergleichbaren ländern wie den niederlanden oder in england. entsprechend einer internationalen vergleichsstudie zu amputationen im jahr liegt deutschland mit , majoramputationen pro . personen/ jahr im höchsten viertel; der oecd-durchschnitt beläuft sich auf , majoramputationen pro . einwohner/ jahr [ ] . die ergebnisse einer kürzlich publizierten studie fachten die diskussion um den stellenwert der hyperbaren sauerstofftherapie zur förderung der abheilung diabetischer fußgeschwüre neu an. in der randomisierten doppelblinden plazebokontrollierten (durch scheinanwendung) studie wurde die effektivität einer häuslichen, zyklischen, topischen sauerstoffdrucktherapie zur behandlung von therapierefraktären diabetischen fußulzera untersucht, die unter einer alleinigen standardtherapie nicht zur abheilung gebracht werden konnten. die ergebnisse waren ausgesprochen positiv: nach wochen wurde unter der two -therapie in % der betroffenen eine komplette ulkusheilung erreicht; in der kontrollgruppe waren es nur %. in der mit two behandelten gruppe waren monate nach beginn der studie % der ulzera abgeheilt, in der kontrollgruppe % ( [ ] , . abb. ). der referent wies darauf hin, dass die ergebnisse dieser studie im gegensatz zu bisher publizierten untersuchungen stehen, in welchen kein vorteil einer lokal applizierten sauerstofftherapie festgestellt worden war. er verwies aber auf den beschluss des g-ba, nach dem diabetische fußulzera ab wagner-stadi-um unter bestimmten bedingungen mit hbo behandelt werden dürfen (s. unten). die vorgaben des g-ba zum möglichen einsatz der hbo setzen eine leitliniengerechte therapie in einer für den diabetischen fuß qualifizierten einrichtung und erfolglosigkeit der standardtherapie voraus. der referent betonte, dass es wesentlich kostengünstigere behandlungen des schweren diabetischen fußulkus gibt, deren positive wirkung in mehreren gut kontrollierten studien eindeutig nachgewiesen wurde, wie z. b. den einsatz des "total contact cast", der jedoch in deutschland finanziell nicht vergütet wird. six-month randomized, multicenter trial of closedloop control in type diabetes panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy. a randomized clinical trial rationale and application of the protocol s antivascular endothelial growth factor algorithm for proliferative diabetic retinopathy clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at weeks (clarity): a multicentre, single-blinded, randomised, controlled, phase b, non-inferiority trial association between vessel density and visual acuity in patients with diabetic retinopathy and poorly controlled type diabetes optical coherence tomography angiography versus fluorescein angiography in the diagnosis of ischaemicdiabeticmaculopathy detection of clinically unsuspected retinal neovascularization with wide-field optical coherence tomography angiography a lack of decline in major nontraumatic amputations in texas: contemporary trends, risk factor associations, and impact of revascularization decreasing rates of major lower-extremity amputation in people with diabetes but not in those without: a nationwide study in belgium diabetes-relatedmajorlimbamputationincidence is strongly related to diabetic foot service provision and improves with enhancement of services: peer review of the south-west of england amputation rates of the lower limb by amputation level-observationalstudyusinggermannational hospital discharge data from lowerextremityamputationratesinpeople with diabetes as an indicator of health systems performance. a critical appraisal of data collection - by the organization for economic cooperation and development (oecd) impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia a multinational, multicenter, randomized, doubleblinded, placebo-controlled trial to evaluate the efficacy of cyclical topical wound oxygen therapy (two ) in the management of chronic diabetic foot ulcers: the two study beschluß des gemeinsamen bundesausschusses über eine Änderung der richtlinie methoden vertragsärztlicher versorgung. hyperbare sauerstofftherapie bei diabetischem fußsyndrom. beschlußdatum: . . cardiovascular events and mortality in white coat hypertension: a systematic review and metaanalysis nondipping nocturnal blood pressure predicts sleep apnea in patients with hypertension bedtime hypertension treatment improves cardiovascular risk reduction: the hygia chronotherapytrial are patients with hypertension and diabetes mellitus at increased risk for covid- infection? covid- and the cardiovascular system renin-angiotensin-aldosterone system inhibitors in patients with covid- cardiovascular disease, drug therapy, and mortality in covid- renin-angiotensin-aldosterone system blockers and the risk of covid- renin-angiotensin-aldosteronesysteminhibitors and risk of covid- prevalence of comorbidities and its effects in coronavirus disease patients: a systematic review and metaanalysis diabetes and ramadan: practical guidelines fallstricke in der diabetesdiagnostik: wird zu lax mit den laborwerten umgegangen preventing misdiagnosis of diabetes in the elderly: age-dependent hba c reference intervals derived from two population-based study cohorts progressinautomated urinalysis "severe acute respiratory syndrome coronavirus " sglt natriumabhängiger glukosekotransporter ("sodium dependent glucose transporter") typ- -diabetes typ- -diabetes topische sauerstoffdrucktherapie ("topical wound oxygen") vaskulärer endothelialer wachstumsfaktor ("vascular endothelial growth factor") decreasing trends in mean hba c are not associated with increasing rates of severe hypoglycemia in children: a longitudinal analysis of two contemporary population-based pediatric type diabetes registries from australia, and germany/ austria between and . diabetes care key: cord- -d l sbeb authors: oberoi, sumit; kansra, pooja title: economic menace of diabetes in india: a systematic review date: - - journal: int j diabetes dev ctries doi: . /s - - -z sha: doc_id: cord_uid: d l sbeb aim: diabetes mellitus is recognised as a major chronic pandemic disease that does not consider any ethnic and monetary background. there is a dearth of literature on the cost of diabetes in the indian context. therefore, the present study aims to capture the evidence from the literature on the cost of diabetes mellitus in india. methods: an extensive literature was reviewed from academia, ncbi, pubmed, proquest, ebsco, springer, jstor, scopus and google scholar. the eligibility criterion is based on ‘picos’ procedure, and only those studies which are available in the english language, published between and february , indexed in abdc, ebsco, proquest, scopus and peer-reviewed journals are included. results: a total of thirty-two studies were included in the present study. the result indicates that the median direct cost of diabetes was estimated to be ₹ , /- p.a. for the north zone, ₹ , /- p.a. for the south zone, ₹ , /- p.a. for the north-east zone and ₹ /- p.a. for the west zone. similarly, the median indirect cost of diabetes was ₹ , /- p.a. for the north zone, ₹ /- p.a. for the south zone, ₹ , /- p.a. for the north-east and ₹ /- p.a. for the west zone. conclusion: the present study highlighted that diabetes poses a high economic burden on individuals/households. the study directed the need to arrange awareness campaign regarding diabetes and associated risk factors in order to minimise the burden of diabetes. electronic supplementary material: the online version of this article ( . /s - - -z) contains supplementary material, which is available to authorized users. 'diabetes is a metabolic disease characterised by hyperglycemia resulting from defects in insulin secretion, insulin action or both' [ ] . with rising pervasiveness globally, diabetes is conceded as a major chronic pandemic disease which does not consider any ethnic background and monetary levels both in developing and developed economies and has also been designated with the status of 'public health priority' in the majority of the countries [ , ] . individuals with diabetes are more susceptible to develop any of the associated complications, viz. macrovascular or microvascular. as a consequence, people experience frequent and exhaustive confrontation with the health care systems [ ] . the treatment cost for diabetes and its associated complications exert an enormous economic burden both at the household and national levels [ ] [ ] [ ] [ ] [ ] . in a developing nation like india, the majority of diabetes patients experience a substantial cost burden from out-ofpocket (oop). also, the dearth of insurance schemes and policies escalate the cost of diabetes care [ ] . instantaneous urbanisation and socio-economic transitions, viz. rural to urban migration, low exercise regimen, lifestyle disorder, etc., have resulted in an escalation of diabetes prevalence in india over the last couple of decades [ ] [ ] [ ] [ ] [ ] . according to the international diabetes federation [ ] , 'india is the epicentre of diabetes mellitus and it was found that in india had the second-largest populace of million diabetic patients, after china. and the figure is expected to be just double million by '. considering that fact, the epidemiologic transition of diabetes has a colossal economic burden [ ] . the estimated country-level health care expenditure on diabetes mellitus in india after amending purchasing power difference was billion us dollars in , pushing india in fourth place globally after the usa, china and germany. looking at the economic burden, in india, diabetes alone exhausts to % share of an average indian household earning [ ] [ ] [ ] . chronic nature and the rising epidemic of diabetes have everlasting consequences on the nation's economy and health status [ ] . therefore, managing diabetes and its comorbidities is a massive challenge in india due to several issues and stumbling blocks, viz. dearth of awareness regarding diabetes, its risk factors, prevention strategies, health care systems, poverty-stricken economy, non-adherence to medicines, etc. altogether, these issues and problems remarkably contribute to the economic menace of diabetes in india [ ] [ ] [ ] [ ] [ ] . after a perspicuous representation of the economic menace of diabetes in india, policymakers and health experts should provide healthier prospects to enhance the quality of life of millions [ ] . thus, the present study aims at capturing the evidence from the literature on the cost of diabetes mellitus in india, reviewing the materials and methods used to estimate the costs and, lastly, exploring future research area. for the accomplishment of the objective, the paper has been divided into five sections. the 'introduction' section of the study discusses diabetes and its economic burden. the 'materials and methods' section deals with materials and methods applied for data extraction and quality assessment. the 'results' section of the present study reports the results of the study. the 'discussion' section concludes the discussion along with policy implications and limitations. a comprehensive literature review was carried out by following the 'preferred reporting items for systematic reviews and meta-analysis (prisma) guidelines' [ ] . the article suggests a minimum set of guidelines and procedures of writing items to enhance the quality of the systematic review. a search was performed between february and march for the accumulation and review of studies published up to january . [ ] . later, articles were identified to be duplicate and removed immediately. of the total articles, limited studies managed to clear the eligibility criterion based upon the significant elements of the 'patient intervention comparison outcome study (picos)' procedure [ ] . title, abstract and keywords of the remaining studies were assessed to determine their relevance. those articles which have been included (a) were available in english language; (b) were published between and february ; (c) were indexed under abdc, ebsco, proquest and scopus; (d) were under journals that are to be peer-reviewed in nature; (e) highlighted unprecedented research outcomes on costs; and (f) were comprising at least one or more demographic zones. thus, the screening procedure facilitated the selection of articles. majority of research publications were excluded on the grounds if they (a) did not provide the detailed analysis of how costs were estimated; (b) were conference articles or posters; (c) only presented the costs of diabetes prevention; and (d) were published in non-peer-reviewed journals. the exploration includes those articles which highlight the cost burden of diabetes in india. whilst performing the analysis, two interdependent excel spreadsheets were developed for data to be summarised. in the very first spreadsheet, a predefined category was used, viz. publication title/year, study type, location, diabetes type, methodology and findings. relevant information is drawn out and presented in table , highlighting the study characteristics of the included articles. the second excel spreadsheet focuses its attention on the list of technical criteria applied to assess the quality of the articles incorporated in the review process. copious checklist has been put forward for the quality assessment of the included studies and majority of them emphasise on the economic assessment, viz. cost analysis, cost-benefit analysis (cba), health care utility analysis, etc. [ , ] . therefore, the quality indicators developed for the present study were grounded on the criterions suggested by prior literature [ ] [ ] [ ] [ ] . a symbol of (√) yes, (×) no and (±) moderately available was assigned to individual quality indicator. each symbol was allocated with a score of , which leads to a maximum attainable score of for each study reviewed. hence, a complete detailed analysis of the parameters utilised is presented in table . the characteristics of the included thirty-two studies are presented in table were included. the cost of diabetes was estimated from various locations such as the south zone (n = ), followed by the north zone (n = ), the north-east zone (n = ) and the west zone (n = ). a large proportion of studies ( %) were defined under india as a whole. whilst conducting review studies, it is imperative to initially define the type, study interest, sample size, data source and outlook of the study. the included studies majorly focus on type diabetes (n = ), followed by both type and type studies (n = ), studies were identified under type diabetes and only study was acknowledged under gestational/foot ulcer category, whilst the remaining studies did not define any diabetes type (table ). of the total studies, % of studies focus on general costs and the remaining studies emphasise on foot ulcers and others. whilst discussing the cost interests, the complications associated with diabetes were estimated by merely studies and the remaining studies ( %) estimated the diabetes cost without any complications. defining sample size is the utmost priority of the study, studies ( %) of the total studies have properly identified the sample size to be ≤ respondents, only studies specified the population size to be > respondents and studies ( %) did not define or provide the sample size. under the source of the cost data section, studies ( %) retrieved data on cost from the patients themselves; for studies ( %), source of cost data was obtained from medical institutes; and the remaining studies ( %) acquired the data on cost from publications. studies on the economic burden of illness could be done through several perspectives, viz. household, patient, societal and governmental. in the particular study, the patient's perspective was most commonly the research question of the study was mentioned? epidemiological definition such as type of diabetes ( and ) studied was provided? complications associated with diabetes were clearly stated? the location of the study respondent was clearly defined? the sample size of the study was adequate? acknowledged by studies ( %), studies considered societal perspective, followed by government perspective for studies and lastly, household perspective was adopted by studies as highlighted in table . the quality of the included studies is broadly presented in table . for all studies, research questions and findings were discussed and explained in a very well-defined manner. the presentation of the results was completely in synchronisation with the aim and conclusions derived from the reviewed articles. it was found that % ( ) of the studies have comprehensively defined the epidemiological definition such as type of diabetes (type and type ). limitations experienced by the majority of studies that hampered the quality of the reviewed articles were the absence of a broad definition of diabetes and a lack of adequate sample size. a major proportion of studies ( %) did not extensively define diabetes and studies ( %) moderately considered the sample size. for most of the reviewed articles, the sampling technique for data collection was addressed and only study did not define the sampling technique. however, % ( ) of studies lucidly defined the tools and technique employed in the reviewed articles and the remaining studies moderately describe the tools and technique. a majority of studies ( %) have properly classified the cost of diabetes and the remaining studies defined moderately. hence, based on quality index scores, the majority of the studies (n = ) scored ' yes' on a -point scale. interestingly, studies attained a marginally higher score of ' yes' of the total studies as presented in table . the economic burden of diabetes mellitus has led to numerous studies on the cost of illness. the cost exerted by diabetes can be categorised into three groups: direct cost, indirect cost and intangible cost [ , ] . direct cost includes both direct health care costs (diagnosis, treatment, care and prevention) and direct non-health care costs (transport, housekeeping, social service and legal cost) [ , ] . indirect cost includes cost for absenteeism, loss of productivity and disability [ , ] . lastly, intangible costs embrace cost for social isolation and dependence, low socio-economic status, mental health and behavioral disorder and loss of quality of life [ , , ] . all twenty-one reviewed studies put forward data and statistics to evaluate per capita cost of individual/household at zone level and the remaining eleven studies highlighted the cost of diabetes at the national level (table ) . to have a clear insight on cost, the reviewed articles have been categorised into four different zones, viz. north zone, west zone, south zone and north-east zone. were lucidly defined? . cost of diabetes was properly classified? the estimated annual direct cost was ₹ /individual and indirect cost was ₹ , including productivity and income loss through illness. ---- the mean total cost of diabetes in india accounts to ₹ /p.a. the mean direct cost of diabetes was ₹ /-and indirect cost, viz. hospitalisation, was /-p.a. (some regional differences in patterns of expenditure exist, with patients in the west of india likely to spend % more on laboratory fees, check-ups and medicines than any other region.) ---- the mean annual direct cost of treatment was ₹ /and % of amount is spent on drugs and medicines. the mean annual indirect cost of treatment was ₹ /of which . % was wage loss. ---- the total cost for diabetes management was ₹ /p.a. of which ₹ /was direct cost for the treatment of diabetes and ₹ /was spent on indirect cost. the total cost for treatment of diabetes with comorbidities was ₹ /p.a. the direct cost with complications was ₹ /p.a. and indirect cost amounts to be ₹ /p.a. ---- the mean direct cost of diabetes for consultation, lab investigation, medicines etc. was ₹ /monthly, whereas indirect cost for outpatient care was ₹ /monthly and indirect cost for inpatient care was ₹ per month. ---- the total average yearly direct cost was observed to be ₹ /-. however, the mean direct cost for all patients with diabetes was ₹ /p.a. individuals with three or more comorbidities encountered % more cost of care, amounting to ₹ , /annually. [ ] katam et al. the average total direct cost per patient annually was amounted to be ₹ , /-. the highest portion of direct cost was spent on insulin and glucose test strips ( %). ---- [ ] khongrangjem et al. the total median cost of illness per month was ₹ /-. total cost was made up of ₹ /direct cost and ₹ /indirect cost. ---- [ ] kumar et al. the total mean evaluation of annual direct spending on ambulatory diabetes care was ₹ /-. ---- [ ] kumar and mukherjee the total direct expenditure incurred on diabetes was ₹ , /p.a. and total indirect expenditure was ₹ , /p.a. ---- kumpatla et al. the total direct cost estimates without any complication were observed to be ₹ /-. the total cost of expenditure with complication was ₹ , /-. (cost for patients with foot complication was ₹ , /-, also average cost for renal patients under the north zone, studies were included to calculate both direct and indirect costs of diabetes at the individual/household level (fig. ) . the median direct cost of diabetes is estimated to be ₹ , /per annum, ranging from ₹ /to ₹ , , /- [ , , , , , [ ] [ ] [ ] . the most commonly measured costing items under direct cost were expenditure on medicines ( studies), diagnostic expenses ( studies), transportation cost ( study), hospitalisation ( studies) and consultation fee ( studies). the median indirect cost of diabetes for the north zone was evaluated to be ₹ , /per annum, ranging from ₹ / -to ₹ , /- [ , , , ] . for all indirect cost studies, costing items, viz. wage loss and leisure time forgone, were used majorly. south zone includes studies, majorly from karnataka state ( studies), followed by tamil nadu ( studies) and andhra pradesh ( study). the median direct cost was assessed to be ₹ , /per annum (fig. ) , ranging from ₹ /to ₹ , /per annum [ , - , , , , , , ] . direct costing items, viz. medicine cost ( studies), consultation fees ( studies) and hospitalisation ( studies), were used in the reviewed article. the median indirect cost of diabetes was ₹ /per annum, ranging from ₹ /to ₹ /per annum with major cost items such as monitoring cost ( study), absenteeism ( studies) and impairment ( study) [ - , , ] . under the north-east and west zone, only one-one study was observed, to evaluate the direct and indirect cost of author publication year was ₹ , /followed by , /-for cardiovascular disease.) [ ] ramachandran the average inpatient and outpatient cost of diabetes is ₹ /p.a. and ₹ /p.a. ---- [ ] ramachandran et al. the total median direct expenditure on health care was ₹ /p.a. ---- the mean cost per hospitalizations was ₹ /p.a. for diabetes. ---- rayappa et al. the direct annual cost (incl. hospital, test, monitoring etc.) was ₹ , /and indirect annual cost was ₹ /-. the total direct cost (incl. drugs, tests, consultation, hospital, surgery, transport) was ₹ /half yearly. the total direct cost (drugs and medicine) for diabetes patients was ₹ p.m. ---- [ ] thakur et al. the mean annual direct expenditure for diabetes care was ₹ and indirect cost was ₹ . ---- [ ] tharkar et al. the total direct cost for hospitalisation was ₹ , p.a. the total direct cost for hospitalisation with comorbidities was ₹ , /p.a. [ ] tharkar et al. the median annual direct cost associated with diabetes care was ₹ , and indirect cost was ₹ , respectively. ---- diabetes at the individual/household level [ , ] . the median direct cost of diabetes for north-east was evaluated to be ₹ , /per annum and ₹ /per annum was observed for the west zone (fig. ) . commonly estimated costing items were surgical procedures, expenditure on drugs/medicines, clinical fees, etc. the median indirect cost estimated for the north-east zone was ₹ , /per annum and ₹ /per annum was analysed for the west zone. indirect costing items identified for both reviewed studies were loss of wage, spendings on health class, travelling expenditure and spendings on diet control. lastly, studies were incorporated to estimate the cost of diabetes for india as a whole at the individual/ household level [ , , - , , , , - ] . the median direct cost of diabetes for india as a whole was ₹ /per annum, ranging from ₹ /to ₹ , /per annum. also, the median indirect cost of diabetes at the individual/ household level was estimated to be ₹ /per annum, ranging from ₹ /to ₹ , /annually ( figs. and ). diabetes mellitus is associated with a large number of serious and chronic complications, which act as a major cause of hospitalisation, morbidity and premature mortality in diabetic patients [ , , , ] . diabetes mellitus is commonly associated with chronic complications both macrovascular and microvascular origin [ , ] . microvascular complications of diabetes mellitus include retinopathy, autonomic neuropathy, peripheral neuropathy and nephropathy [ , ] . the macrovascular complication of diabetes mellitus broadly includes coronary and peripheral arterial disease [ , ] . of the total reviewed studies, only studies estimated the cost of complications associated with diabetes (table ) . a couple of studies on diabetes assessed the cost of illness to be . times higher for individuals with complications as exhibited in table [ , ] . a similar study by sachidananda et al. [ ] concluded that the cost of diabetes is . times higher for complicated non-hospitalised patients and . times higher for complicated hospitalised patients. kapur [ ] inferred that individuals with three or more comorbidities encounter % more cost of care, amounting to ₹ , /annually. according to cavanagh et al. [ ] , india is the most expensive country for a patient with a complex diabetic foot ulcer, where . months of income was required to pay for treatment. three reviewed studies incorporated in the study estimated the cost of individual/household with both macrovascular and microvascular complications [ , , ] kansra [ ] , as suggested by moher et al. [ ] the cost of illness prompted by renal (kidney) complication [ , ] . lastly, eshwari et al. [ ] estimated the total cost for the treatment of diabetes with comorbidities was ₹ /annually. direct cost with complications was ₹ /per annum and indirect cost amounts to be ₹ /annually. rising menace of diabetes has been a major concern for india. with a frightening increase in population with diabetes, india is soon going to be crowned as 'diabetes capital' of the world. a swift cultural and social alteration, viz. rising age, diet modification, rapid urbanisation, lack of regular exercise regimen, obesity and a sedentary lifestyle, will result in the continuous incidence of diabetes in india. the primary objective of this article is to detect and capture the evidence from published literature on the per capita cost at the individual/household level for both direct and indirect costs of diabetes in india which are available and published since . of the total records, studies were identified to meet the inclusion criterion. therefore, the findings of the present study suggest that per annum median direct and indirect cost of diabetes at the individual/household level is very colossal in india. a large proportion of health care cost is confronted by the patients themselves, which affects the fulfilment of health care because of financial restraints [ ] . the proportion of public health expenditure by the indian government is the lowest in the world. as a consequence, out-of-pocket (oop) spending constitutes to be % of the total health expenditure. hence, financing and delivering health care facilities in india is majorly catered by the private sector for more than % of diseases in both rural and urban areas [ ] . direct cost items (expenditure on medicines, diagnostic expenses, transportation cost, hospitalisation and consultation fee) and indirect cost items (loss of wage, spendings on health class and travelling expenditure) were most commonly reported costing items in the present study [ , , , , , ] . most of the reviewed studies on the cost of diabetes highlighted expenditure on drugs/medicine as the foremost costing item which accounts for a significant share of all direct costs. the finding of the present study is consistent with yesudian et al. [ ] , 'cost on drugs constitutes % of the total direct costs'. the majority of the reviewed articles included in the study justify that the primary cause for such abnormal costs of medicines is the common practice adopted by physicians to prescribe brandnamed medicines, rather than generic medicines. in context to the quality of tools and techniques incorporated by the included studies, a large number of articles ( %) witnessed to acknowledge the standards of tools and techniques. similarly, the classification of the cost of diabetes was also determined by the majority of reviewed articles ( articles) . but the absence of a comprehensive definition of diabetes and a small size of individuals/ households produce dubiousness about the standards or quality of the study. hence, the limitations experienced by the majority of reviewed articles hampered the quality of the present study. thus, it is beneficial to develop and suggest standard procedures and framework to conduct a comprehensive and exhaustive study on the cost of diabetes. the present study holds few limitations. primarily the exclusion of the relevant articles presented as conference papers and those studies published under nonpeer-reviewed journals. with the omission of the above literature, some biasness might have been introduced into the review process. furthermore, the major limitation of the present study is the non-availability of published articles under the central and east zone of india. also, the studies published under the north-east zone and west zone were only one. lastly, the heterogeneity in material and methodology used in cost estimation are not analogous. as a consequence, conducting a metaanalysis is not feasible. the above discussion highlighted a huge economic burden of diabetes in india and variations were recorded in the different zones. it was observed that the cost of drugs/medicines accounts for a major burden of the cost of diabetes. the study suggested few policy interventions to cope with the high economic burden of diabetes. there is a dire need in the country to arrange awareness programmes on diabetes and associated risk factors. the menace of diabetes can be controlled by devising new health care policies, introducing new generic medicines and taxing alcohol/tobacco. diabetes is a lifestyle disease so along with the above measures, a change in dietary habits, physical activity, beliefs and behavior can reduce its economic burden. conflict of interest the authors declare that they have no conflict of interest. ethical approval the study is a review-based study, so it does not contain any studies with animals. the present study only reviews those studies which contain individual's performance. informed consent for the present study, it is not necessary to obtain any consent. diagnosis and classification of diabetes mellitus the costs of treating long term diabetic complications in a developing country: a study from india diabetes mellitus and its 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published maps and institutional affiliations key: cord- -jud xc authors: garcía-villasante, eilhart; baca-carrasco, víctor; gutierrez-ortiz, claudia; pinedo-torres, isabel title: diabetes care during covid : experience in telemedicine from a developing country date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: jud xc nan please cite this article as: garcía-villasante e, baca-carrasco ví, gutierrez-ortiz c, pinedo-torres i, diabetes care during covid : experience in telemedicine from a developing country, diabetes & metabolic syndrome: clinical research & reviews ( ), doi: https://doi.org/ . / j.dsx. . . . this is a pdf file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. this version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. dear editor, we have read with interest an article published in this journal ( ) . the authors detail with accuracy the main telemedicine problems and most of them are being seen in our country. we work at endocrinology department in a reference hospital in perú which is in fifth position of confirmed cases of covid worldwide ( ) . our main concern is about diabetic patients because they are at major risk to get infected and develop severe forms of disease ( ). the use of telemedicine in peru is incipient. on march , the peruvian ministry of health stablish the official pathway for its implementation. since then, teleconsultations have been developing slowly and not uniformly in the health centers. according to our national data, almost % of the population belongs to the lowest socioeconomic strata ( ) and they gain less than dollars per month, so many patients do not have smartphones and, if they do, are lacking technology skills. therefore, some of them prefer to speak on regular cellphone line or even on landline which make difficult to see patients' expressions and use non-verbal communication. on this last point, gestures are a basic tool to express very useful thoughts for patients with few language skills or fear and insecurity to express their doubts. this aspect of communication can also be ignored in the different platforms used for teleconsultations, so health professionals should be trained in compensatory strategies to overcome the physical distance ( ). also, in the publication is not been considered the importance of the health institution creating systems for the safe delivery of medications avoiding covid- infection. we coordinate with the insurance office and pharmacy department so that a family member can approach to receive the medications. currently, we have a project in place to decentralize the delivery of medications to primary care centers where viral load by covid is lower. pitfalls in telemedicine consultations in the era of covid and how to avoid them reported cases and deaths by country, territory, or conveyance risk factors for mortality in patients with coronavirus disease (covid- ) infection: a systematic review and meta-analysis of observational studies. the aging male. available at: taylor & francis online informe técnico: evolución de la pobreza monetaria j o u r n a l p r e -p r o o f the authors declare no conflict of interest in this publication. key: cord- -dzm xi authors: filardi, tiziana; varì, rosaria; ferretti, elisabetta; zicari, alessandra; morano, susanna; santangelo, carmela title: curcumin: could this compound be useful in pregnancy and pregnancy-related complications? date: - - journal: nutrients doi: . /nu sha: doc_id: cord_uid: dzm xi curcumin, the main polyphenol contained in turmeric root (curcuma longa), has played a significant role in medicine for centuries. the growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. the pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. in spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. it is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. the reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (gdm), preeclampsia (pe), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. the current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes. maternal nutrition is an essential and modifiable environmental factor that deeply influences maternal and offspring health in the short and long-term [ ] [ ] [ ] [ ] [ ] [ ] . genetics, nutrition, and other environmental factors significantly contribute to the physiological immune and metabolic modifications occurring in pregnancy, to favor maternal adaptation to the growing and developing fetus. maternal malnutrition adversely affects these dynamic processes by acting on the mechanisms related to the nutritional programming, including nutrition sensing signals, epigenetic regulation, gut microbiome, as well as on the nutrient-nutrient and nutrient-drug interactions, modulating maternal and fetal genes in a sex-specific manner [ , [ ] [ ] [ ] [ ] . bw/day of curcumin as a food additive [ ] . however, despite its potential therapeutic benefits, curcumin is poorly bioavailable due to its rapid metabolism, and the small portion of substance that is absorbed is extensively bio-transformed into its water-soluble metabolites, glucuronides, and sulfates [ ] . therefore, several strategies have been developed to enhance its bioavailability and efficacy, to increase oral and gastro-intestinal absorption, and to reduce the clearance from the body [ ] [ ] [ ] . for this purpose, taking into consideration that curcumin is fat-soluble, several delivery systems have been developed to obtain a number of formulations by mixing curcumin with different materials, including adjuvants, such as piperine [ , ] . micelles, liposomes, phospholipid complexes, phytosomes, emulsions, microemulsions, nano-emulsions, solid lipid nanoparticles, nanostructured lipid carriers, biopolymer nanoparticles, and microgels represent different and recent technical approaches to encapsulate curcumin [ ] [ ] [ ] , although further studies are needed to evaluate their effectiveness and safety as potential health-promoting compounds in humans. it is well known that dynamic changes in insulin sensitivity take place during healthy pregnancy to allow adequate supply to the growing fetus [ ] . in pregnancy, several players, including hormones, cytokines, and metabolic factors, contribute to the development of insulin resistance through complex mechanisms, not yet completely understood [ , ] . maternal obesity, related to unhealthy diet and lifestyle, can negatively affect insulin sensitivity leading to the development of gdm and type diabetes (t d), with serious short and long-term health consequences for both the mother and the offspring [ , ] . recent evidence emphasized the anti-hyperglycemic activity of curcumin, both in animals and humans [ ] . specifically, this compound had the capability to improve glucose uptake, insulin sensitivity, and pancreatic β-cell function, as well as liver and kidney function, and to reduce glucose and lipid levels, oxidative stress, and inflammation [ ] , by interacting with almost all the players involved in these processes, as demonstrated in in vitro studies [ , ] . as regards human studies, the effects of curcumin supplementation have been evaluated in several randomized controlled trials. a recent intervention study showed that mg/day curcumin supplementation ( mg capsules: mg of curcumin, mg of demethoxycurcumin, and mg of bisdemethoxycurcumin) for weeks reduced triglycerides (tg) and c-reactive protein (crp), and increased adiponectin levels [ ] , whereas mg/day curcumin co-administered with piperine mg/day for three months was able to reduce blood glucose, c-peptide, glycated hemoglobin (hba c), alanine aminotransferase (alt) and aspartate aminotransferase (ast), in patients with t d [ ] . another study showed that the daily ingestion of mg turmeric powder for eight weeks resulted in a reduction in body weight, low density lipoprotein-cholesterol (ldl-c), and tg levels, with no significant effects on glycemia, crp, and hba c, in hyperlipidemic t d patients [ ] . in obese women with polycystic ovary syndrome (pcos), mg/day curcumin supplementation ( mg twice daily: - % curcumin, - % demethoxycurcumin and . - . % bisdemethoxycurcumin) for six weeks improved serum insulin and the quantitative insulin sensitivity check index [ ] . a recent meta-analysis reported that curcumin intake was associated with reduced body mass index (bmi), body weight, body fat, leptin value, and increased adiponectin levels in patients with metabolic syndrome and related disorders [ ] . overall, the dosage and duration of curcumin supplementation appear to differently modulate glucose metabolism in humans. a recent promising approach to treat hyperglycemia consists of combining the effects of curcumin and the ongoing antidiabetic agents, as observed in diabetic rats treated with a combination of curcumin and metformin. specifically, this association improved hyperglycemia, dyslipidemia, and oxidative stress, increasing the activity of the antioxidant enzyme paraoxonase (pon ), in diabetic rats [ ] . dietary bioactive compounds might have beneficial effects on gdm [ , ] . in particular, curcumin appeared to improve gdm and gdm-related complications in a recent study in a mouse model. specifically, c bl/ksjdb/+ diabetic pregnant mice were supplemented with different curcumin dosages: mg/kg and mg/kg/day, from gestational day zero (gd ) to gd . results showed that mg/kg curcumin significantly reduced blood glucose and insulin levels, increased hepatic glycogen content, and improved oxidative stress by reducing thiobarbituric acid reactive substance (tbars) and increasing glutathione (gsh) levels, superoxide dismutase (sod), and catalase (cat) activities in the liver of diabetic pregnant mice at gestational day . the reduced ' adenosine monophosphate-activated protein kinase (ampk) and increased histone deacetylase hdac activities observed in gdm liver were reverted by curcumin treatment. furthermore, curcumin positively influenced the offspring of mothers with gdm, restoring litter size and birth weight, and inducing the reduction of glucose- -phosphatase (g pase) expression and activity in the liver [ ] ( table ) . congenital birth defects, including neural tube defects (ntd), occur more often in the offspring of diabetic mothers. in a recent study, mouse embryos (at e . of development) were cultured for h with mg/dl glucose, in the absence or presence of curcumin ( and µm). remarkably, µm curcumin was able to reduce the rate of embryos with ntd induced by high glucose. curcumin reduced high glucose-induced oxidative and nitrosative stress [i.e., decreased -hydroxynonenal ( -hne), nitrotyrosine levels, and lipid hydroperoxide (lpo)], as well as endoplasmic reticulum (er) stress (i.e., decreased expression of er-markers stress such as phosphorylated protein kinase-like endoplasmic reticulum kinase (p-perk), phosphorylated inositol-requiring protein- α (p-ire α), phosphorylated eukaryotic initiation factor α (p-eif α), c/ebp-homologous protein (chop), binding immunoglobulin protein (bip), and x-box binding protein (xbp ). moreover, µm curcumin inhibited the cleavage of pro-apoptotic caspases (i.e., casp- and - ) [ ] . although the results from preclinical studies are overall promising, further research is needed to better understand the molecular mechanisms underlying diabetic complications, as well as the pharmacodynamics and pharmacokinetics of curcumin in pregnancy, to conceivably employ this compound as a therapeutic agent for human pregnancy complications. critical changes in the cardiovascular system occur in physiological pregnancy, to ensure maternal and fetal adaptation to the increased metabolic demand and to guarantee adequate uteroplacental circulation for fetal growth. a healthy pregnancy is hallmarked by systemic vasodilatation, significantly related to the high levels of estrogen and progesterone. cardiac output and heart rate rise during gestation and the activation of the renin-angiotensin-aldosterone system leads to a significant increase in total blood volume. alterations in these processes are associated with maternal and fetal morbidity and mortality [ ] . obesity, older maternal age, and diabetes mellitus increase the risk of cardiovascular diseases in pregnancy ( - %), with a higher prevalence when including hypertensive disorders-chronic hypertension, pregnancy-induced hypertension, pre-eclampsia, and hellp syndrome (hemolysis, elevated liver enzymes, and low platelet count) [ ] . considering the anti-inflammatory, antioxidant, and antiangiogenic activities observed in several studies, curcumin is a potential therapeutic compound in cardiovascular disorders [ ] . preeclampsia (pe) is a systemic syndrome characterized by hypertension and proteinuria, which begins after weeks of gestation; it occurs in - % of pregnancies, and it is a leading cause of maternal and fetal morbidity and mortality [ ] . although the pathophysiology of pe remains to be elucidated, alterations in maternal vascular physiology have been described, leading to a generalized vasoconstrictive state, systemic oxidative stress, inflammation, and endothelial cell dysfunction, with severe adverse effects on the placenta, one of the major organs that develops after conception [ , ] . strategies to reverse or arrest the pathological processes of pe are aimed at reducing excessive inflammatory response, micro-emboli formation, and vasoconstriction by using specific drugs or natural products [ ] . for this purpose, studies in animal models have been performed. it has been observed that in lipopolysaccharides (lps)-treated pregnant rats to create a pe model (lps . µg/kg on gestational day ), the administration of curcumin ( . mg/kg, from gd to gd ) improved hypertension, proteinuria, and renal damage, and reduced serum levels of il- and monocyte chemoattractant protein- (mcp- ). curcumin treatment ameliorated inadequate trophoblast invasion and spiral artery remodeling, significant histopathological alterations observed in pe. analysis of placental tissue showed that curcumin administration decreased the lps-induced expression of the inflammatory molecules toll-like receptor (tlr)- , il- , and the proinflammatory transcription factor nf-kb. according to the obtained data, the authors hypothesized that curcumin may positively modulate the cascade of different signaling pathways involved in pe development [ ] . similar results were obtained in a mouse model of lps-induced pe. in this study, in addition to blood pressure and proteinuria reduction, curcumin increased the number of live pups, fetal and placental weight, and decreased fetal desorption. these effects were associated with the inhibition of placental expression of tnf-α, il- β, il- cytokines, and mcp- and mip- chemokines, and with a reduction in macrophage infiltration. the reduced inflammatory status was accompanied by increased activation of the serine/threonine-specific protein kinase akt, involved in cellular proliferation [ ] . neo-vascularization is a critical event mediated by several angiogenic factors-including the vascular endothelial growth factor (vegf), fibroblast growth factors (fgfs), matrix metalloproteinases (mmps)-and inflammatory factors such as cyclooxygenase (cox)- and nf-kb, occurring not only in tumor progression but also in early placentation [ , ] . curcumin appears to modulate the above-mentioned factors, influencing vessel formation by acting either as a proangiogenic or as an antiangiogenic molecule, depending on the concentration and the cell type [ ] . a recent study investigated the effect of curcumin in htr /svneo trophoblasts cells, a model of the human first-trimester placenta. incubation with curcumin at low concentration ( - µm for h) stimulated (i) proliferation with concomitant activation of akt, (ii) tube formation of placental trophoblast htr /svneo cells, (iii) and increased the expression of the proangiogenic factors vegf, vegfr , and fabp . in addition, curcumin treatment strongly increased the mrna and protein expression of hla-g, involved in the immune regulation during trophoblast invasion; and mrna expression of a relevant number of genes related to the notch-signaling pathway, which regulates angiogenesis. the authors examined the promoter methylation of genes involved in metabolic and oxidative stress and observed that curcumin induced hypomethylation in genes involved in the protection against oxidative stress and dna damage. altogether these data indicate that curcumin is able to promote angiogenesis and to activate protective pathways in the first trimester of pregnancy, and supports the development of the placental trophoblast [ ] . moreover, htr /svneo trophoblast cells were used to evaluate the protective effects of curcumin against oxidative stress induced by h o ( µm for h). results showed that pretreatment with curcumin ( µm for h) increased cell viability, upregulated the activities of the antioxidant enzymes cat and glutathione peroxidase (gsh-px), reduced the h o -induced ros accumulation and the apoptotic rate. at molecular levels, these data were associated with an increased nuclear translocation of the antioxidant transcription factor nrf , and reduced expression of cleaved-caspase [ ] . the anti-inflammatory activity of curcumin has been also observed in vitro in human gestational tissues treated with lps. specifically, incubation with curcumin ( µm for h) reduced il- release, and il- and il- mrna expression induced by lps, in both placenta and fetal membranes. moreover, curcumin decreased placental cox- mrna expression, prostaglandin pge and pgf a release, and the expression and activity of the matrix-degrading enzyme mmp- , in association with reduced activation of nf-kb [ ] . although several clinical trials emphasized the benefits of curcumin in different pathological contexts [ , , , ] , there are few data on curcumin supplementation in human pregnancy. recently, a double-blind randomized clinical trial involving pregnant women with preeclampsia was conducted to evaluate the possible effect of curcumin on the expression of cox- and il- , thought to have a role in the pathogenesis of pe. the enrolled patients were randomized to receive either curcumin mg/d (n = ) or placebo (n = ) [ ] . the authors analyzed the circulating levels of il- and cox- , at t , min after curcumin ingestion, and h after delivery. results showed that curcumin did not modify the expression of the analyzed molecules at any tested time. the authors hypothesized that the absence of effect might be due to the low dose of curcumin, taking into account that in non-pregnant subjects doses can reach more than g/day [ ] . during the antenatal and postpartum periods, women are particularly prone to develop mental disorders, including depression. postpartum depression (ppd) occurs in - % of women, leading to significant health consequences for both mother and offspring [ ] . this condition has been largely underestimated and understudied so far. hence, its prevalence is supposed to be higher, conceivably reaching % of women. symptoms of depression begin during pregnancy in about % of women and numerous environmental, genetic, biochemical, and epigenetic factors likely contribute to the onset of ppd [ ] [ ] [ ] , although the exact mechanisms responsible for this condition are not yet completely known. several pharmacological and psychological approaches are currently adopted to treat ppd, even though complementary and alternative medicine have also been taken into consideration. increasing data have suggested the neuroprotective roles of a healthy diet, rich in fruit and vegetables, highlighting its positive influence on mental health [ ] . on the contrary, an unhealthy dietary pattern increases the risk of systemic low-grade inflammation and neuroinflammation, known to be associated with ppd [ ] . the neuroprotective and antidepressant benefits of curcumin have been known for a long time [ ] [ ] [ ] . several preclinical studies have suggested potential positive effects of curcumin in treating neurological disorders, such as alzheimer's disease, parkinson's disease, multiple sclerosis, migraine, epilepsy, brain and spinal cord injury, and depression [ , , ] . lopresti and colleagues have investigated the effects of curcumin on depression outcomes in humans. they observed that eight-week curcumin supplementation ( mg twice a day) in subjects with major depressive disorder (mdd) was effective in reducing depressive and anxiety symptoms, as demonstrated by the reduction in total depressive symptoms (total ids score), mood/cognitive depressive symptoms (idsm), arousal-related symptoms (idsa), and trait anxiety (stait) [ ] . this supplementation resulted in an increase in urinary levels of both the arachidonic acid metabolite thromboxane b (tbx-b ) and the neuropeptide substance p (sub-p), potentially involved in depression mechanisms. moreover, although curcumin did not modify plasma levels of endothelin- and leptin, a greater antidepressant benefit was observed in subjects with the highest baseline levels of these molecules. the authors hypothesized that curcumin might act by increasing endothelin and leptin receptor activities [ ] . similarly, in another trial, mg/day curcumin ingestion for six weeks or the administration of the antidepressant drug fluoxetine showed comparable efficacy in subjects with mdd [ ] . a recent meta-analysis provided relevant information about curcumin use in depression. specifically, this analysis revealed that curcumin administration (i) appears to be more effective in reducing depression symptoms at a higher dosage ( g/day) and for six weeks or more; (ii) can enhance the action of antidepressants; and (iii) has more effects on subjects with major depression and without other comorbidities [ ] . these results indicate the need for further study to better comprehend the mechanisms of action of curcumin in depression treatment. data obtained from animal and in vitro studies have indicated that curcumin might exert antidepressant activity by acting on different signaling pathways involved in mental disorders. specifically, this compound is able to ameliorate the hypothalamic-pituitary-adrenal (hpa) axis disturbances [ ] . curcumin can influence the unbalanced release of monoamine neurotransmitterssuch as serotonin ( -ht), dopamine (da), noradrenaline, and glutamate-the expression of monoamine oxidase (mao), the expression of neurotrophic factors such as brain-derived neurotrophic factor (bdnf) and neurogenesis, as well as the dysregulated immune system function and oxidative and nitrosative stress. thus, curcumin appears to promote neurogenesis and inhibit neuronal cell apoptosis [ , , , ] . despite the consistent evidence of efficacy and safety of curcumin treatment in other pathological conditions, to date, data on its effects on depression in pregnancy are completely lacking. however, in the last years, there has been a growing awareness of the possible role of anti-inflammatory micronutrients in improving ppd symptoms [ ] . according to the theory of the fetal origin of adult diseases (foad) hypothesized by david barker, the intrauterine environment has a relevant role in fetal growth and development and influences disease susceptibility in the offspring in the short and long term [ ] . the physiological processes of pregnancy require immune and metabolic modifications to accommodate the growing fetus; maternal malnutrition negatively influences this dynamic equilibrium, leading to tissue-specific impairment, with serious adverse outcomes for both mother and child [ , ] . taking into consideration the importance of nutrition in human development, there is a need for better understanding the nutritional programming and the related mechanisms and players acting during pregnancy. the placenta has the fundamental role of transferring nutrients to the fetus, and alterations in placental function have severe effects on fetal growth. placental insufficiency is the most common cause of fetal growth restriction (fgr), a serious condition that affects - % of all newborns [ ] . although the pathophysiology of fgr is not completely known, excessive oxidative stress and inflammation, as well as the activation of a complex network of several signaling pathways, appear to be involved [ , ] . the antioxidant and anti-inflammatory effects exerted by curcumin on the placenta [ ] were confirmed in a mouse model of fgr fed with a low-protein (lp) diet [ ] . the authors showed that maternal supplementation with curcumin ( mg/kg day, from . to . gd) induced a potent antioxidant response in lp-fed pregnant mice; specifically, curcumin (i) increased gsh-px activity, nfr mrna expression, and the blood sinusoids area; (ii) reduced malondialdehyde (mda) content and apoptosis in the placenta, leading to increased placental efficiency; and (iii) elevated the expression of the antioxidant genes sod , sod , and cat, and protein expression of nrf and eme oxygenase- (ho- ) in the liver. overall, curcumin supplementation during pregnancy was able to revert tissue damage and contrast the decrease in fetal weight induced by a lp diet [ ] . curcumin appeared to improve birth weight, inflammation, and oxidative damage also in fgr newborn rats. indeed, fgr rats supplemented with mg/kg curcumin (at six weeks of age for six weeks) displayed reduced levels of the inflammatory cytokines tnf-α, il- β, and il- , reduced activity of ast, alt, and mda enzymes, and increased gpx and gsh activity in serum. antioxidant defense in the liver was significantly improved as well. the attenuation of the inflammatory status induced by curcumin was associated with (i) reduced activation of nf-kb and jak ; (ii) increased expression of the antioxidant genes (nqo , hmox , gst, gpx , and sod ), and activation of their regulatory transcription factor nfr , in the liver [ ] . successively, the same authors investigated the effects of curcumin on insulin resistance (ir) and hepatic lipid accumulation in fgr newborn rats. specifically, supplementation with mg/kg curcumin (at six weeks of age for six weeks) attenuated ir by reducing serum insulin, glycemia, and homeostasis model assessment of insulin resistance (homa-ir). furthermore, in the liver, curcumin diminished total cholesterol, tg, and non-esterified fatty acids (nefa); increased glycogen concentration and induced the activation of lipolytic enzymes, together with a reduction in irs- and akt phosphorylation, a decrease in cd , srebp- , and fasn expression, and an increase in pparα levels. overall, these data showed that curcumin could improve ir and lipid accumulation in the liver by regulating insulin signaling pathways, and promoting lipolysis and fatty acid oxidation in fgr rats [ ] . of note, curcumin alleviated also jejunum damage in fgr growing pigs. indeed, the addition of mg/kg curcumin to diet improved antioxidant defense (i.e., increased sod and decreased mda activity), immune-related gene expression (reduced mrna of tnfα, il- , and ifnγ, and increased il- ), and decreased apoptotic genes, such as caspase and bax in the jejunum. moreover, curcumin supplementation increased mrna expression of the tight junction-related gene ocln [ ] . preterm birth (ptb) is a pregnancy complication that affects about % of births worldwide and is associated with increased maternal and neonate morbidity and mortality [ ] . an altered inflammatory status appears to be associated with ptb. thus the anti-inflammatory activity of curcumin has been evaluated in a mouse model of ptb, obtained through lps injection in the abdominal cavity [ ] . the injection of mg/kg curcumin into the abdominal cavity, one day before (preventative group) or one day after (treatment group) lps treatment, significantly reduced serum levels of tnf-α, il- , and mda, and increased sod levels, in both the experimental conditions, in pregnant mice. the staining intensity of nf-κb p showed that curcumin was able to reduce the lps-induced expression of this inflammatory transcription factor in placental tissue both in the preventative and in the treatment group [ ] . besides maternal nutrition, many other factors, including exposure to chemical and natural toxic agents, drugs, alcohol, smoking, and maternal stress influence fetal growth and development [ ] . among the myriad of properties, curcumin appears to be able to reduce toxicity induced by several environmental agents in different organs and tissues, including the brain and liver [ ] . bisphenol-a (bpa) is a chemical substance adapted to produce plastic. it has been considered an endocrine disruptor by the european chemicals agency (echa ) [ ] due to its estrogenic activity. bpa exposure in pregnancy is associated with negative outcomes, including impaired fetal growth and childhood adiposity [ ] . remarkably, this synthetic compound affected the processes of neurogenesis in the hippocampus of the developing rat brain, and curcumin treatment showed neuroprotective activity by reverting bpa-induced effects. specifically, pups from a pregnant rat receiving bpa ( µg/kg body weight/day from gd to pnd ) were treated with curcumin ( mg/kg body weight/day from pnd to pnd ). the authors performed accurate experiments on embryo and pup brains and examined the expression of genes and pathways involved in neurogenesis. they observed that curcumin attenuated the bpa-induced reduction in neuronal stem cells (nsc) proliferation and differentiation. at molecular levels, the improvement in neurogenesis was associated with the enhanced expression of the proneural transcription factors neurogenin and neurod , the reduced expression of the proapoptotic molecule bax, the increased expression of the antiapoptotic molecule bcl- , and the activation of wnt/βcatenin signaling that regulates nsc proliferation and differentiation. of note, the benefits of curcumin resulted in improved learning and memory in bpa-treated pups [ ] . mercury (hg) is a widely diffused toxic heavy metal that occurs naturally in three forms, namely metallic hg, organic hg, and inorganic hg. human exposure to hg occurs mainly through the environment (e.g., mercury-contaminated sea fish, dental amalgam). of note, occupation (e.g., mining) is another important source of exposure for humans and is associated with possible multi-organ toxicity [ ] . as for the influence of hg on neurodevelopment, a cross-sectional study, involving healthy saudi mothers and their infants (age - months), showed an association between hg exposure and neurodevelopmental delay, with possible negative effects persisting also in adulthood [ ] . interestingly, curcumin appeared to mitigate hg toxicity in animal models [ ] . specifically, pregnant mice were exposed (from gd to pnd) to ppm mercuric chloride (hgcl ) in the presence or absence of and ppm curcumin. hg exposure induced serious damage to the development of neuromotors, and increased anxiety behavior in pups. curcumin administration improved neurodevelopment and reduced anxiety, by restoring the levels of neurotransmitters da, -ht, and acetylcholinesterase (ache), and of the antioxidant gsh, decreased by hg exposure, in forebrain pups [ ] . moreover, by using the same experimental conditions, the authors analyzed changes in body weight, sexual behavior, and fertility in male and female pups. the obtained data showed that curcumin counteracted the perinatal effects of hg exposure by increasing (i) body weight, liver and brain weight in male and female pups; (ii) epididymis, seminal vesicle, testis weight in males; and (iii) ovary weight in females; also sexual behavior was improved in both sexes. moreover, curcumin increased testosterone and fsh levels, and sperm motility in males, as well as fsh, lh, and progesterone in females, reduced by hg exposure [ ] . lead (pb) is a heavy metal widely spread in the environment. it is extremely dangerous for both animals and humans. lead exposure occurs mainly through food and water contamination, and air pollution. lead can cross the placental and blood-brain barrier, inducing neurotoxicity. curcumin exerted neuroprotective effects contrasting lead-induced damage in rats. the concomitant exposure of rat mothers to pb ( g/l) and curcumin ( g/kg) during pregnancy and lactation resulted in the recovery of the pb-induced altered sensorimotor functions in neonatal rats. pb neurotoxicity produced alterations in locomotor neuronal network development and curcumin treatment reversed these anomalies, allowing normal locomotor behavior. these findings indicate that curcumin has the capability to prevent central nervous system dysfunction induced by lead during the earlier stages of development [ ] . celecoxib is a selective inhibitor of cox- that is able to reduce pain and inflammation caused by several inflammatory conditions [ ] . since recent data have shown that the inhibition of cox- reduced adult neural cell proliferation and differentiation [ ] , wang et al., investigated the neuroprotective action of curcumin on fetal brain development in pregnant mice treated with celecoxib [ ] . specifically, pregnant mice were pretreated with curcumin ( nmol/kg body weight) from embryonic day (e) . to e . , and then with celecoxib ( mg/kg body weight) from e . to e . . results showed that curcumin counteracted the celecoxib-induced inhibition of neurogenesis in the fetal frontal cortex, by increasing proliferation and cyclin d expression in neural progenitor cells, and by activating wnt/βcatenin signaling (i.e., decreased expression of glycogen synthase kinase beta (gsk- β), and increased expression of βcatenin) [ ] . valproic acid (vpa), a branched short-chain fatty acid, is an antiepileptic agent that has been associated with congenital malformations, including alterations in fetal brain development, and consequent intellectual disabilities and autistic spectrum disorders in the offspring [ ] . curcumin appears to attenuate the vpa-induced brain damage, as observed in a rodent model of autism. neonatal rats, born to mothers treated with vpa from . gestational day, received a single dose of curcumin ( g/kg day), and their brains were analyzed days after birth. curcumin was able to ameliorate body and brain weight, and the altered expression of il- , ifn-γ, gsh, cyp , in the brain of vpa-exposed pups [ ] . prenatal alcohol exposure (pae) has dramatic effects on fetal growth and development (fetal alcohol spectrum disorders: fasd) and is responsible for neurodevelopmental disorders (i.e., neurocognitive and behavioral deficits, and increased susceptibility to mental health disorders) and birth defects (growth deficits and physical abnormalities). pae induces chromosomal rearrangements and epigenetic alterations, therefore leading to altered gene-environment interactions that are responsible for alcohol-induced disorders [ ] . curcumin ( mg/kg body weight), administered during the peri-adolescence period (pnd - ), appeared to counteract fetal brain damage induced by prenatal and lactational alcohol exposure (plae; % (v/v) alcohol solution) in mice. the authors showed that curcumin improved anxiety and memory deficits caused by plae, and these improvements were associated with reduced microglia activation and astrogliosis. at molecular levels, curcumin reduced protein expression of il- , tnf-α, and nf-kb. these data showed that curcumin may act against cognitive deficits and neuroinflammation induced by alcohol exposure in pregnancy [ ] . curcumin can counteract the deleterious effects of pae on cardiac development, as demonstrated in a mouse model. pregnant mice were daily exposed to ethanol ( % v/v in saline) between embryonic days . to . ; at embryonic day . , mice were euthanized and embryonic hearts were removed. results showed that pae treatment increased apoptosis in pup hearts; this finding was associated with higher levels of caspase- and - mrna expression, and reduced bcl- mrna expression, due to a different modulation of histone h k acetylation near the promoter regions of caspase- , caspase- (hyperacetylation), and bcl- (hypoacetylation). in vitro, curcumin ( µm for h) treatment abolished apoptosis and reverted the expression of caspases and bcl- , induced by alcohol ( mm), in cardiac progenitor cells. these results highlighted the capability of curcumin to prevent congenital heart diseases induced by pae in pregnancy, by acting as an epigenetic modulator [ ] . embryonic development is a complex process that is finely regulated and highly susceptible to environmental influences. therefore, it is reasonable to hypothesize that the anti-inflammatory, antioxidative, antiproliferative, and antiangiogenic properties of curcumin could interfere with the blastocyst stage, implantation and post-implantation development of embryos [ ] . chen and colleagues evaluated the possible embryotoxicity of curcumin in mouse blastocysts both in vitro and in vivo. they observed that curcumin ( µm for h) induced apoptosis in mouse blastocysts, and reduced implantation rate and development, in vitro. then, embryos treated with curcumin were transferred in vivo; results confirmed a significant reduction in implantation ratio, and, among the implanted embryos, a higher rate of failure to develop normally. the authors evaluated the possible mechanisms responsible for these effects and found that curcumin-induced apoptosis was associated with the modulation of pro-and anti-apoptotic molecules (i.e., increased bax and reduced bcl- expression), ros generation, and caspase- activation [ ] . additionally, the same authors showed that curcumin ( µm) adversely affected oocytes maturation, in vitro. this effect resulted in a reduced ability of oocytes to be fertilized, increased blastocyst apoptosis, and reduced blastocyst implantation ratio and development. these results were confirmed in oocytes collected from female mice after feeding them with curcumin supplementation ( µm) for four days [ ] . another in vitro study highlighted that the degree of damage induced by curcumin ( , , or µm curcumin for h) on mouse blastocyst at the implantation stage and during the early post-implantation stage is dose-dependent. specifically, µm and µm curcumin inhibited cell proliferation of the blastocyst but increased the formation of trophoblastic giant cells, whereas µm curcumin exposure was lethal to all blastocysts, and induced severe damage to the implanted blastocysts [ ] . further evidence on these effects comes from a recent study in zebrafish. the exposure of zebrafish embryos and larvae to different concentrations of curcuma longa extract ( . , . , . , . , . , and . µg/ml) at different hours post fertilization (hpf: , , , , h) showed that a dosage above . µg/ml had toxic effects, and a dosage of . µg/ml increased embryo mortality and induced morphological deformities in larvae [ ] . despite the potential benefits of curcumin described in different pathological conditions, all these data indicate that dosage and time of exposure throughout pregnancy should be carefully evaluated to avoid serious damage to embryo development. the use of the natural product curcumin to treat medical conditions is spreading around the world. there is an increasing public interest in the potential health benefits of this compound, as evidenced by the large number of currently available curcumin formulations, aimed at increasing its bioavailability and efficacy, and by the considerable number of scientific papers published over the last years. this review has drawn attention towards the effects of curcumin on pregnancy and pregnancy complications, considering that during gestation, mother and fetus undergo significant (patho-) physiological changes. almost all data emphasizing the numerous biological activities of curcumin have been obtained from pregnant rodents and in vitro studies. curcumin appeared to ameliorate diabetes in a gdm mouse model, as well as pe in a pe rat model, and was found to be neuroprotective against environmental toxic agents. the antidepressant activity of curcumin has also been tested in humans. however, to date, studies on the possible beneficial effects of curcumin on ppd, a largely underestimated and understudied condition, are completely lacking. as regards fetal growth and development, curcumin counteracted the modifications associated with fgr and ptb in rodent models but negatively affected blastocyst stage, implantation and post-implantation embryo development in healthy animals. altogether, these results indicate that the use of curcumin in pregnancy must be carefully evaluated. the growing use of curcumin as self-medication along with the misleading perception that "natural" is the equivalent of "safe" are additional issues of concern. further studies are needed to clarify whether pregnancy might benefit from curcumin's properties; for this purpose, the collaboration between multidisciplinary scientific teams is essential to provide a holistic view of the complex networks between natural products and human physiology. systems biology and the recently developed network pharmacology represent new strategies to better comprehend the mechanisms underlying curcumin activities in the human body. maternal nutrition and birth outcomes dietary interventions for healthy pregnant women: a systematic review of tools to promote a 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products can play a significant role in mitigation of mercury toxicity mercury (hg) exposure and its effects on saudi breastfed infant's neurodevelopment comparison of pharmacological and genetic inhibition of cyclooxygenase- : effects on adult neurogenesis in the hippocampal dentate gyrus adverse effects of prenatal and early postnatal exposure to antiepileptic drugs: validation from clinical and basic researches fetal alcohol spectrum disorders: genetic and epigenetic mechanisms author contributions: conceptualization, c.s. and s.m.; pubmed search, t.f. and r.v.; writing-draft preparation, t.f. and c.s.; writing-review and editing, s.m., e.f. and a.z.; supervision and critical revision s.m., r.v. and c.s. all authors have read and agreed to the published version of the manuscript.funding: this review received no external funding. the authors declare no conflict of interest. key: cord- -cc j j authors: marcus, benjamin a.; achenbach, peter; ziegler, anette-gabriele title: typ- -diabetes: früherkennung und ansätze zur prävention: update date: - - journal: diabetologe doi: . /s - - -x sha: doc_id: cord_uid: cc j j the incidence of type diabetes is increasing, especially in young children. early diagnosis is possible in the asymptomatic stage of islet autoimmunity. screening is offered to high-risk families, but also feasible and useful in the general population, in studies such as fr da(plus) in bavaria (germany). complications at clinical manifestation can be prevented by early diagnosis. participation in experimental interventions to delay stage progression is possible. numerous approaches to secondary prevention are being pursued. treatment with the monoclonal antibody teplizumab successfully delayed progression to clinical diabetes in patients in stage . infants at high risk for developing type diabetes can be identified by genetic screening. primary prevention pursues, among others, the goal of preventing the onset of the autoimmune reaction. the point trial aims to improve immune tolerance to insulin by oral exposure in high-risk children and to delay or prevent the onset of autoimmunity. following up on the focus issue “early detection and preventive treatment of type diabetes” published in this journal in , this article gives an update on selected developments over the past years. große prospektive geburtskohorten haben unser verständnis für die entstehung des typ- -diabetes und den natürlichen verlauf dieser chronischen autoimmunerkrankung entscheidend vorangebracht, und tun dies ist auch weiterhin. wir kennen die genetischen faktoren, die das auftreten der erkrankung begünstigen. wir können einen typ- -diabetes heute durch den nachweis von inselantikörpern diagnostizieren, lange bevor es zu veränderungen des glukosestoffwechsels oder gar zu symptomen kommt. in einer bahnbrechenden präventionsstudie konnten die klinische manifestation bereits um mehrere jahre hinausgezögert und die betazellfunktion stabilisiert werden, was auch die suche nach ei-ner kausalen therapie befruchten könnte. das immer bessere verständnis der komplexen vorgänge, die zur fehlleitung des immunsystems und zur fortschreitenden zerstörung von betazellen führen, eröffnet darüber hinaus verschiedene ansatzpunkte, das entstehen von autoimmunität zu verhindern und den prozess aufzuhalten. im themenheft dieser zeitschrift früherkennung und präventive behandlung des typ- -diabetes -weichenstellungen für die zukunft [ ] vom juni wurden diese bereiche bereits ausführlich dargestellt. in diesem beitrag sollen als update ausgewählte neue ergebnisse und entwicklungen der letzten jahre vorgestellt werden. der nachweis von gegen unterschiedliche betazellantigene gerichteten autoantikörpern im blut ist der etablierte und derzeit wichtigste marker für den autoimmunprozess, der den typ- -diabetes charakterisiert. es kommt zu einem untergang der insulinproduzierenden zellen der bauchspeicheldrüse durch autoreaktive t-zellen mit zunächst langsam, dann kurz vor der manifestation rasch abnehmender insulinproduktion. eine gestörte glukosetoleranz lässt sich erst feststellen, wenn bereits ein großteil der betazellen ihrer funktion nicht mehr nachkommen kann. die wesentlichen autoantikörper sind insulinautoantikörper (iaa), glutamatdekarboxylaseautoantikörper (gada), antikörper ge-gen das insulinomassoziierte antigen (ia- a) und zinktransporter- -autoantikörper (znt a). autoantikörpern markiert das frühstadium des typ- -diabetes der nachweis von oder mehr dieser autoantikörper beim asymptomatischen kind ohne gestörten glukosestoffwechsel ist inzwischen als eines der frühstadien des typ- -diabetes (stadium ) anerkannt. beim stadium liegen zudem mäßig erhöhte nüchternglukosewerte und/oder eine gestörte glukosetoleranz vor. der (neu) manifestierte typ- -diabetes nach gültigen klinischen und laborchemischen kriterien ist das stadium (. tab. ). anhand in der covid- -pandemie leistet die fr da plus -studie einen über die typ- -diabetes-früherkennung hinausgehenden beitrag zur epidemiologischen forschung. mit einem von italienischen wissenschaftlern entwickelten, nichtkommerziellen verfahren werden die kapillarblutproben auch auf igg-antikörper (igg: immunglobulin g) gegen die rezeptorbindungsdomäne des s-proteins von sars-cov- ("severe acute respiratory syndrome coronavirus ") untersucht. der luciferaseimmunopräzipitationstest (lips) funktioniert nach einem ähnlichen prinzip wie der nachweis von iaa [ ] . dabei wird auch auf anonymisierte fr da-proben seit august zurückgegriffen. so kann die immunitätslage von kindern im stark betroffenen bayern vor und im gesamten verlauf der pandemie ermittelt werden [ ] . the incidence of type diabetes is increasing, especially in young children. early diagnosis is possible in the asymptomatic stage of islet autoimmunity. screening is offered to highrisk families, but also feasible and useful in the general population, in studies such as fr da plus in bavaria (germany). complications at clinical manifestation can be prevented by early diagnosis. participation in experimental interventions to delay stage progression is possible. numerous approaches to secondary prevention are being pursued. treatment with the monoclonal antibody teplizumab successfully delayed progression to clinical diabetes in patients in stage . infants at high risk for developing type diabetes can be identified by genetic screening. primary prevention pursues, among others, the goal of preventing the onset of the autoimmune reaction. the point trial aims to improve immune tolerance to insulin by oral exposure in high-risk children and to delay or prevent the onset of autoimmunity. following up on the focus issue "early detection and preventive treatment of type diabetes" published in this journal in , this article gives an update on selected developments over the past years. um zu prüfen, ob teplizumab die klinische manifestation verhindern kann, wurden in einer trialnet-studie angehörige von personen mit typ- -diabetes behandelt, die selbst bereits ein frühstadium mit multiplen inselautoantikörpern und eine dysglykämie oder gestörte glukosetoleranz (stadium ) entwickelt hatten. die ergebnisse dieser untersuchung, die für mehr als die hälfte der behandelten eine verdoppelung der zeit bis zur klinischen erkrankung auf jahre ergaben, wurden im new england journal of medicine (nejm) publiziert [ ] . somit konnte erstmals die manifestation der erkrankung wirksam hinausgezögert werden, was einen durchbruch für die präventive therapie des typ- -diabetes darstellt. in die doppelblinde, randomisierte und plazebokontrollierte phase- -studie wurden verwandte von patienten mit typ- -diabetes, oder mehr autoantikörpern und dysglykämie eingeschlossen, mehrheitlich kinder ab jahren und jugendliche. sie erhielten wochen lang -mal täglich infusionen mit teplizumab oder kochsalz. im followup erfolgten mindestens halbjährlich glukosetoleranztests, die nachbeobachtungszeit betrug im median etwas über jahre, % der probanden konnten über mehr als jahre nachverfolgt werden. bei ( %) der mit teplizumab behandelten teilnehmenden und ( %) von in der plazebogruppe wurde ein klinischer typ- -diabetes diagnostiziert. im ersten jahr nach der behandlung war der effekt besonders ausgeprägt: hier manifestierte sich die erkrankung nur bei ( %) teilneh-mern in der teplizumab-vs. ( %) in der plazebogruppe. jährlich erkrankten , % auf den diesjährigen "scientific sessions" der "american diabetes association" (ada) wurden daten aus dem erweiterten follow-up der studie vorgestellt -und bei der medianen hinauszögerung noch ein weiteres, ., jahr hinzugefügt. zudem war teplizumab in der lage, den c-peptid-abfall nach manifestation nicht nur zu bremsen, sondern signifikant umzukehren. dies könnte bedeuten, dass nicht nur die zerstörung der betazellen gestoppt, sondern auch die insulinproduktion in dysfunktionalen zellen teilweise wiederhergestellt wurde [ ] . auch wenn derzeit noch "nur" davon ausgegangen werden sollte, dass sich für die behandelten patienten der beginn der erkrankung weiter in die zukunft verschiebt und der effekt bei einer dauerhaft therapiebedürftigen erkrankung moderat erscheinen mag, wirkt sich gerade bei kindern jedes gewonnene klinisch gesunde jahr noch weit mehr aus als im erwachsenenalter. für eine individualisierte sekundärprävention interessant wird die tatsache, dass anhand von biomarkern -hla-merkmalen (hla: humanes leukozytenantigen) und dem fehlen von znt a -abgeschätzt werden kann, bei welchen patienten ein ansprechen auf die anti-cd -behandlung bessere erfolgschancen hat [ ] . inzwischen wurden mehr als genloci identifiziert, die in unterschiedlichem ausmaß für das entstehen eines typ- -diabetes prädisponieren. die meisten davon sind mit der immunantwort so-wie der entwicklung und dem erhalt von toleranz gegenüber antigenen assoziiert [ ] . die genetische empfänglichkeitalleinführtaberwahrscheinlichnicht zum entstehen der inselautoimmunität. es wird angenommen, dass umweltfaktoren, die auf eine genetische prädisposition treffen, entscheidend mit zur initiierung des autoimmunprozesses beitragen. dabei liegt es nahe, dass dem frühen säuglingsalter, in dem dieser prozess noch nicht in gang gekommen ist, eine besondere bedeutung zukommt [ ] . nichtpharmakologische interventionen zielen auf die zusammensetzung der ernährung und ggf. gezielte supplementationen ab, auch das darmmikrobiom rückt immer mehr in den fokus [ ] . in der interventionellen präventionsstudie babydiet wurde gezeigt , dass -obwohl die zu frühe einführung von gluten mit der beikost, vor dem . lebensmonat, mit einem höheren risiko einhergeht -eine darüber hinausgehende glutenfreie ernährung das entstehen der inselautoimmunität nicht verhindert. auch durch elimination anderer potenziell antigener proteine durch die verwendung stark hydrolysierter säuglingsmilch konnte in der prospektiven trigr-studie die diabetesinzidenz nicht gesenkt werden [ , ] . es lassen sich weiterhin keine über die allgemeingültigen empfehlungen zu einer gesunden säuglingsernährung hinausgehenden ernährungsmaßnahmen zur senkung des typ- -diabetes-risikos ableiten. die identifikation von neugeborenen und säuglingen mit einem hohen genetischen typ- -diabetes-risiko ist heute einfach und kostengünstig möglich, sodass sie auch in bevölkerungsweiten studien angeboten werden kann. die "global platform for the prevention of autoimmune diabetes" (gppad), ein netzwerk kooperierender wissenschaftler und institutionen [ ] , führt dies seit regional in europäischen ländern durch. in deutschland wird das virusinfekte werden mit dem typ- -diabetes in verbindung gebracht, insbesondere virale atemwegsinfekte in der frühen kindheit und infektionen mit enteroviren und durchfallerregern. hier könnten zukünftig entsprechende impfungen, z. b. gegen coxsackie-viren [ ] , oder antivirale therapien zur senkung des erkrankungsrisikos beitragen [ ] . dervorfast jahreneingeführten rotavirenimpfung wird ein kürzlich festgestellter geringer rückgang der diabetesinzidenz bei vollständig geimpften kindern zugeschrieben. hinweise hierzu lieferten retrospektive auswertungen aus australien und den usa [ , ] , wobei die ergebnisse einer weiteren amerikanischen analyse dies zuletzt wieder in frage stellten [ ] . zumindest lässt sich sicher sagen, dass auch die rotavirenimpfungso wie alle anderen empfohlenen schutzimpfungen -sich keinesfalls negativ auf das typ- -diabetes-risiko auswirkt. die erstmalige, wirksame verzögerung der manifestation mit teplizumab allein ist schon bemerkenswert [ ] , die mögliche reaktivierung zuvor nicht sezernierender betazellen könnte auch die entwicklung kausaler therapien mit vorantreiben. in größeren studien mit mehreren behandlungszyklen und in der weite-ren langfristigen nachbeobachtung der studienpatienten wird das potenzial der substanz weiter untersucht werden. die kombination mit anderen, schon im frühen stadium in klinischen studien eingesetzten, vielversprechenden und verträglichen immunmodulatoren wie z. b. abatacept oder niedrig dosiertem antithymozytenglobulin, die an anderen stellen der pathogenese des typ- -diabetes angreifen [ , ] , sowie mit weiteren aufkommenden betazellregenerativen therapien wird bereits geplant. studien zur früherkennung stoßen bei eltern auf zuspruch, und auch familien, die bisher nicht von typ- -diabetes betroffen waren, sind am angebot primärer und sekundärer präventionsstudien sehr interessiert. die möglichkeit, komplikationen bei der manifestation zu verhindern und erste erfolge in der medikamentösen sekundärprävention werden die schon länger geführte debatte um eine verstetigung und ausweitung von typ- -diabetes-früherkennungsuntersuchungen, z. b. als zusätzliches angebot bei den gesetzlichen vorsorgeuntersuchungen, sicher befruchten [ ] . früherkennung und präventive behandlung des typ- -diabetes typ- -diabetes im asymptomatischen frühstadium classification and diagnosis of diabetes: standards of medical care in diabetes- type diabetes the challenge of modulating β-cell autoimmunity in type diabetes type diabetes trialnet: a multifaceted approach to bringing disease-modifying therapy to clinical use in type diabetes predicting type diabetes using biomarkers birth and coming of age of islet autoantibodies a future for cd antibodies in immunotherapy of type diabetes rationale for enteroviral vaccination and antiviral therapies in human type diabetes association betweenrotavirusvaccinationandtype diabetes in children teplizumab preserves c-peptide in recent-onset type diabetes: two-year results from the randomized, placebo-controlled protégé trial etablierte früherkennungsstudie zu typ- -diabetes testet nun tausende kinder auch auf antikörper gegen sars-cov- an anti-cd antibody, teplizumab, in relatives at risk for type diabetes landmark models to define the age-adjusted risk of developing stage type diabetes across childhood and adolescence 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diabetes(t d)inpresymptomatic patients lower incidence rate of type diabetes after receipt of the rotavirus vaccine in the united states traveling down the long road to type diabetes mellitus prevention who is enrolling? the path to monitoring in type diabetestrialnet'spathwaytoprevention continuous glucose monitoring predicts progression to diabetes in autoantibody positive children a hexavalent coxsackievirus b vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates delaying diabetes onset the human gut microbiome in early-onset type diabetes from the teddy study früherkennung des typ- -diabetes in der fr da-studie identification of infants with increased type diabetes genetic risk for enrollment into primary prevention trials-gppad- study design and first results why is the presence of autoantibodies against gad associated with a relatively slow progression to clinical diabetes? oral insulin therapy for primary prevention of type diabetes in infants with high genetic risk: the gppad-point (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol yield of a public health screening of children for islet autoantibodies in bavaria key: cord- -wxfc aaz authors: kyle jacques, rose; renza, scibilia title: the covid pandemic – perspectives from people living with diabetes date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: wxfc aaz during the unprecedented times of the covid pandemic, the lives of people with diabetes have been severely impacted. this article discusses the extent of this impact presenting the obstacles and challenges from the perspective of the patient, including specifics of practical day-to-day diabetes self-management routines. since the covid outbreak, certain psychosocial factors have been amplified due to the manner in which mainstream media and policy makers have carelessly emphasized the vulnerability of people with diabetes. the authors discuss the increased importance of support networks due to people living in isolation and quarantine. a new layer of complexity has been added to the already difficult task of managing one's diabetes and it has increased anxiety and stress levels. guidelines and tips for people living with diabetes are discussed based on the authors' personal experiences as well as those of the diabetes associations they work with. living with diabetes is complex and can be overwhelming. add a global pandemic to the already monumental expectations placed on us to live healthily and maintain glucose levels in range, and it's not surprising that many people with diabetes are finding these trying times especially difficult. impact of the pandemic covid- has exacerbated many factors involved in diabetes care and increased stress. uncertainty around the new virus is frightening, and many people have the additional worry of loss of income . the pandemic has severely disrupted routine diabetes self-management, including: the covid pandemic -perspectives from people living with diabetes -food -scarcity of healthy foods, as well as having to change diets, makes consistent diabetes management challenging. certain products are not available. many restaurants and stores have closed or changed their hours. -medicine -going to the pharmacy or seeing your doctor has become more difficult, and some people have reported problems when trying to refill prescriptions. due to the risk of exposure to the virus, people are concerned about attending appointments, opting for telehealth/telemedicine when possible. -physical activity -there are obstacles to maintaining exercise, an essential element in diabetes therapy. space is limited in our homes, parks and gyms are closed and many people face restrictions to leaving the house. diabetes management is not only about glucose numbers. it is also about emotional well-being and mental health . during the pandemic, many people with diabetes have felt more anxious, even scared, about situations out of their control. while going into lockdown keeps us safe, it also has meant that our social circles, critical for support, have shrunk. not knowing how or when this will end can increase anxiety levels. as has been widely reported, the elderly and people with chronic health conditions, such as diabetes, are considered especially vulnerable to complications of covid- . the dismissive and insensitive manner in which this has been repeated by the media and policy makers has been upsetting for many of us. we feel 'disposable'. in addition to this constant reminder of our vulnerability are the often-unwelcome comments from the general community about how we should manage our diabetes. although frequently well-intentioned, this 'advice' creates enormous pressure, and adds to the already considerable social stigma we face . these comments rarely help and instead make us feel that we are being judged. support from our peers is particularly important during these unprecedented times. most often, it is those with first-hand diabetes experience who understand how difficult it is to achieve in-range glucose levels, and how covid- is impacting us. lifestyle changes, many rarely do two individuals react the exact same way to the exact same factor and there are many variables to consider . people with diabetes try to balance everything simultaneously while using glucose monitoring technology as a guide. often, it is a nonstop, all-consuming job which can be overwhelming enough without facing a pandemic. -keep in touch with your healthcare team, especially for urgent care. other medical problems don't stop during covid- , so it's important to seek help when you feel something is not right. an important example is keeping alert for signs of diabetic ketoacidosis. -do the best with the situation around you. in certain areas, particularly those with high population density, social distancing/ppe guidelines cannot be followed all the time. if proper infrastructure is not in place, for example, in factories, markets, schools, hospitals, or on public transport, families of people with diabetes should take as many precautions as possible. we understand that culture and society will not change overnight, but unfortunately covid- won't wait so it is important to address these risks as best as you can. -be safe. wash hands frequently, maintain physical distance, wear personal protective equipment such as masks, and avoid large gatherings. -whether you receive your news via television, radio, or internet/social media, if the constant stream is making you anxious, consider taking a break! it can be exhausting to hear about matters beyond our control day-after-day. rely on trusted sources of information, such as local diabetes organizations and the who. at a time when there is so much uncertainty, added stress in our daily lives is to be expected. since diabetes doesn't allow us to take a break, it's important to adopt a methodical approach to reducing risks where possible, keeping in mind that we all need support from time to time. together we are stronger, even with an extra few meters of space between us! conflict of interest: the authors declare no conflict of interest. funding: the authors received no funding from an external source. tracking the impact of covid- on the diabetes community in the united states psychosocial care for people with diabetes: a position statement of the ada. diabetes care covid- and diabetes: knowledge in progress i call it the blame and shame disease': a qualitative study about perceptions of social stigma surrounding type diabetes diabetes management in primary care key: cord- - h j wn authors: paolo fadini, gian; luca morieri, mario; boscari, federico; fioretto, paola; maran, alberto; busetto, luca; maria bonora, benedetta; selmin, elisa; arcidiacono, gaetano; pinelli, silvia; farnia, filippo; falaguasta, daniele; russo, lucia; voltan, giacomo; mazzocut, sara; costantini, giorgia; ghirardini, francesca; tresso, silvia; maria cattelan, anna; vianello, andrea; avogaro, angelo; vettor, roberto title: newly-diagnosed diabetes and admission hyperglycemia predict covid- severity by aggravating respiratory deterioration date: - - journal: diabetes research and clinical practice doi: . /j.diabres. . sha: doc_id: cord_uid: h j wn abstract aims we investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with covid- severity independently from confounders. methods we retrospectively analyzed data on patients with covid- hospitalized between february and april in an outbreak hospital in north-east italy. pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. newly-diagnosed diabetes was defined by hba c and fasting glucose. the primary outcome was a composite of icu admission or death. results subjects were included, of whom ( . %) had diabetes, including newly-diagnosed. patients with diabetes were older and had greater comorbidity burden. the primary outcome occurred in . % of patients with diabetes compared to . % in those without (rr . ; %c.i. . - . ; p< . ). the association was stronger for newly-diagnosed compared to pre-existing diabetes (rr . vs . ; p= . ). higher glucose level at admission was associated with covid- severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p< . ). admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. conclusion newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of covid- severity due to rapid respiratory deterioration. diabetes worsens the outcome of virtually any acute or chronic medical condition, resulting in a shortened life expectancy [ ] . mortality from infectious disease is also increased in patients with diabetes, especially for sepsis and pneumonia [ ] . since the very beginning of the sars-cov- pandemic, diabetes emerged as one of the most common comorbidities and a potential driver of poor outcomes [ ] . the prevalence of diabetes was higher among patients hospitalized for covid- who were admitted to the intensive care unit (icu) or died [ ] . meta-analyses of studies reporting the characteristics of patients according to covid- severity in china found that diabetes conferred a - fold increased rate of poor disease outcome [ , ] . these findings are in line with the available literature on the adverse prognostic impact of diabetes on other viral infections, including influenza [ , ] . it remains unclear whether diabetes drove such excess risk independently from confounders, including its complications and comorbidities. it is conceivable that patients with diabetes experienced a worse covid- outcome because of multiple organ damage due to micro-and macrovascular disease [ , ] . on the other side, whether the impact of diabetes on covid- outcome depends on glucose control is less appreciated. in a study conducted on chinese patients, diabetes was associated with higher mortality, but patients with good glycemic control had lower mortality compared to those with poorer control [ ] . optimal glycemic management can therefore be crucial to improve covid- outcome [ ] . finally, new-onset diabetes has been reported during covid- [ ] [ ] [ ] , but its impact on disease outcome has not been assessed. in patients with acute medical conditions, such as acute myocardial infarction, newly-detected diabetes has an adverse prognostic effect [ , ] . of note, newly-diagnosed diabetes is often linked with occult organ damage that shortens survival [ ] . in addition, stress hyperglycemia has been known for decades to drive an exaggerated inflammatory response in critically-ill individuals [ ] . in the present study, we investigated the role of pre-existing diabetes, newly-diagnosed diabetes, and admission glucose levels on the outcome of patients hospitalized for covid- . we eventually explored which were the mediators of a poor outcome associated with diabetes. this retrospective study was conducted by collecting anonymized patient's data from electronic medical records. the protocol conforms to the ethical guidelines of the declaration of helsinki. in agreement with national regulation on retrospective studies, the protocol was notified to the local ethical committee (no. ) and the need for patient's informed consent was waived. we retrieved data on all consecutive patients hospitalized for covid- between february st and april th at the university hospital of padova, which is located at the center of one of the first sars-cov- outbreaks in northern italy. we screened records of all patients admitted to the hospital with a positive pcr test for sars-cov- on upper or lower airway sample. pre-existing diabetes was defined based on self-reported history, prior electronic medical records reporting a diagnosis of diabetes, or ongoing therapy with glucose-lowering medications. newly-diagnosed diabetes was defined by a hba c value of mmol/mol ( . %) or higher; in the absence of an hba c determination, a random glucose level of . mmol/l ( mg/dl) or higher, accompanied by signs and symptoms of hyperglycemia was considered diagnostic. for all patients, we recorded the following information: demographics (age, sex), concomitant cardiovascular risk factors (smoke, hypertension, dyslipidemia), comorbidities (chronic obstructive pulmonary disease and history of cancer), complications (cardiovascular disease and microangiopathy), presence or absence of covid- related pneumonia or interstitial lung disease (ild), ongoing therapies before hospitalization. we collected information on symptoms of covid- upon admission (time from onset of symptoms to hospitalization; presence of fever, cough, dyspnea, and gastrointestinal symptoms). vital signs were recorded at admission and at their worst timepoint: systolic and diastolic blood pressure, heart and respiratory rate, oxygen saturation, pao / fio ratio. key laboratory exams included: fasting plasma glucose, hba c, lipid profile (total cholesterol, hdl cholesterol, triglycerides, and calculated ldl cholesterol), and serum creatinine for calculation of estimated glomerular filtration rate (egfr) using the ckd-epi equation. we also collected admission levels and worse levels of the following biomarkers related to inflammation (white blood cell count [wbc], c-reactive protein [crp], il- , pro-calcitonin), hematology and coagulation (hemoglobin, lymphocytes, platelets, d-dimer) and tissue injury (liver enzymes, troponin i, lactate). we reported the worst vital signs or biomarkers as the worst value measured during the entire hospital stay, regardless of whether it occurred at admission or during any other time of hospitalization. in some cases, worst values could coincide with admission values if admission values were the worst among all values recorded during the hospital stay. the following in-hospital treatments were recorded: low-flow and high-flow oxygen, non-invasive ventilation, intubation, use of specific drugs, such as lopinavir/ritonavir, azithromycin, other antibiotics, remdesivir, chloroquine / hydroxychloroquine, glucocorticoids, tocilizumab. the primary outcome was a composite of admission to the icu (including all subjects needing mechanical ventilation) or death. death from any cause, was considered as a separate outcome. among those who were discharged alive, time to discharge was considered as additional secondary outcomes. because duration of hospitalization was highly skewed and sometimes driven by non-clinical reasons (e.g. patients being unable to return to home because lacking social support), observation was censored at days. continuous variables are reported as mean ± standard deviation (sd) or as median (inter-quartile range), while categorical variables have been reported has percentages. between-group differences in clinical characteristics were evaluated with student t-test or chi-square for continuous and categorical variables, respectively. the association between diabetes, glucose levels and other variables of interest with categorical outcomes was evaluated with robust-error-variance poisson regression models [ ] . in order to identify possible confounding factors, these associations were tested in unadjusted models and in two different multivariable adjusted (mva) models with increasing complexity. model (mva ): adjusted for sex and age. model (mva ): adjusted for sex, age and pre-existing conditions or pre-hospital medications associated with covid- severity in mva . in order to test the mva, full dataset of variables were needed, thus missing data were handled by means of multiple imputation (mi). mi was performed with a fully conditional specification (fcs) algorithm [ ] obtaining imputed datasets including only covariates with less than % of missing values. outcome variables and main variables of interest (e.g. plasma glucose) were not imputed. outcome analyses were performed on each imputed dataset and the pooled estimated effects are presented [ ] . cox proportional hazard model was used to compare the patient's probability of being discharged alive. the differences between the association of pre-existing diabetes and newly-diagnosed diabetes with the primary and secondary outcomes were evaluated by means of z score (z score = (estimates -esitmates ) / √(se +se )). the differences in the association between glucose levels and primary outcome among subjects with or without diabetes was evaluated with the inclusion of an interaction term in the models. the association between fasting plasma glucose and the worst levels of clinical and laboratory parameters detected during hospital stay were represented graphically with scatter plots and described by pearson' r correlation coefficient. we evaluated which of these parameters explained the association between glucose levels and covid- severity outcome (i.e. being mediators). to be consider a candidate mediator, variables needed to be independently associated with both the primary outcome (tested using poisson regression with robust error variance) and with glucose levels (tested with linear regression). for those variables meeting these two conditions, we then quantified the possible mediation effect (in percentage) as the differences in the association between glucose and the primary outcome in the model adjusted by the candidate mediator (rr adjust ) as compared to the association in the model not adjusted by the candidate mediator (rr not-adjust ). therefore the mediation analyses was evaluated as: mediation = x [ln(rr not-adjust )-ln(rr adjust )]/ln(rr not-adjust ). statistical analyses were conducted with a significance threshold of p< . and were done in sas version . (ts m ), graphpad prism v . . . we included patients who tested positive for sars-cov- upon pcr analysis. of these, ( . %) had diabetes ( pre-existing and newly diagnosed). as compared to individuals without diabetes, those with diabetes were older, had a higher prevalence of hypertension, dyslipidemia, cardiovascular disease, and chronic kidney disease. in addition, preadmission use of statins, antiplatelet drugs and beta-blockers were more common among subjects with diabetes (table ). symptoms at admission were similar as were laboratory findings (except for fpg and hba c). participants with diabetes had more compromised respiratory function with lower pao /fio and higher respiratory rate (table ). in-hospital pharmacological treatments were similar in subjects with or without diabetes, except that diabetic patients more often received antibiotics other than macrolids (table ) . table s shows patients' clinical characteristics further stratified by pre-existing versus newly-diagnosed diabetes status. over a median observation time of days (iqr - ), patients ( . %) showed a severe course, defined as the primary outcome, of whom died ( . %). in unadjusted analysis, presence of diabetes (including pre-existing and newly-diagnosed) compared to its absence was associated with a higher incidence of the primary outcome ( . % vs . %; rr . ; % c.i. . - . ; p< . ; figure a ). several other pre-existing conditions were associated with covid- severity, including hypertension, cardiovascular disease, atrial fibrillation, ckd and copd (table s ). among prehospitalization treatments, use of arbs, novel oral anticoagulants, and systemic glucocorticoids was more frequent among patients with the primary severity outcome (table s ). compared to absence of diabetes, newly diagnosed diabetes (rr . ; % c.i. . - . ) showed a stronger association with the primary outcome than pre-existing diabetes (rr . , % c.i. . - . ). the difference in the rr for the primary outcome between pre-existing and newly-diagnosed diabetes was statistically significant (p= . ). in addition, higher fpg at admission was associated with covid- severity, with an increase in relative risk of % (rr . ; % c.i. . - . ; p< . ) for each mmol/l ( mg/dl) increase in fpg. this association was stronger among individuals without diabetes than in those with diabetes (p for interaction = . ; figure a) after adjusting for age and sex, the magnitude of the association between diabetes (pre-existing and newlydiagnosed altogether) and covid- severity remained significant (rr . ; % c.i. . - . ; p= . ; figure b ). other variables associated with severity in the age-and sex-adjusted analysis were chronic kidney disease and pre-hospitalization use of systemic glucocorticoids (table s ). the analysis was repeated splitting diabetes into pre-existing and newly-diagnosed. the association of preexisting diabetes was attenuated and no longer significant, whereas the association between newly-diagnosed diabetes with the primary outcome remained statistically significant. the association between fpg and the primary outcome remained significant after age-and sex-adjustment and yet with a larger effect on outcome among non-diabetic than diabetic subjects ( figure b ). we tested whether the associations of diabetes and fpg with covid- severity was independent from additional confounders. as shown in table s , the association between diabetes and the primary outcome was confirmed in all models, including those with preexisting comorbidities and medications used prior to hospitalization (rr . ; % c.i. . - . ; p= . ). similarly, the association between fpg and the primary outcome was confirmed in all models (table s ) , including those with pre-existing comorbidities and medications used prior to hospitalization (rr per each mmol/l = . ; % c.i. . - . ; p< . ). we found a similar mortality rate among those with or without diabetes ( . vs . %; unadjusted rr . ; % ci . - . ; p= . ). conversely, a significant association was detected between fpg and mortality (rr for each mmol/l increase . ; % ci . - . ; p= . ), but this association disappeared after adjustment for age and sex (rr . ; p= . ). we also found that a lower proportion of diabetic patients was discharged alive during the observation time ( . % vs . %; p< . ; table ) with a longer mean time to discharge (+ . days; p= . ; table ). in a time-to-event analysis, diabetes was associated with a % reduced probability of recovery after adjustment for age and sex (hr . ; % c.i. . - . ). among survivors, the duration of hospitalization was significantly longer for patients with as compared to those without diabetes in unadjusted (+ . days; % c.i. . - . , p< . ; table ) and age-and sex-adjusted models (+ . days; % c.i. . - . , p= . ). for each mmol/l higher fpg, there was a significant % lower probability of recovery (hr . % c.i. . - . ; p < . ) and longer duration of hospitalization (+ . days; % c.i. . - . ; p< . ). we found statistically significant correlations between admission glucose levels and most clinical-laboratory characteristics, recorded at their worst level, indicative of covid- severity or progression, including hemodynamic, respiratory, hematologic, inflammatory, and tissue damage biomarkers (figure ). we then evaluated whether these correlations could partially explain (i.e. mediate) the association between fpg and covid- severity outcome. we first identified clinical-laboratory characteristics (recorded at their worst level) significantly associated with covid- severity (independently from age and sex). then, we estimated what percentage of the effect of fpg on covid- severity was explained by the association between fpg and these variables. as described in table s and represented graphically in figure , we found that a decline in respiratory function variables was the major determinant of the detrimental effect of hyperglycemia on covid- severity. in this study, we found that newly-detected diabetes and admission hyperglycemia were more strongly associated with covid- severity outcome than pre-existing diabetes. a known diabetes status was more common among patients with severe covid- , defined by icu admittance or death. known diabetes remained associated with poor covid- outcome independently from age and sex, but not when adjusted for other baseline clinical variables, suggesting that such effect was mostly driven by concomitant factors and complications. on the other side, newly-detected diabetes remained associated with covid- severity in fully-adjusted analyses. upon a formal comparison, the association with the primary outcome was stronger for newly-diagnosed than for pre-existing diabetes. admission glucose levels were closely related to most clinical and biochemical parameters of covid- severity collected during hospitalization, including the pao /fio ratio. remarkably, for each mmol/l ( mg/dl) higher admission glucose, the probability of severe progression significantly increased by about % independently from any other clinical-biochemical variable. the association between hyperglycemia and covid- severity was significantly stronger for patients with newly-diagnosed diabetes than for those with pre-existing diabetes. our finding is consistent with prior literature indicating that, in patients with acute medical conditions, newlydetected diabetes is a powerful predictor of poor outcomes [ , ] . this may be at least in part driven by the fact that known diabetes is often associated with manifest organ damage that can be accounted for clinically and statistically [ ] . vice-versa, patients who are unaware of their diabetes status are most of the times unaware of ongoing organ damage too, as their treating physicians are. in addition, such occult organ damage cannot be accounted for in statistical adjustment. yet, our data argue that newly-diagnosed diabetes was predictive of covid- severity not only because of a possible masked multi-organ frailty, but also by the strong link between glucose levels and the outcome. we performed an analysis to evaluate which of the clinical-laboratory parameters of disease severity were mostly responsible for mediating the effect of hyperglycemia on the outcome. top results included respiratory parameters and white blood cell count, whereas other markers of inflammation and tissue damage were not among top mediators, suggesting that hyperglycemia drove a worse progression of respiratory failure. indeed, pao /fio directly reflects respiratory failure and drives icu admittance or mechanical ventilation [ ] . diabetes and hyperglycemia were previously found to cause a form of pulmonary disease known as "diabetic lung", featuring changes in lung volumes and diffusion capacity [ ] . speculatively, patients with admission hyperglycemia upon hospitalization for covid- might have a poorer outcome because of an underlying subclinical pulmonary remodeling [ ] . the diabetic lung is supposed to be driven at least in part by obesity and metabolic syndrome [ ] , but systemic inflammation and platelet dysfunction have been implicated in hyperglycemic pulmonary microangiopathy [ ] . since inflammatory overactivation and coagulopathy are major features of severe covid- [ ] , we speculate that hyperglycemia can directly accelerate disease course. the study has limitations that do not allow us to exclude alternative explanations. first, some clinical variables were not collected for all patients, due to the setting where covid- patients were followed, i.e. strictly isolated wards with limited contacts with health personnel. absence of data on body mass index (bmi) prevented us from adequately considering the confounding role of obesity [ , ] . in addition, hba c was not available for all patients, potentially biasing the detection of pre-existing hyperglycemia. although we were able to control for the use of pre-admission use of glucocorticoids, in most cases it was impossible to judge the duration of hyperglycemia prior to hospitalization for covid- in patients without known diabetes. therefore, whether these patients had undiagnosed diabetes or stress hyperglycemia due to the cytokine storm remains unclear. despite our attempts to control for major biases, we cannot rule out that residual confounding was driving a spurious non-causal association between hyperglycemia and severe covid- . for example, a more severe degree of inflammatory activation before hospitalization could drive both stress hyperglycemia and a subsequent severe disease course, even if hyperglycemia exerted no direct role on disease progression. in other terms, it is impossible to rule out that hyperglycemia is simply a biomarker of a more severe disease [ ] . nonetheless, our study has notable strengths, including the detailed clinical characterization of patients with inclusion of several biochemical inflammatory markers, and the rigorous statistical approach to bias. furthermore, the mediation analysis allows speculating on the processes that drove poor outcome of covid- patients presenting with admission hyperglycemia. finally, we wish to underline that, while this manuscript was under preparation, a study conducted on patients hospitalized for covid- at the union hospital in wuhan (china) found that newly diagnosed diabetes was associated with a higher risk of mortality than known diabetes [ ] . interestingly, patients without known diabetes but presenting with hyperglycemia had the worst outcome. the similarities with our study are striking, providing evidence that covid- presents with the same clinical features in distant countries and different healthcare models. this also markedly reinforces the clinical message that hyperglycemia is a strong prognostic factor for adverse outcomes during covid- . data availability. original data are available from the corresponding author at a reasonable request. when distribution of the dependent variable was highly skewed, the y scale was log transformed. table s . diabetes mellitus, fasting glucose, and risk of cause-specific death mortality from infectious diseases in diabetes. nutrition, metabolism, and cardiovascular diseases : nmcd practical recommendations for the management of diabetes in patients with covid- clinical characteristics of coronavirus disease in china. the new england journal of medicine diabetic patients with covid- infection are at higher risk of icu admission and poor short-term outcome prevalence and impact of diabetes among people infected with sars-cov- characteristics and outcome of viral pneumonia caused by influenza and middle east respiratory syndrome-coronavirus infections: a -year experience from a tertiary care center clinical courses and outcomes of hospitalized adult patients with seasonal influenza in korea the contribution of diabetic micro-angiopathy to adverse outcomes in covid- . diabetes research and clinical practice clinical characteristics and risk factors for mortality of covid- patients with diabetes in wuhan, china: a two-center association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes. cell metabolism outcomes in patients with hyperglycemia affected by covid- : can we do more on glycemic control? diabetes care covid- symptoms masking inaugural ketoacidosis of type diabetes diabetic ketoacidosis precipitated by covid- in a patient with newly diagnosed diabetes mellitus. diabetes research and clinical practice covid- infection may cause ketosis and ketoacidosis diabetes known or newly detected, but not impaired glucose regulation, has a negative influence on -year outcome in patients with coronary artery disease: a report from the euro heart survey on diabetes and the heart cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the allhat study prognostic significance of silent myocardial infarction in newly diagnosed type diabetes mellitus: united kingdom prospective diabetes study (ukpds) stress-hyperglycemia, insulin and immunomodulation in sepsis a modified poisson regression approach to prospective studies with binary data multiple imputation by fully conditional specification for dealing with missing data in a large epidemiologic study multiple imputation after + years hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region diabetic lung, an underrated complication from restrictive functional pattern to pulmonary hypertension the diabetic lung: an easy target for sars-cov- ? the metabolic syndrome, diabetes and lung dysfunction diabetic microvascular disease and pulmonary fibrosis: the contribution of platelets and systemic inflammation covid- cytokine storm: the interplay between inflammation and coagulation. the lancet respiratory medicine predicting mortality due to sars-cov- : a mechanistic score relating obesity and diabetes to covid- outcomes in mexico obesity is associated with worse outcomes in covid- : analysis of early data from newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with covid- key: cord- - ojvhwb authors: maddaloni, ernesto; d’onofrio, luca; alessandri, francesco; mignogna, carmen; leto, gaetano; pascarella, giuseppe; mezzaroma, ivano; lichtner, miriam; pozzilli, paolo; agrò, felice eugenio; rocco, monica; pugliese, francesco; lenzi, andrea; holman, rury r.; mastroianni, claudio maria; buzzetti, raffaella title: cardiometabolic multimorbidity is associated with a worse covid- prognosis than individual cardiometabolic risk factors: a multicentre retrospective study (covidiab ii) date: - - journal: cardiovasc diabetol doi: . /s - - - sha: doc_id: cord_uid: ojvhwb background: cardiometabolic disorders may worsen covid- outcomes. we investigated features and covid- outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. methods: we collected and compared data retrospectively from patients hospitalized for covid- with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [icu] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. results: of patients enrolled, those with diabetes (n = ), compared with those without diabetes (n = ), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (copd), higher levels of inflammatory markers and a lower pao /fio ratio. the risk of the primary composite outcome in the patients who completed the study as of may (th), , was higher in those with diabetes (adjusted odds ratio ((adj)or) . , %ci . – . , p = . ), hypertension ((adj)or . , %ci: . – . , p = . ) and copd ((adj)or . , %ci . – . , p = . ). patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions ((adj)or . %ci . – . , p = . ). the risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors ((adj)or . , . – . , (adj)p = . ). conclusions: patients with diabetes hospitalized for covid- present with high-risk features. they are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions. being frequent comorbidities in patients with covid- who require intensive care or die [ , ] . type diabetes, in particular, might hypothetically impact on all of the different aspects of sars-cov- infection, from the contagion to the clinical presentation and to disease severity [ ] . further, in-hospital hyperglycaemia has been associated with worse covid- outcomes [ ] , being a negative prognostic factor at hospital admission in both patients with and without diabetes [ ] . in addition, regardless of diabetes diagnosis, hyperglycaemia reduced the efficacy of treatment with tocilizumab in patients affected by covid- [ ] . on the other hand, a recent report from wuhan failed to show an independent association of type diabetes with covid- mortality after adjustment for other cardiovascular conditions [ ] . notably, most cardiometabolic disorders share a common pathogenic soil, often cluster together, and might reflect the same intermediate pathways that favour covid- progression [ ] [ ] [ ] . therefore, assessing the possible association of type diabetes with covid- outcomes based on individual cardiometabolic disorders may be subject to a collider bias, leading to distorted results [ , ] . this makes it difficult to disentangle independent associations covid- may have with single components of cardiometabolic multimorbidity, defined here as a group of main metabolic disorders that increase the risk of cardiovascular events, such as diabetes, hypertension and dyslipidaemia. nevertheless, most studies investigating diabetes as a risk factor for covid- progression searched for independent associations, leading to conflicting conclusions [ , [ ] [ ] [ ] . we, instead, hypothesized that people with diabetes may differ from those without diabetes in their clinical presentation, course and prognosis of covid- due to the propensity of diabetes to cluster with other cardiometabolic risk factors, such as hypertension and/or dyslipidaemia, which contribute to the increased pro-inflammatory and hypercoagulable states of people with diabetes. furthermore, most studies published to date on this topic come from asian countries, with few data available from western countries where differences in ethnic groups and healthcare systems may lead to different associations [ , ] . overall, there is an urgent need for additional data to clarify the relationships between diabetes, cardiometabolic multimorbidity and covid- [ ] which could provide significant insights of global health interest to help tackle this deadly pandemic in a large group of atrisk individuals. we aimed to describe in detail, using opportunistic data collected retrospectively, the clinical and biochemical features of patients with and without diabetes hospitalized for covid- in four academic hospitals in the lazio region, italy, to evaluate their outcomes, and to evaluate the impact of cardiometabolic multimorbidity. the covid- & diabetes (covidiab) study is a multicenter observational study which collected data retrospectively from medical charts of patients hospitalized for covid- from march st to may th , in four academic hospitals located in the lazio region of italy: umberto i "policlinico" general hospital and sant' andrea hospital, sapienza university of rome; santa maria goretti hospital, polo pontino of sapienza university in latina; campus bio-medico university hospital in rome [ ] . patients eligible for inclusion were aged ≥ years old with a diagnosis of covid- confirmed by at least one real-time polymerase chain reaction assay, in accordance with the protocol established by the world health organisation [ ] . after exclusion of patients with unknown diabetes status, baseline data for patients and clinical outcomes for patients up to may th , were available for inclusion in this analysis. the covidiab primary aim was to evaluate whether patients with diabetes, compared with those without diabetes, were at increased risk of adverse covid- outcomes, independent of age and sex. the composite primary outcome was defined as any of mechanical ventilation, admission to an intensive care unit (icu), or death. pre-specified secondary endpoints included a composite outcome of icu admission or death and allcause mortality (acm). in this study, we did not seek to test whether diabetes as a risk factor for covid- progression is independent of hypertension and dyslipidaemia, which may be considered as coexisting components of a single cardiometabolic disorder (or syndrome). instead, our secondary aim (if diabetes was confirmed to be associated with an increased risk of the primary composite outcome) was to evaluate whether cardiometabolic multimorbidity (defined as ≥ of three risk factors of diabetes, hypertension and dyslipidaemia) may be considered as a risk factor that differs from a single cardiometabolic condition. accordingly, patients were stratified into three mutually exclusive cardiometabolic groups: no conditions, one condition and two or three conditions. data collected included: demographic information (age and sex); presence of diabetes (defined as at least one random blood glucose value > mg/dl, or fasting blood glucose > mg/dl, or hba c > . %, or self-reported history of diabetes with ongoing anti-diabetes therapy), type of diabetes (type , type , other); smoking habits (never, ex, current); prior history of hypertension, dyslipidemia, chronic obstructive pulmonary disease (copd), heart failure, cardiovascular events (myocardial infarction, percutaneous coronary intervention, coronary artery-bass graft or stroke), malignancy (any neoplasia diagnosed within the last five years or active neoplasia); presenting symptoms of sars-cov- infection (fever, cough, cold, conjunctivitis, chest pain, dyspnea, nausea, vomiting, diarrhea). biochemical data measured at admission, where available, were: plasma glucose, serum creatinine, erythrocyte sedimentation rate (esr), c-reactive protein (crp), full blood count, lactate dehydrogenase, fibrinogen, d-dimer and blood gas analysis. body mass index (bmi) was calculated for the patients with height and weight data available. usual care medications at admission were ascertained from those reported by the inpatient-accepting physician. diabetes usual care medications were also retrieved from the web-based reimbursement system of lazio region (web-care lazio), as categorized by this system: euglycaemic agents (eugla: metformin, dipeptidyl peptidase inhibitors [dpp i], glucagon-like peptide receptor agonists [glp- ra], sodium-glucose co-transporter inhibitors [sglt i] and/or pioglitazone); oral hypoglycaemic agents (oha: sulfonylureas or glinides); basal insulin (alone or in combination with eugla or oha); multiple daily insulin injections (mdi: ≥ insulin injections per day). the webcare lazio system was also used to confirm a self-reported history of diabetes. continuous variables are presented as medians [ th- th percentile]. categorical variables are presented as number and percentages, calculated on the data available. we made no assumptions regarding missing data. kruskal-wallis, chi-squared and fisher exact tests were used for comparisons between groups, as appropriate. we estimated that at least patients completing the study would be required to provide % power to detect a . -fold higher incidence of the primary composite outcome in patients with diabetes hospitalized for covid- , compared with those without diabetes, using a one-sided alpha-level of . and allowing for adjustment of sex and age. logistic regression models adjusted for age and sex were used to investigate associations of the primary and secondary outcomes with diabetes, and with other risk factors explored in the study, namely hypertension, dyslipidemia, copd, heart failure, previous cardiovascular events, malignancy and smoking status (never vs. ever). the secondary aim of the study (association of cardiometabolic multimorbidity with the primary composite outcome) was also explored using a logistic regression model adjusted for age, sex and risk factors (other than hypertension, diabetes and dyslipidemia) that were univariately associated (p < . ) with the outcome after correction for age and sex. the wald test was used to test equality of the regression coefficients between cardiometabolic groups. stata/ic . software was used for data analysis and prism . software for graphical presentations. covidiab complies with the principle of the helsinki declaration and was approved by the ethical committee of umberto i "policlinico" general hospital. because of the study's retrospective design, informed consent was waived for patients who had been discharged, could not be contacted, or died. the privacy and anonymity of the data collected was guaranteed in accordance with current regulations. presenting characteristics for all patients are listed in table . patients with diabetes, compared with those without diabetes, were older (age ≥ years: . % vs. . %, p < . ) but with a similar sex distribution. they also presented with higher rates of hypertension ( . % vs. . %, p = . ), dyslipidemia ( . % vs. . %, p < . ), prior cardiovascular events ( . % vs. . %, p = . ), heart failure ( . % vs. . %, p = . ) and copd ( . % vs. . %, p = . ). no differences in smoking habits or malignancy rate were found. bmi did not differ between patients with and without diabetes. at no differences were observed in the frequencies of sars-cov- infection presenting symptoms between patients with and without diabetes (additional file : table s ). continuous variables are presented as median [ th, th percentile]; categorical variables are presented as number (percentage) # p-value for difference in never, ex and current mokers eugla, euglycemic agents (metformin, dipeptidyl peptidase inhibitors, glucagon-like peptide receptor agonists, sodium-glucose co-transporter inhibitors and/ or pioglitazone); oha, oral hypoglycaemic agents (sulfonylureas or glinides); mdi, multiple daily insulin injections; raas, renin-angiotensin-aldosterone system; acei, angiotensin converting enzyme inhibitors; arb, angiotensin receptor blocker; cv, cardiovascular; copd, chronic obstructive pulmonary disease; esr, erythrocytes the primary composite outcome occurred in ( . %) of the patients who completed the study (discharged alive or experiencing at least one component of the primary composite outcome). differences in clinical features between those experiencing the primary composite outcome and those discharged alive (n = ), mostly mirrored the differences seen between patients with and without diabetes ( table ) . those with, compared with those without the primary composite outcome, were more often > years old (p < . ) and more likely to have hypertension (p < . ), dyslipidemia (p = . ), heart failure ( . ) or copd (p = . ). there was no difference in prior history of cv events between groups but those with the primary composite outcome were less often current smokers than never smokers ( . % vs. . %, p = . ). bmi in the patients with bmi data and complete follow-up, was higher in those with the primary composite outcome compared with those discharged alive not requiring neither icu admission or mechanical ventilation ( differences in biochemical features between patients with, compared with those without the primary composite outcome, also paralleled the differences seen between patients with and without diabetes (table ) . those experiencing the primary composite outcome had higher plasma glucose (p < . ), serum creatinine (p = . ), crp (p < . ), white blood cell count (p < . ), neutrophil count (p < . ) and venous lactate (p = . ), and a lower pao /fio ratio (p < . ). they also had higher lactate dehydrogenase (p < . ) and d-dimer (p = . ) concentrations, but had a lower lymphocyte count (p = . ). frequencies of sars-cov- infection presenting symptoms were similar among patients with, compared with those without the primary composite outcome, apart from dyspnea which was more frequent among those experiencing the primary composite outcome ( . % vs. . %, p < . ) (additional file : table s ). age and sex adjusted regression models confirmed that covid- patients with the primary composite outcome were more likely to have diabetes (adjusted odds ratio [ adj or] . , % confidence interval [ci] . - . , p = . ), hypertension ( adj or . , %ci . - . , p = . ) or copd ( adj or . , %ci . - . , p = . ), while the associations with dyslipidemia and heart failure were lost (fig. a) . therapies for diabetes at admission did not differ between patients with diabetes in whom the primary composite outcome did or did not occur (table ) . similarly, there was no difference in the use of angiotensinconverting enzyme (ace) inhibitors or angiotensin receptor blockers (arb) between patients who did or did not experience the primary outcome ( . % vs . %, p = . and . % vs . %, p = . , respectively). of the patients completing the study, ( . %) did not have diabetes, hypertension or dyslipidaemia, ( . %) had just one of these risk factors ( with diabetes, with hypertension, with dyslipidaemia), and ( . %) had ≥ two of these risk factors meeting our study definition of cardiometabolic multimorbidity. the proportion of patients > years old (p < . ), with a prior cardiovascular event (p < . ), heart failure (p = . ) or copd (p = . ), and higher concentrations of plasma glucose (p < . ), creatinine (p = . ), crp (p = . ) and venous lactate (p < . ) increased with increasing numbers of cardiometabolic conditions, and with a decreasing pao /fio ratio (p = . ) ( table ) . the proportion of patients experiencing the composite primary outcome increased with increasing numbers of cardiometabolic risk factors (fig. ) , independently of age, sex and copd ( adj p = . ). the risk of the primary composite outcome in patients with cardiometabolic multimorbidity, compared with those with no cardiometabolic risk factors, was higher ( adj or [ % ci] . [ . - . ], adj p = . ). they also were at higher risk when compared with patients with a single cardiometabolic risk factor ( adj or . , . - . , adj p = . ). the risk for patients with a single cardiometabolic risk factor, however, did not differ with that for those with no cardiometabolic risk factors ( adj or . , . - . , adj p = . ). analyses examining the secondary outcomes of icu admission or death, and acm alone, were performed for patients who were admitted to icu, died or were discharged alive without icu admission (n = ), and for the those who died or were discharged alive at study end (n = ). icu admission or death occurred in ( . %) sedimentation rate; crp, c-reactive protein; pao , arterial po ; fio , fraction of inspired oxygen body mass index data were available for * , ** , *** and **** patients smoking data were available for ^ , ^^ , ^^^ and ^^^^ patients anti-diabetes therapy data were available for of the patients with diabetes who completed the study fig. proportion of patients experiencing the primary composite outcome (a), and the secondary outcomes of icu admission or death (b), or death (c) among patients with or without different comorbidities. age and sex adjusted odds ratios (or) with % confidence intervals (ci) for those with, compared with those without, each comorbidity are reported. error bars represent % confidence intervals in the former, and ( . %) of the latter died. after adjustment for age and sex, diabetes was not associated with either of these secondary outcomes, whereas a prior history of copd or heart failure was (fig. b, c and additional file : table s ). our study shows that the characteristics associated with worse covid- outcomes are found more frequently in patients with diabetes than in those without diabetes. these include older age, higher prevalence of chronic comorbidities such as hypertension or copd, higher levels of inflammatory markers, and a lower pao /fio ratio. accordingly, the risk of progression towards mechanical ventilation, icu admission or death was significantly higher among patients with diabetes than in those without, independent of age and sex. as we expected, only a minority of patients with diabetes ( . %) had neither hypertension nor dyslipidemia, supporting our choice not to consider these risk factors as independent variables. this observation suggests that findings from studies reporting diabetes is not associated with covid- severity after adjustment for other cardiovascular conditions should be interpreted with caution [ ] . in line with our hypothesis, patients with cardiometabolic multimorbidity had a higher risk of the primary outcome compared with patients with no or a single cardiometabolic risk factor (diabetes, hypertension or dyslipidaemia). compared with patients with no cardiometabolic risk factors, the primary composite outcome was also higher among patients with a single risk factor, but was not significant after adjustment for age, sex and presence of copd. of note, while drugs targeting the incretin system or the renin-angiotensin-aldosterone system have been hypothesized to be associated with covid- outcomes [ , ] , their use did not differ between patients with or without the primary outcome. overall our results confirm previous findings from other countries that covid- patients with diabetes are more likely to require intensive care or to die, compared with covid- patients without diabetes [ , , , ] , and in addition suggest this association is driven by the presence of cardiometabolic multimorbidity rather than by diabetes alone. in this regard, categorizing patients as having cardiometabolic multimorbidity, rather than a simply summing risk factors [ ] , seems to almost completely explain the interaction between cardiometabolic disorders and covid- . coexisting cardiometabolic risk factors may indeed either be the expression of a common pathogenic soil or cooperate with each other to predispose covid- patients to progress towards more severe clinical scenarios. in patients presenting with diabetes but not hypertension or dyslipidemia, pathogenic pathways involved may not be sufficiently affected to impact on the clinical course of covid- . the observation that cardiometabolic multimorbidity worsens covid- is of clinical relevance, highlighting the importance of tackling cardiovascular risk as a whole to improve covid- outcomes. of note, an estimation of the overall effects of the covid- outbreak according to underlying conditions has also suggested that cardiovascular comorbidities, together with copd, may be responsible for the majority of excess deaths associated with covid- pandemic from both direct and indirect effects [ ] . different mechanisms may be hypothesized to explain the association of cardiometabolic health with covid- outcomes. it has been suggested that covid- not only affects the respiratory system but also the vasculature [ ] [ ] [ ] [ ] . direct sars-cov- infection of endothelial cells causing endothelitis in several organs has been demonstrated in patients dying from covid- [ ] , suggesting covid- is an infectious disease affecting endothelial function. it is worth hypothesizing therefore, that cardiometabolic multimorbidity may predispose to worse covid- outcomes by weakening endothelial cells [ ] , which then become more susceptible to viral infection. additionally, the hypercoagulable and pro-inflammatory states often observed in cardiometabolic patients [ ] may also contribute towards the formation of the multiple blood clots and the cytokine storm that can occur in the most severe covid- cases [ , ] . this endothelial hypothesis accords with recent data suggesting that a high amount of visceral adiposity, a common feature of cardiometabolic patients associated with chronic lowgrade inflammation, associates with worse covid- outcomes [ ] . while measures of visceral adiposity were not available in our study, bmi was found to be higher in patients with the primary outcome, consistent with previous reports in other populations [ , ] . the trend we noted towards higher bmi with increasing number of cardiometabolic risk factor in the relatively low number of patients with bmi data available our population was not statistically significant. limitations to our study include retrospective collection of data from electronic and paper records, relatively few patients with bmi data available, and incomplete followup of some patients without an endpoint who were still hospitalized at the time of this analysis. also, we were not able to retrieve glycemic control data during hospitalization, which has been associated with worse covid- outcomes [ , ] . the small number of deaths does not allow us to make any conclusions about the non-significant association of diabetes with acm, which was however associated with prior history of hypertension, copd or heart failure. finally, we were not able to estimate insulin resistance, or surrogates such as triglyceride-glucose index [ ] , in our population, which is often considered the common soil for cardiometabolic conditions. similarly, the absence of waist circumference data not allow us to identify patients with the metabolic syndrome to assess its possible impact, although the utility of this categorisation in type diabetes has been increasingly questioned [ ] . unfortunately, due to the observational study design and the demanding work condition determined by the pandemic, we were unable to collect additional blood samples or to perform additional radiological investigations to test bio-markers not routinely measured in all patients, such as cardiac troponin, interleukins, or to assess visceral adiposity, all of which may be involved in the relationship between cardiometabolic multimorbidity and covid- progression [ , , ] . novel studies should be performed to evaluate whether the increased risk conferred by cardiovascular multimorbidity is associated to augmented cytokine storm and to central obesity. strengths of our study include a detailed characterization of the clinical and biochemical features of patients hospitalized for covid- , with and without diabetes, with good generalizability of the results thanks to the multicentre study design. furthermore, to the best of our knowledge, this is the first study assessing covid- outcomes in the context of cardiometabolic multimorbidity. our study shows that patients with diabetes hospitalized for covid- present with high-risk clinical and biochemical features and are at increased risk of mechanical ventilation, icu admission or death, likely because diabetes frequently clusters with cardiometabolic multimorbidity. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : table s . sars-cov- infection symptoms at hospitalization in patients with, compared with those without, diabetes and in patients experiencing the primary composite compared with those without. table s . odds ratio (or) with [ % confidence intervals, ci] for secondary outcomes, unadjusted and adjusted for age and sex. abbreviations: cv, cardiovascular; copd, chronic obstructive pulmonary disease. characteristics of hospitalized adults with covid- in an integrated health care system in california clinical characteristics of covid- in new york city clinical characteristics of coronavirus disease in china presenting characteristics, comorbidities, and outcomes among patients hospitalized with covid- in the baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region italy impact of diabetes mellitus on clinical outcomes in patients affected by covid- are patients with hypertension and diabetes mellitus at increased risk for covid- infection? covid- and diabetes mellitus: unveiling the interaction of two pandemics outcomes in patients with hyperglycemia affected by covid- : can we do more on glycemic control? diabetes care hyperglycaemia on admission to hospital and covid- negative impact of hyperglycaemia on tocilizumab therapy in covid- patients clinical characteristics and risk factors for mortality of covid- patients with diabetes in wuhan high-risk multimorbidity patterns on the road to cardiovascular mortality multimorbidity of cardiometabolic diseases: prevalence and risk for mortality from one million chinese adults in a longitudinal cohort study multimorbidity: another key issue for cardiovascular medicine educational note: paradoxical collider effect in the analysis of non-communicable disease epidemiological data: a reproducible illustration and web application collider bias undermines our understanding of covid- disease risk and severity. medrxiv covid- in people with diabetes: urgently needed lessons from early reports diabetes is a risk factor for the progression and prognosis of covid- association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes frailty and geography: should these two factors be added to the abcde contemporary guide to diabetes therapy? cardiovascular multimorbidity: the effect of ethnicity on prevalence and risk factor management clinical features of patients with type diabetes with and without covid- : a case control study (covidiab i) world health organization. laboratory testing for coronavirus disease (covid- ) in suspected human cases could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with covid- infection? data from centers of southern italy dpp inhibition: preventing sars-cov- infection and/ or progression of covid- ? diabetes comorbidity and its impact on patients with covid- in china: a nationwide analysis estimating excess -year mortality associated with the covid- pandemic according to underlying conditions and age: a population-based cohort study covid- diagnosis and management: a comprehensive review pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid- potential effects of coronaviruses on the cardiovascular system hypertension, thrombosis, kidney failure, and diabetes: is covid- an endothelial disease? a comprehensive evaluation of clinical and basic evidence endothelial cell infection and endotheliitis in covid- vascular complications of diabetes: mechanisms of injury and protective factors prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs hypercoagulability of covid- patients in intensive care unit. a report of thromboelastography findings and other parameters of hemostasis facing covid- in the icu: vascular dysfunction, thrombosis, and dysregulated inflammation the role of visceral adiposity in the severity of covid- : highlights from a unicenter cross-sectional pilot study in germany letter to the editor: obesity as a risk factor for greater severity of covid- in patients with metabolic associated fatty liver disease triglyceride-glucose index is associated with symptomatic coronary artery disease in patients in secondary care impact of the metabolic syndrome on macrovascular and microvascular outcomes in type diabetes mellitus cardiac troponin for the diagnosis and risk-stratification of myocardial injury in covid- : jacc review topic of the week em designed the study, analysed and interpreted data and wrote the first draft of the manuscript. ldo contributed to the design of the study, data acquisition, interpretation and manuscript writing. cm acquired data and helped in data interpretation; fa, gl, im, ml, fea, fp, and gp acquired data. pp, mc, al revised the manuscript for important intellectual content. rrh contributed to data interpretation and revised the manuscript for important intellectual content. cmm contributed to the design of the study and acquisition of the data. rb was responsible for the conception of the study, contributed to study design and data interpretation and revised the manuscript critically for important intellectual content. all authors read and approved the final manuscript. the study was in part supported through the efsd mentorship programme supported by astrazeneca. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. covidiab complies with the principle of the helsinki declaration and was approved by the ethical committee of umberto i "policlinico" general hospital. because of the study's retrospective design, informed consent was waived in cases of discharge, of impossibility of contact with patients and in case of death. the privacy and anonymity of the data collected was guaranteed in accordance with current regulations. not applicable. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - w bqrox authors: aghdam, atae rezaei; watson, jason; miah, shah j; cliff, cynthia title: towards empowering diabetic patients: a perspective on self-management in the context of a group-based education program date: - - journal: nan doi: nan sha: doc_id: cord_uid: w bqrox this paper provides a novel framework for maximizing the effectiveness of the diabetes group education program, which could be generalized in any similar problem context. diabetes is recognised as the world's fastest-growing chronic disease (australia ; lovic et al. ) . according to the international diabetes federation (idf), by one adult in ten will have diabetes ( million) (australia ). diabetes is a chronic and progressive disease, which needs continuing self-management and self-awareness for a lifestyle change (kjellsdotter et al. ) . selfmanagement is one of the most key success factors impacting the progression of type- diabetes for patients, as the decisions that they make daily considerably impact their health outcomes (funnell and anderson ) . patients play a pivotal role in their self-care as they are doing more than % of their diabetes care outside of medical centres or at home (su et al. ) . ohcs as affordable and easily accessible / services, can facilitate self-management of diabetics by offering health-related advice and stories, social and emotional support (aghdam et al. ). an ohc refers to a group of people who interact with each other in an online platform about similar health issues (wang et al. ) . due to the fact that people tend to trust others who are in a similar situation rather than organisations, businesses, or government figures and media, it stands to reason that the content shared by peers in ohcs has potential to encourage community members to engage in health-related online activities (irshad et al. ; litchman and edelman ) . participating in ohcs progressively transforms patients from passive recipients of healthcare services to active agents (bragazzi ) . as active agents, patients can access, share and integrate their resources, sharing their experiences and stories, and emotionally supporting peers to achieve their health-related goals (forouzandeh and aghdam ) (aghdam et al. ) . the empowerment of patients improves the patients' role in co-creation, co-designing, and co-delivering health services (ciasullo et al. ) . this is essentially a reality for people with chronic disease such as diabetes patients who need informational and emotional supports that allow them to be successful in their disease self-management (litchman and edelman ) . in this regard, the diabetes education program has been a focus of prior research as a specific intervention that supports diabetes self-management (findlay-white et al. ) . ohcs provide opportunities for members to exchange new ideas, knowledge and information about diabetes selfmanagement, functioning as a bridge among people with type- diabetes and healthcare professionals and providing online discussion platforms to brainstorm potential solutions (sim et al. ) . as such, this study aims to investigate the potential practices of online diabetes communities to address the following question; how can an online diabetes community empower patients in context of a diabetes group education program (dgep)? the remainder of this paper is organised as follows; the next section describes the background of the literature. the following section explains the research methodology followed by the trustworthiness process. the discussion section provides a comprehensive overview of the contributions of the study from both theoretical and practical perspectives and the final section synthesises the findings and provides avenues for future research. chronic disease is generally of long duration, slow progression, and impacts the quality of life (martz et al. ). the care for people with chronic diseases such as type- diabetes is often complex and requires self-management as an essential element of the chronic care model (wagner et al. ). self-management includes actions and behaviours to manage the psychical, emotional, and social effects of the chronic disease (adams et al. ). one of the key methods for self-management of chronic disease and improved health outcomes is patient education (ellis et al. ; mensing and norris ) . patient education is the keystone of chronic disease self-management and is significant in achieving positive health outcomes for chronic disease patients (ellis et al. ; mensing and norris ) . patients need support, education, guidance and empowerment from their healthcare providers to tackle barriers to effective self-management (diabetes ). studies contended that participation in self-management courses also improves patient confidence, self-management skills and ability to self-manage their chronic disease, and improves the quality of life (turner et al. ) . diabetes group education programs typically assist patients to achieve knowledge and skills and confidence to manage their diabetes as well as opportunities to interact with peers and healthcare providers (jonkman et al. ) . group interactions facilitate further learning and raise motivation by interacting and learning from the experience of others (odgers-jewell et al. ) . research shows that diabetes group-based education programs benefit patients who derive social and emotional support from discussion with others (steinsbekk et al. ). this type of active participation by australasian conference on information systems aghdam & watson , wellington towards empowering diabetic patients patients in their health journey leads to value co-creation (osei-frimpong et al. ) . in the healthcare context value co-creation refers to "activities centered around the individual patients or in collaboration with numbers of the service delivery network including the patient, family, friends, other patients, health professionals and the outside community" (mccoll-kennedy et al. , p. ) . value is co-created synergistically and digital health platforms such as ohcs act as a coordinating device between community members (smedlund ) . thus, digital health platforms such as ohcs are ideal places for value co-creation (aghdam et al. ; kamalpour et al. ) . because of the nature of the dgep, patients face three different stages during their health journey; ( ) prior to joining, ( ) during the program, and ( ) after the program. we adapted customer-dominant logic (cdl) to divide the customer journey into these three phases. in fact, cdl argues that customers control the service situation and control is a relevant issue in many domains, and due to progressively empowered customers (seybold ) , this direction will most likely continue in the future (heinonen and strandvik ) . accordingly, in the healthcare domain, empowering patients in ohcs can activate value co-creation behaviour among stakeholders (litchman et al. ). as diabetes self-management requires a patient-centred approach (funnell et al. ) , in particular for a demand-driven decision making (e.g. in clinical settings -miah, ) and to date, the most successful diabetes self-management group activities and classes have been evaluated based on empowerment theory (heisler ) , our study applied empowerment theory in the context of ohcs and a diabetes group education program. empowerment theory contends that actions, activities or structures might be empowering and the outcome of such process leads to being empowered (zimmerman ) . according to empowerment theory, people need opportunities to become active in community decision-making to improve their quality of life. as such, we leverage an affordable and easily accessible / digital health platform such as ohcs to facilitate the process of selfmanagement through informational, social, and emotional support. the proposed framework goes beyond the existing system-centric approaches to a new mode of conceptualisation and practice, which focuses on interactions among all stakeholders in ohcs. the proposed framework addresses diabetesrelated needs and challenges including; informational, social, and psychological needs. in this study, we selected online reddit diabetes communities as our data source. the interactions between users are mostly focused on the posts themselves and members will give the post all their attentions. there are numerous diabetes-related topics in this forum, which make it a promising source of users' interactions for this research study. reddit is a social aggregation and public discussion website. in reddit, three popular diabetes communities comprise of more than , members. in this study, we selected r/diabetes, r/type diabetes, and r/diabetes_t communities. within each community, there are a variety of threads and topics discussed by users. the total number of users in all of these communities was , in april . from each topic, the tile and the content (e.g., textual information) were extracted without the additional information of the authors. a total of topics were collected from reddit from october to april . in total threads were collected for analysis. research argued that participation in diabetes group education program has multiple benefits for patients such as social and emotional support, and sharing experiences (odgers-jewell et al. ) . the queensland university of technology (qut) offers a partnership face-to-face dgep to patients who are newly diagnosed or living with the type- diabetes long term. over the course of program, the qut dgep aims to provide a quality lifestyle intervention empowering type- diabetic patients to better manage their symptoms. the dgep runs for weeks and includes various types of activities such as; initial assessment, weekly one-hour personalized exercise session, one-hour interactive group education regarding diabetes-related topics (e.g., diet, mindfulness, foot care, living with a chronic condition, etc.), and a final assessment at the end of the program. the outcomes of this award-winning program are promising and all patients involved no longer needing to stay on the long waiting list of the hospitals. one of the most important objectives of the dgep is to keep patients connected whilst outside the program. we, therefore, aim to extend the value of the face-to-face dgep by identifying the potential practices on the online diabetes communities, proposing a diabetes ohc framework for keeping patients connected to the program after discharge from the program. aghdam & watson , wellington towards empowering diabetic patients we collected data from the three popular reddit diabetes online communities (r/diabetes, r/type diabetes, and r/diabetes_t ). reddit is a popular forum for diabetes (duggan and smith ) . there are numerous health-related topics on this website, which make it a promising source of users' interactions for this research study. in addition, reddit allows researchers to mine its data. hence, we used the python reddit application programming interface (api) wrapper (praw) to collect the data. praw is a python package that allows researchers to access, parse topics and subreddit, and extract the associated reply threads. as inclusion criteria for selecting posts and threads, we selected type- diabetes-related topics with more than replies on each topic to obtain enough information. the interactions between users are mostly focused on the posts themselves and members will give the post all their attention. demographic information about the participants was anonymized to guarantee the confidentiality and privacy of participants' data. in every stage of this research study, we followed the code of ethics for researchers of the queensland university of technology (qut). the approval number is . in this study, we conducted an inductive thematic analysis to identify emergent themes from the data. the six steps of thematic analysis provided by (clarke et al. ) , guided us to identify the salient themes. following the six steps of the thematic analysis and with the assistance of the nvivo qualitative analysis software, we manually generated an initial list of codes. during the first step, we performed an initial analysis of the relevant topics and threads and recorded our notes via memo and annotation features of nvivo . in the second step, we inductively generated nodes. in the third step, we combined codes revealing three overarching themes and nine subthemes. in the fourth step, which was reviewing and refining the themes, we reviewed all themes and subthemes to make sure that they followed a coherence pattern. during this phase, two themes were integrated because of their common content. in the fifth step, we concisely named the identified themes to reflect the story behind each theme and reflect what the themes are about. hence, we named themes that address the research questions. finally, in the sixth step, findings were synthesised to provide a concise and coherent report. in terms of testing the trustworthiness of the findings, we employed percent agreement as our method of inter-coder reliability checking. two scholars, experienced in qualitative research and thematic analysis, checked different parts from creating initial codes to naming the themes. each of them independently analysed the entire data and during the first meeting, the per cent agreement was % and after the second meeting, discussing the essence of the themes, a consensus was achieved and the overall results were %, making us confident about the reliability of our findings. after performing the thematic analysis, our analysis resulted in three emergent themes from the data. themes include ( ) exchange lifestyle-related advice, ( ) experience of commonality, and ( ) brainstorm potential solutions for daily challenges. table , summarises the thematic analysis outcomes. as evidenced in table , patient participation in diabetes online communities leads to the co-creation of value. for instance, in theme , patients shared resources such as articles, and videos with peers. another key finding is to improve patients' psychological wellbeing by participating in online activities such as story sharing and encourage other members of the community in selfmonitoring. ohcs provide an opportunity for users to enhance their knowledge about symptoms, share their experience and advice. information sharing by peers, experience and advice sharing, life-style related advice sharing, and sharing daily-basis activities are the most common activities identified by researchers in this study through thematically analysing the content of threads in the reddit diabetes online communities. these types of giving and seeking (exchanging) advice are illustrative examples of value co-creation behaviours. in the value co-creation process, stakeholders such as organizations, patients or caregivers share, integrate and renew each other's resources ). our analysis shows that diabetic users mostly shared their experience, stories, and online resources (e.g., research articles, youtube videos, and websites' urls). resource exchange is a mutual action taken by stakeholders in ohcs to access, share, and integrate resources (beirão et al. ) . in this regard, ohcs can facilitate resource exchange among stakeholder. for instance, members of the diabetes communities shared their up-to-date information and experience about using wearable devices (e.g., continues glucose monitors (cgm), dexcom and sport watches) for self-monitoring their health condition and reduce the burden of living with diabetes and improve quality of life. the experience of commonality in ohcs provides opportunities for members to feel that they are not alone. hence, the experience of commonality is associated with positive mental health, improving emotional wellbeing members of the diabetes communities perceived these online platforms as great places to tackle the feeling of loneliness and isolation. especially in the current situation of the global outbreak of covid- , these online communities are ideal places to tackle psychological distress and depression. at this particular point in time, diabetic patients need to strengthen their sense of community by connecting and supporting each other in the ohcs. because of the nature of ohcs, aghdam & watson , wellington towards empowering diabetic patients which provides access to information and coordinated social interactions, the members of these communities benefit an alternative solution and needs such as improving their wellbeing (zhao et al. ) . emotional support directly impacts on the ability to self-manage diabetes and equally selfmanagement of diabetes influences emotional wellbeing (schiøtz et al. ) . sharing the same situation and stories with other members is another aspect of emotional support. sharing the same stories creates a shared sense of meaning and community for users. in the reddit diabetes communities, a large number of users encourage peers in their self-management of diabetes. patients also reported that sharing monitoring data such as blood glucose and weight makes them feel empowered and motivated. members of these communities' support each other in coping with social and emotional barriers, staying motivated to reach their goals, and encourage better self-care habits without fear of judgement or stigma. improving the emotional wellbeing of diabetes leads to better self-care, overcoming psychological barriers, and ultimately, a better quality of life. ohcs are ideal places for brainstorming solutions by members. we identified brainstorming of potential solutions to address daily challenges as another co-creation behaviour occurred in diabetes online communities. virtual brainstorming is one of the most significant benefits of ohcs for diabetic patients. it provides an opportunity for community members to contribute new ideas to address diabetic daily challenges such as carrying medical equipment, diabetic's workplace problems, injection, and sleep problems. this was identified in many threads posted by the members of the communities. hence, ohcs are ideal places to brainstorm potential solutions to address these issues. as it can be viewed in table , reddit patient suggests a solution to another patient, who is struggling with carrying diabetes bag in public and private business areas. these types of solutions are another example of value co-creation behaviour within diabetes online communities. participating of community members in brainstorming activities, make them feel that their contributions are valuable and their ideas will help peers to tackle some daily challenges. because of the high number of demands for dgep, patients need to be in a waiting list before joining the program. while they are in a waiting list, they can communicate with discharged patients and use their experience. the resource exchange help patients reduce their stress and better prepare for the program. during the program patients, share their experiences and health-related stories with peers, encouraging each other to reach their health-related goals. during this phase, ohc can play an important role as an online interactive platform to facilitate patient-to-patient and patient-to-hcp interaction. after discharge from the program, patients still need to stick to their plans and selfmanage their diabetes. ohcs provide opportunities for them to keep connected to the program, interact with hcps and share their experience of the program with patients, who are in the "prior-tojoining" phase. figure , demonstrates the proposed framework for diabetes online communities. aghdam & watson , wellington towards empowering diabetic patients in terms of the validity and utility of the proposed framework, we conducted expert interviews. a qualitative assessment of the framework flexibility was carried out through interviews with healthcare professionals and the diabetes program coordinator at the qut clinic. two health experts, who are directly involved and organised the dgep, and have more than ten years of experience in the healthcare domain initially evaluated the framework and provided their feedback and suggestions. ohcs are proper educational platforms that lead to better health outcomes and members can learn more from others on how to better manage their health conditions (chen et al. ). information that shared by patients in ohcs benefits other patients by learning from peers, improving their self-management of disease, and ultimately, improving their health (yan and tan ) . the proposed framework focused on patients as active agents in the process of online value co-creation. patients are pivotal stakeholders in our framework that can co-create value by resource exchange and social support. in our framework, diabetic patients participate in different forms of value co-creation through informational, social, and emotional support. ohcs empower patients to actively engage in co-creation activities / especially in times of fear, isolation, and uncertainty. this research study has been conducted during the global pandemic of the covid- . during this pandemic and isolation time, patients increasingly participate in diabetes online communities to gain and offer emotional support. these easy-access and / online platforms help patients to tackle psychological issues such as depression, anxiety, and loneliness because diabetic patients have a twofold greater risk of depression (schram et al. ). shared stories and experiences in ohcs make patients feel that they are not alone, strengthening their sense of community by connecting and supporting each other. digital health platforms such as diabetes online communities have the potential to increase easy access to diabetes self-management interventions and techniques in the lower cost (rosal et al. ) . furthermore, participating in diabetes group-based education program provides opportunities for patients to meet and discuss with other members of the communities, obtaining social and emotional support (steinsbekk et al. ) . in doing so, in recent years, the queensland university of technology (qut) offer a partnership program to patients who are newly diagnosed or living with the condition long term. this program aims to provide a quality lifestyle intervention and empowering type- diabetic patients to better manage their symptoms. as type- diabetes is a self-managed disease, one of the main aims of the program is to keep patients connected to the program after discharge. we australasian conference on information systems aghdam & watson , wellington towards empowering diabetic patients adopted customer-dominant logic (cdl) as a way to explore overlaps between our findings and the dgep. cdl is focused on activities and experiences of the customer at three different stages: preservice, service, and post-service (heinonen and strandvik ) . it is used as a way to extend the customers' perceptions of the offering and to extend market interactions (heinonen and strandvik ) . following cdl, we divided the diabetic patient journey into three phases including; ( ) prior to joining the program, ( ) during the program, and ( ) after discharge from the program. in each phase, we identified value co-creation behaviours such as; resource sharing, story and advice sharing, and social and emotional support. theoretically, we extended the target body of the knowledge in the healthcare service delivery through enhancing the empowerment theory in which, patients are the central facet and healthcare professionals and healthcare organisations are facilitators of the value cocreation process (funnell and anderson ) . research studies have overlooked the nuances relationship between empowerment theory, value co-creation, and the role of ohcs as facilitators for this process. this study provides an opportunity for leveraging peer-to-peer support within digital health platforms such as ohcs to empower patients in their self-management of diabetes. practically, our findings further provide recommendations to the healthcare industry on how to effectively contribute to the online intervention by shifting from traditional dyadic interaction between healthcare professionals and the patient to online co-creation among all stakeholders. we believe that healthcare providers can potentially use our theoretical and empirical findings to extend the value of the face-toface diabetes group-based education programs by keep patients connected to the program / regardless of their geographical distance with lower cost. our study is not without limitations, yet these limitations provide interesting avenues for future research. our data were gathered from reddit diabetes online communities. we selected three popular diabetes communities on the reddit to analyse the contents and interactions among members. we might overlook some small communities related to type- diabetes. furthermore, we only used reddit as our data collection source. future studies can focus on more diabetes online communities, aiming that how can a fully functional assistive artefact be designed for diabetic patients, using the design science research guideline (miah ; miah et al. ) . although the face-to-face diabetes education program held in queensland, australia, it can be generalised to any other organisational or country context (for example, in decision support implementation (ali, miah and khan, ) ensuring empowering end users). our future study will extend the current framework by conducting interviews with the members of the communities to identifying their current level of engagement with ohc, identify benefits and challenges of using these platforms, and investigate their online value co-creation behaviour. therefore, there are some areas required for further research. another future avenue is to investigate the perspective in which healthcare organisations indirectly participate in online value cocreation. experimental design studies of ohcs to explore the behavioural and psychological aspects of social support could also be useful. in this research study, we sought to extend the current understanding of the potential of diabetes online communities in empowering self-management for diabetic patients. as such, the main aim of this study was to investigate the potential practices of online diabetes communities to empower selfmanagement of diabetic patients in their health journey. findings show that patients in diabetes online communities share information, experiences, stories, and potential solutions. they actively participate in online activities regarding offering and receiving support from peers. the vast majority of the shared contents on diabetes online communities include lifestyle-related advice such as diet, exercise and using wearable technologies to better monitor and care of diabetes. members of diabetes online communities contend that these online forums are ideal platforms to obtain social and emotional support from peers. our findings, which investigated the connection between diabetes online communities' practices and outcomes and the real-world dgep case can further assist healthcare organisations to effectively contribute to the online intervention and extend their communication channel from a traditional power balance between hco and patients to interactive platform that enables all stakeholders to actively engage in value co-creation activities. as discussed, type- diabetes is a chronic disease that needs ongoing self-care and self-manage. ohcs provide opportunities for them to encourage each other in regards to sticking to their self-monitoring and selfmanagement. this is especially true when they discharge from the dgep and have no access to faceto-face interactions. the st annual crossing the quality chasm summit: a focus on communities improving the theoretical understanding toward patient-driven health care innovation through online value cocreation: systematic review online value co-creation 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self-management education (dsme) on glycemic control in patients with type diabetes digital health platform complementor motives and effectual reasoning group based diabetes self-management education compared to routine treatment for people with type diabetes mellitus. a systematic review with meta-analysis diabetes management through remote patient monitoring: the importance of patient activation and engagement with the technology an evaluation of a self-management program for patients with long-term conditions improving chronic illness care: translating evidence into action analyzing and predicting user participations in online health communities: a social support perspective feeling blue? go online: an empirical study of social support among patients patient value co-creation in online health communities: social identity effects on customer knowledge contributions and membership continuance intentions in online health communities empowerment theory this is an open-access article licensed under a creative commons attribution-noncommercial . new zealand, which permits non-commercial use, distribution, and reproduction in any medium key: cord- -wbfgrez authors: shi, chunhong; zhu, haili; liu, jun; zhou, jian; tang, weihong title: barriers to self-management of type diabetes during covid- medical isolation: a qualitative study date: - - journal: diabetes metab syndr obes doi: . /dmso.s sha: doc_id: cord_uid: wbfgrez purpose: diabetes self-management behaviors are necessary to obtain optimum glycemic control, reduce the risk of complications, and improve health outcomes. the covid- pandemic imposes an additional struggle for self-management by diabetes patients. although previous studies have reported socio-demographic, behavioral, psychological, and cultural barriers to diabetes self-management, little is known about perceived barriers to diabetes self-management among patients during isolation following their recovery from covid- . the purpose of this study was to explore perceived barriers among type diabetes patients during isolation following their recovery from covid- . patients and methods: a qualitative, exploratory, and descriptive research design was utilized. semi-structured telephonic interviews were conducted with patients with diabetes who had been discharged from one covid- designated hospital and underwent isolation in the designated facilities in wuhan city, hubei province, china. data were analyzed using colaizzi’s seven steps. results: barriers to diabetes self-management identified by patients with diabetes during isolation were categorized into five major themes: inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support. conclusion: perceived barriers to diabetes self-management described by diabetes patients indicated a lack of environmental resources and support strategies to meet their needs. efforts to remove barriers are important in assisting patients with diabetes to improve their quality of life and health outcomes. coronavirus disease (covid- ) , which was declared a public health emergency of international concern by the world health organization (who) on january , has posed a severe threat to global public health. , diabetes mellitus (dm) is a common chronic disease in china with a prevalence of . %. although people of all ages are generally susceptible to covid- , patients with diabetes are at higher risk for covid- due to the multiple concomitant chronic diseases and immunosuppression. , according to the currently published literature, the prevalence of dm among covid- patients and critically ill covid- patients were . - . % [ ] [ ] [ ] [ ] and %, respectively. the chinese center for disease control and prevention (china cdc) has stipulated that covid- patients discharged from hospitals are subject to a -day period of isolation and medical observation. as of midnight on august , , the total number of confirmed covid- cases had reached , in china. these facts indicated that a large number of covid- patients with diabetes underwent isolation after being discharged from hospitals. patients with diabetes recovering from covid- , who experienced the chronic hyperglycemic state and persistent inflammatory states, are at higher risk of covid- reinfection and the occurrence and progression of dm complications. there is a compelling need for this vulnerable population to reduce this risk through good blood sugar control during their isolation. however, ideal blood sugar levels cannot be maintained solely by anti-diabetic medications; good self-management behaviors play a crucial role in dm treatment-especially for those with type diabetes mellitus (t dm). self-management refers to long-term, and effective decisions and behaviors, to maintain patients' well-being, which involves medical, behavioral, and emotional management. positive and effective self-management not only alleviates the progression of dm on physiological indicators but also improves the patients' quality of life. scholars from stanford university pioneered the application of the concept and methods of self-management in a community-based diabetes self-management program. these early studies have opened new channels for the prevention, control, and treatment of dm and substantially improved the quality of life of patients with diabetes. promoting effective diabetes self-management has long been a challenging issue for the health systems, healthcare providers, community workers, and patients with diabetes. although the data regarding diabetes management for t dm patients recovering from covid- during isolation remain scarce, notably, previous studies have reported that among chinese t dm patients, only . %- . % have achieved optimal glycemic control (hemoglobin a c level< . %, mmol/mol) - and . %- . % have manifested good self-management behaviors. , this raises the issue of how to identify factors that hinder diabetes selfmanagement and to address these potential barriers. studies in developed countries such as the united states, canada, the united kingdom, and singapore have found that common barriers to self-management include poor communication between patients and healthcare providers, limited accessibility to healthcare facilities, lack of family support, inadequate disease knowledge and limited disease treatment methods, lack of motivation for change, physical and cognitive disorders, limited access to diabetes education, and financial barriers. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] evidently, factors that hinder diabetes self-management are complex and multifaceted. however, the barriers to diabetes self-management for patients with diabetes recovering from covid- during their isolation are not precisely known. to date, a considerable amount of literature on glycemic treatment and control in covid- patients with preexisting dm has been published. , most studies, however, focused on hospital and physician practice, while few studies investigated or mentioned self-management among patients with diabetes during their isolation following recovery from covid- . a qualitative study is an ideal design for an in-depth understanding of the feelings and experiences of patients with diabetes. such studies are of great significance to elucidate the perceived barriers to diabetes self-management among isolated patients. this study addressed a gap in this field by interviewing patients with diabetes subjected to medical isolation after recovering from covid- to gain a deeper understanding of the barriers to diabetes self-management, and provide new perspectives and approaches for the design of interventions and formulation of policies. this study adopted a descriptive qualitative methodology to collect data through telephonic interviews, which provided a rich and thick description of the participants' perceptions of barriers to diabetes self-management. a phenomenological approach was used to achieve an indepth understanding of the factors hindering diabetes selfmanagement from the patient's perspective. participants were recruited through purposive sampling based on the following inclusion criteria: ( ) t dm patients with a disease duration of greater than year, ( ) covid- patients with diabetes after being discharged from the hospital, ( ) had stayed at designated isolation sites for at least days, ( ) spoke and understood chinese (mandarin), and ( ) agreed to participate in the study. patients with type dm or younger than years old were excluded. the primary researchers of this study, who were nurses at a designated covid- hospital in wuhan city, hubei province, china, contacted patients who met the inclusion criteria through the contact information listed on their medical records. the sample size was determined by data saturation-when no new information was obtained during the last two interviews. variations in age, education level, and duration of diabetes were considered to ensure diversity in the perception of barriers to self-management. we followed the consolidated criteria for reporting qualitative research to report the findings of this study. semi-structured, in-depth telephonic interviews were conducted from february to march , , at a convenient time after dinner (approximately : - : beijing time) in a quiet and comfortable environment. before each telephonic interview, the primary researchers explained the objectives and methods of the study to the participants, promised to perform confidentiality measures, and obtained verbal informed consent from all participants. all interviews were recorded using a cellphone and a recording pen (newsmy v , gb internal memory) with the consent of the participants. an interview guide (table ) was used to conduct the interviews, which consisted of a series of open-ended questions regarding the various aspects of self-management. the interview guide was tested using pre-interviews with two patients of diabetes not included in the actual study, which resulted in corrections of the language and content. during the formal interviews, the interviewees were encouraged to express their thoughts and perceptions thoroughly and probing questions, such as, "can you please elaborate on this?" were included to increase the depth of the discussion. the nonverbal information (eg, tone of voice, pause) and the important statements stressed by the patients were documented during the interview. each interview lasted between and minutes. each audio recording was transcribed by a co-author within hours of the interview and reviewed by another author who interviewed the patients to ensure accuracy of the transcript. the interviews, raw transcripts, and data analysis were conducted in mandarin chinese. data analysis was conducted by two co-authors using colaizzi's seven-step method to extract themes and sub-themes. the detailed steps were as follows: ( ) reading and re-reading raw data transcribed from the audio recordings; ( ) marking and extracting significant statements pertaining to the investigated phenomena; ( ) coding recurrent important viewpoints; ( ) summarizing all coded viewpoints; ( ) elaborating and articulating the meanings of the viewpoints; ( ) integrating, categorizing, and refining similar viewpoints into themes; and ( ) returning the formulated themes to the interviewees for validation. all authors agreed with the data analysis results. to ensure the rigor of the study, the four criteria of dependability, credibility, transferability, and confirmability were in this study, participants were interviewed. table shows the demographic information of the participants. barriers to diabetes self-management were categorized into five themes: inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support, as indicated in table . respondents in the study were found to have poor knowledge, inadequate self-care behavior and low-level beliefs regarding diabetes self-management. the theme "inadequate knowledge and behavioral beliefs" emerged from all discussions that contained three sub-themes, namely, limited diabetes knowledge, confusion about taking medications, and low adherence to self-monitoring of blood glucose. most participants (n= ) alluded to the fact that inadequate diabetes knowledge challenged their management of blood glucose. they often asked for help from those around them (eg, daughter or father). they had limited knowledge regarding diet management and physical exercise. some of them even believed that refraining from sweets and carbohydrate-rich foods or insisting on physical exercise alone could achieve good glycemic control. one female patient stated, "my knowledge regarding diabetes has been gained from my daughter, who is a nurse. she told me which foods i can or cannot eat." (p ) another male participant stated, "my dad also has diabetes. he controls this disease through exercise and obtains good outcomes, so i control my blood glucose by exercising." (p ) a similar view was expressed by another patient, "i know a little about diabetes. i pay little attention to it in daily life and just engage in exercise to control my glucose." (p ) all participants voiced their concerns about medication treatment. more than half of the patients were unfamiliar with the use of hypoglycemic agents. they were confused about taking medications, with most uncertainty involving the names, usage and side effects of the medications, which prevented participants from effectively managing their disease. a female patient expressed unfamiliarity with the usage of hypoglycemic agents: i am worried whether i take too much acarbose. i take two tablets with each meal, and i do not know if it is too much . . . the doctor told me to alternate between metformin and acarbose, which made me confused. (p ) a male patient stated, the hypoglycemic medicines prescribed by the doctor when i was discharged from hospital were different from what i used at home; maybe the effects are the same. i do not know whether these medicines are better or worse than the previous ones, i cannot judge them. (p ) low adherence to self-monitoring of blood glucose among all patients, only one brought test strips and needles to the isolation site. they paid little attention to blood most of the isolation facilities were converted from hotels or high school premises at short notice in response to the demand during the covid- pandemic period. the shortage of resources at these facilities was another issue discussed by all patients. this theme consisted of four subthemes: limited space for exercise, unavailability of blood glucose monitoring, absence of a diabetic diet, and undersupply of hypoglycemic medications. at the isolation sites, the participants were largely confined to their rooms because of social distancing policies. all participants described that they exercised daily but could only do so in their rooms or corridors. as a male patient's transcripts showed, regular blood glucose monitoring is essential for glycemic control in diabetes. among all interviewees, only one had performed daily blood glucose monitoring; the remaining participants mentioned that they had not monitored their blood glucose at the isolation sites due to the unavailability of blood glucose monitoring. an elderly female patient stated, all participants were concerned with diet, which is a crucial tool for managing t dm. , in particular, participants clearly expressed that the diet provided at the isolation sites was unsuitable for patients with diabetes. as stated by participant , "many food items at the isolation site contain sugar . . . i have no choice but to avoid food items with sugar . . . there is no diabetic diet." (p ) another female patient further added, approximately half of the participants faced issues regarding the shortage of hypoglycemic medications, or medication changes, due to the non-supply of medications at the isolation sites. one participant mentioned, another female patient stated, "the medicines prescribed by the hospital are not enough, i don't know if they can last till the end of the isolation period" (p ). the participants described that they experienced hyperglycemia, physical discomfort, and insomnia during the mandatory isolation after contracting covid- , which discouraged them from self-managing the diabetes and reduced their motivation to self-manage their diabetes. suffering from health problems is an important obstacle to adherence to self-management behavior. two thirds of the participants stated that their blood glucose levels increased and became difficult to control after contracting covid- . the unsteady blood glucose made them feel frustrated and impeded their self-efficacy in their journey of diabetes management. as described by one participant, the elevation of blood glucose after contracting covid- was also mentioned by another female patient. "after getting covid- . . . my blood glucose was above [mmol/l]. it has never been so high over the last -odd years." she continued, "blood glucose is difficult to control; i can hardly manage it well." (p ) of note was that half of interviewees still experienced physical discomfort after covid- treatment and hospital discharge such as tiredness, shortness of breath, aches and pains, or a headache. these physical symptoms prompted them to focus on covid- recovery and treatment while ignoring the self-care of diabetes. another patient also experienced physical discomfort. nearly half of the participants experienced insomnia at the isolation facilities as they were unaccustomed to their isolation environments, subjected to activity constraints, and engaged in fewer social activities. insomnia led to their fatigue, poor concentration, and tension during the day and disrupted their diabetes management routine. the following examples demonstrated this experience. high contagious infectivity, potential fatality of covid- , loneliness in the isolated room, and difficulties in maintaining blood glucose levels elicited negative emotions in the participants. three quarters of patients with diabetes expressed unpleasant or unhappy emotions toward covid- and the isolation environment. such emotions can cloud their judgments and reduce rationality in decision-making on self-management behaviors. negative emotions as a barrier to self-management, emerging from the transcripts, included three sub-themes: stigma, dissatisfaction, and anxiety. participants may have perceived stigma for suffering from covid- . they feared discrimination from others and avoided full disclosure about their disease to both peers and healthcare workers, thereby influencing the way they view the disease and approach their self-management. a female patient expressed, the isolated patients faced various inconveniences at the isolation sites. some of them complained about the lack of supplies (especially medications) and expressed dissatisfaction with the living conditions and diets provided at the sites. dissatisfaction affected their activation of diabetes self-care and discouraged their behaviors toward diabetes self-management. one participant complained, "the isolation site offers nothing just serves for isolation . . . there's no fruit, no medicine . . . there are too many difficulties for us to manage diabetes." (p ) a male participant expressed his dissatisfaction toward the isolation site, this place isn't as good as the hospital, the room is really tiny . . . the (medical) service here (isolation site) isn't so professional compared with the hospital . . . i just try to control my blood sugar by eating less food. (p ) patients with diabetes often felt stressed and worried about the medication, diabetes supplies, and blood sugar levels. a third of the patients expressed that they were somewhat worried or anxious. this emotional distress often brings about negative consequences for diabetes and further affects their self-management behaviors indirectly. a participant stated, most patients with diabetes who underwent forced isolation perceived a lack of guidance and support. these patients described their experiences as a struggle to trudge along a difficult path of diabetes self-management, as they were unable to seek help from anyone under the constraints of social isolation. lack of support as a theme was expressed by most respondents, which had two subthemes: lack of professional guidance, and lack of family support. most healthcare providers at isolation facilities had been temporarily extracted from various healthcare departments, who might have had little diabetes knowledge and only took responsibility for covid- prevention and education. the participants expressed the view that they felt helpless with regard to managing their diabetes without professional guidance. for instance, a participant stated, "every morning, [healthcare providers] only ask if we feel comfortable and measure our body temperature . . . blood glucose is not monitored at the isolation site." (p ) another patient complained that "the doctors here show little concern for us . . . the healthcare providers differ from those at the hospital in terms of professional levels." (p ) the covid- isolation policy prohibits face-to-face visits from family members, which greatly affects the patient's access to family support. in addition, covid- is characterized by familial aggregation, which also reduced the sources and types of family support provided to the participants. as stated by a divorced female participant, during the isolation period, i have made no phone calls to my family and friends . . . my family members are also staying at the isolation sites, so it is too inconvenient . . . another participant expressed that she could not get actual assistance from her family members as they could only express their concern over the phone, "the concern from my family is of no use . . . sometimes they can't even send things to me because non-staff entering the isolation site is forbidden." (p ) this exploratory and descriptive qualitative study reported the barriers to self-management of t dm patients who had recovered from covid- during medical isolation. five major themes were identified: inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support. self-management is essential for prognosis and glycemic control in patients with t dm. understanding the barriers to self-management will help patients make changes and better manage their diabetes. our results showed that limited knowledge regarding dm is a major barrier to diabetes self-management. participants tended to gain diabetes knowledge from the experiences of people around them. the common assumption was that low educational levels (average below high school) and old age (mean age: . ± . years) limited their abilities to acquire medical information and seek better healthcare resources. similarly, studies conducted in ethiopia and iraq have indicated that a lack of appropriate information/knowledge hinders self-management among patients with diabetes. a study by ji et al showed that diabetes knowledge is positively correlated with overall self-management behavior. specifically, the higher the level of knowledge on diabetes, the better the self-management behavior of patients with diabetes. additionally, most patients also expressed their confusion about taking medication. low education and lack of diabetes knowledge might provide a possible explanation for this. previous studies have indicated that difficulties and frustrations in taking medications prevented diabetes patients from effectively self-managing. in addition, low adherence to self-monitoring of blood glucose posed another barrier to diabetes self-management, which was consistent with the findings of tewahido et al and mikhael et al. this is more commonly associated with the patients' economic position, fear of needles, the erroneous belief that blood glucose will remain normal with timely medicating, physical activity, and dietary modifications. a study by ji et al also demonstrated that blood glucose monitoring was the lowest priority of patients with diabetes when compared to medications, diet, and physical activity. the results of this study emphasized the importance of improving self-management knowledge and behavioral beliefs in patients with diabetes. efforts directed toward practical and person-centered diabetes selfmanagement education and support programs are necessary to improve patients' knowledge and behavioral beliefs and self-management levels. a shortage of resources was frequently identified as the key factor that inhibited diabetes self-management in this study. issues such as limited space at the isolation sites, unavailability of blood glucose monitoring resources, absence of a diabetic diet, and undersupply of hypoglycemic medications, were repeatedly mentioned by the participants. for instance, some participants expressed that the standardized diet at the isolation sites led to the inability to perform self-management in accordance with their specified nutrition plans. this finding was consistent with previous findings that residing in a community with limited healthy foods and the absence of safe exercise environments may be an important barrier to diabetes self-care and glycemic control. , for all participants in this study, the provision of resources needed for diabetes selfmanagement by the isolation facilities was a significant issue. however, as was widely recognized, the locations used for isolation of covid- patients had a unified layout and lacked the facilities conducive to diabetes selfmanagement. this finding suggests that creating a favorable environment for self-management of chronic diseases at the isolation sites, such as the provision of a diabetic diet and blood glucose monitoring as part of a daily health management program, is extremely important for the improvement of the quality of life and health of patients. suffering caused by the disease was a great barrier that emerged from the transcripts. this is consistent with the findings of hu et al, in which patients' physical suffering kept them from properly managing their disease. moreover, the results of the present study provided additional evidence that covid- may result in elevated blood glucose levels, which was congruent with the findings reported by ilias et al and brufsky. persistently high blood glucose may cause frustration in patients, thereby affecting their passion towards self-management. five participants in this study stated that they suffered from severe insomnia. in keeping with our findings, xue et al also reported significant sleep problems (eg, difficulty falling asleep, early awakenings) in the forced isolation population. in addition, poor sleep quality has been found to be significantly associated with decreased adherence to dietary, lower self-care adherence, and poorer diabetes control. given disease related suffering, it is imperative for healthcare and covid- isolation organizations to develop and implement strategies to deliver continuous care for discharged covid- patients, especially those with diabetes. negative emotions were discussed as a psychological barrier to self-management. half of the participants felt stigmatized, which was mainly manifested as societal rejection; one-third complained about poor service at the isolation sites, and one-third expressed anxiety. although the public health response to covid- has been essential in preventing and containing the epidemic, it may also have aggravated the stigmatization of patients. , forced isolation and the associated measures have disrupted the social lives of patients with diabetes, resulting in them feeling fearful and trapped. armitage et al reported that social isolation exposes older adults to greater risks of negative emotions such as depression and anxiety. an online study conducted in italy reported that longer isolation times, combined with smaller physical spaces, led to a deterioration in mental health. moreover, psychological distress affected the medication adherence and self-management of patients with diabetes. kato et al found that the nonadherence behaviors of patients with diabetes may be a response to the internalization of stigma. self-stigma is a negative independent factor that affects the self-care behavior of patients with t dm. our results confirmed these findings and suggested that greater emphasis should be placed on the mental health of this vulnerable population, and healthcare and covid- isolation organizations should adopt multifaceted strategies to eliminate potential drivers of negative emotions in isolated patients. this study revealed that the lack of professional guidance from healthcare providers (eg, self-care measures, maintenance of target blood glucose, monitoring of complications) is a common barrier to diabetes selfmanagement. healthcare providers play a unique role in delivering person-centered diabetes self-management education, supporting interventions, and assisting patients to undertake protective self-care behaviors. other qualitative studies have reported similar findings whereby patients with limited resources were particularly challenged when seeking medical services or obtaining care and support. , apart from the scarcity of guidance from healthcare providers, the participants also identified the lack of family support as another barrier to diabetes selfmanagement. during the isolation period, it is difficult for diabetes patients to obtain knowledge, care, and material support from their family members, although this support was essential for promoting lifestyle changes and improving self-management behavior in patients with diabetes. such a result matches the findings of previous studies, which considered family members, friends, and peers of patients with diabetes as primary promoters of selfmanagement. , , similarly, quantitative studies have also indicated that a higher level of social support is associated with better adherence to recommended selfmanagement behaviors. [ ] [ ] [ ] in conclusion, there was insufficient support to encourage diabetic selfmanagement of the isolated patients. such problems may be resolved by establishing electronic blood glucose records and a remote consultation system to provide practicable diabetes self-management education and support, and by enhancing telephonic and internet-based family support. this study had several limitations. first, we obtained data from a small geographical area (wuhan city) and a small, convenient sample ( patients with diabetes), which might limit the generalizability of the findings. second, our analysis was based on interview data. therefore, it was impossible to explore the differences between the demographic characteristics (such as gender and education level) of the barriers to diabetes selfmanagement. third, this study explored barriers to diabetes self-management from the patients' perspectives, without considering the experience of healthcare providers and family members. fourth, qualitative studies have inherent limitations, such as the tendency for subjectivity during data analysis. future research should collect data from larger samples or adopt a multicenter approach to obtain a broader view of barriers to diabetes self-management. our findings provide insight into barriers to diabetes selfmanagement among t dm patients during isolation following recovery from covid- . we found that inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support were barriers to self-management among patients with diabetes. understanding these barriers is beneficial for the formulation of targeted strategies, such as creating favorable isolation environments, strengthening medical and social support, and implementing patient-centered diabetes care, to promote successful self-management. at present, as many countries around the world are still in the critical period of pandemic prevention and control, greater concern should be paid to patients with diabetes during isolation. in addition, open dialogue among patients, healthcare providers, family members, and policy makers can be established to better support patients' diabetes journey and improve health outcomes. this study was approved by the ethics committee of hunan academy of traditional chinese medicine affiliated hospital (approval no. - ). we explained the objective, process, and methods of the study to the participants and obtained verbal informed consent prior to each telephonic interview. participants were assigned anonymous identification numbers (p , p , etc), and personally identifiable information was deleted from the transcripts to protect patient privacy. the interview data were kept strictly confidential, and all audio recordings and transcripts were stored in a passwordprotected computer. interviewees were free to withdraw from the study at any time without any reason. pneumonia of unknown etiology in wuhan, china: 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original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication. the manuscript management system is completely online and includes a very quick and fair peer-review system we would like to express our gratitude to the hunan academy of traditional chinese medicine affiliated hospital for the approval and support of this study and all participating patients for providing valuable information regarding barriers to the self-management of dm. furthermore, we wish to express our gratitude to the hunan academy of traditional chinese medicine for providing financial and material support. finally, we thank our advisors dr. chunyan li and dr. yinhua zhang for their contribution of valuable insights in the process of this study. the authors report no conflicts of interest in this work. key: cord- - oxtlzqo authors: cristelo, cecília; azevedo, cláudia; moreira marques, joana; nunes, rute; sarmento, bruno title: sars-cov- and diabetes: new challenges for the disease date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: oxtlzqo a novel small enveloped rna virus with the typical characteristic of the family to which it belongs, a crown, hence the name coronavirus, appeared in december in wuhan, china, and subdued the world to its influence. the particular severity of the disease and higher mortality rates in patients with associated morbidities, including hypertension, obesity and diabetes, increases the concern over the consequences of this pandemic. in this review, the features of sars-cov- will be addressed, as well as the reasons why it poses a particular challenge to diabetic patients. we will also highlight the recent treatment strategies being explored to control this pandemic. emerging evidence demonstrates that the correct management of diabetes in those patients infected with sars-cov- is of utmost importance for the viral disease progression, therefore, the importance of blood glucose control will also be addressed. sars-cov- shares % homology with bat sars-like-covzxc , % with human sars-cov and around % with middle east respiratory syndrome coronavirus (mers-cov) [ ] . as all the other coronaviruses, sars-cov- comprises the four structural proteins e (envelope protein), m (membrane protein), n (nucleocapsid protein) and s (spike protein), as well as eight accessory proteins [ ] . the spike surface glycoprotein plays an essential role by promoting the attachment of the virus to its receptor on host cells and may determine its host tropism and transmission ability. receptor-binding domain (rbd) of s-protein from sars-cov- shares identical d structure with the rbd of s-protein from sars-cov, as well as . % amino acid sequence homology [ ] . in vitro and in vivo studies showed that angiotensin-converting enzyme (ace ) is the cellular receptor for sars-cov virus [ , ] . the novel sars-cov- also binds to ace [ , [ ] [ ] [ ] with to times higher affinity than sars-cov does [ ] . in addition, sars-cov- employs the cellular transmembrane serine protease (tmprss ) for s protein priming, allowing internalization and replication in the host cells [ ] . ace is a naturally occurring enzyme abundantly present in humans, mainly in the cell membrane of lung alveolar epithelial cells [ ] [ ] [ ] [ ] and enterocytes of the small intestine [ ] , which provide as entry routes for the sars-cov infection and probably sars-cov- . additionally, ace is also expressed by arterial and venous endothelial cells and arterial smooth muscle cells [ ] , cholangiocytes [ ] , testis [ , ] , pancreas [ , ] , in cardiovascular [ , , ] , renal [ , , ] , urothelial [ ] , mucosal [ ] and gastrointestinal tissues [ , ] in minor extent. ace is homologous to the firstly discovered ace , and both enzymes are part of the reninangiotensin system (ras), which has a crucial role in regulating blood pressure, maintaining electrolyte and fluid homeostasis for its potent vasoconstrictor/vasodepressor actions [ ] . ras is an enzymatic cascade starting with the cleavage of angiotensinogen by renin to form angiotensin (ang) i. this peptide is then further metabolized by ace , which removes two amino acids at the c-terminal end to form the potent vasopressor peptide ang ii [ ] . ang ii levels are endogenously regulated by the ace , which is a membrane-bound monocarboxypeptidase that cleaves the terminal leucine and phenylalanine residues from ang i and ang ii originating ang - and ang - , respectively. the hexapeptide ang - exerts a potent vasodilator, anti-fibrotic, anti-proliferation and anti-inflammatory effect via activation of its mas receptor. its effects counterbalance the ace -ang ii-atr system [ ] . on a similar manner, ace inhibitor drugs (aceis) have an antihypertensive effect and substantially lower the risk of death, heart failure and stroke [ ] . patients with hypertension and diabetes benefit from the use of these drugs, since not only ace is insensitive to blockade by ace inhibitors, but also, the use of these inhibitor drugs increases the ace gene expression and activity, probably due to an accumulation of ang i [ ] . ace has been found to have protective effects against lung injury in different lung injury animal models [ , , ] . specifically, in diabetes, ace seems to have a protective role in the progression of cardiovascular and renal complications and has been suggested as a potential therapeutic target for the management of diabetes and its complications [ , ] . studies in mice showed the role of ace in the improvement of glycemia levels in mice with diabetes by direct effects in the pancreas [ ] , improving insulin sensitivity and glucose-mediated insulin release [ ] and reduction of the risk of type diabetes development [ ] . the effect of diabetes in the expression of ace is not well established. studies in animal models of diabetes evidenced either an increased or reduced expression of ace in renal tissues and pancreatic tissues, depending on the disease stage. on contrary, the levels of ace in lung tissue of mice with diabetes seem to be lower when compared to renal and pancreatic tissues [ , ] . similarly, a study in non-obese diabetic (nod) mouse model showed an increase of ace in serum, liver and pancreas, but not in the lung [ ] . a study performed in by soro-paavonen et al. showed increased serum ace activity in type diabetes mellitus (dm) patients with vascular complications but not in those without complications [ ] . it has been found that aceis and angiotensin ii receptor blockers (arbs) cause an overexpression of ace in patients treated with these drugs [ ] . in the study of soro-paavonen, patients treated with aceis had increased ace activity, independently of the presence of vascular complications [ ] . however, the expression of ace mrna was not measured. expression levels of ace have been associated with susceptibility to sars-cov and sars-cov- infection in different cell lines [ , , ] , therefore, raising the concern that patients being treated with aceis or arbs could be at higher risk of infection and of associated morbidity and mortality after a sars-cov- infection, due to a higher expression of the virus' entry gate in target tissues [ ] . nevertheless, conflicting information has been found on this topic and some data suggest that aceis and arbs can have protective effects against lung injury [ ] . with relatively few clinical studies on this matter, when compared to the preclinical studies in animal models, it may be erroneous to admit that the effects of ras inhibitors on ace expression are translatable to human physiology. additionally the measurements of ace plasma levels, performed in most studies, may not be a reliable indicator of ace activity, since the full length protein is predominantly membrane bound [ ] . taking advantage of ace , sars-cov- gains access to the cells, however it has been shown that soon after infection ace expression is rapidly downregulated [ ] . whether this effect is caused by the virus, to prevent ace protective effects [ ] , or results from an indirect mechanism is not yet clear. it has been confirmed in some clinical studies that the long-term use of aceis or arbs by patients is not associated with an increased risk of sars-cov- infection, neither of developing severe covid- or even with a higher risk of in-hospital death [ ] [ ] [ ] . all these studies highlight that the withdrawal of these medications is not recommended to prevent serious covid- , since these have well-known benefits in protecting the kidney and myocardium, [ ] with the clinical decompensation caused by its removal potentially causing a more serious condition than the viral infection. the multi-organ damage is characteristic of sars, nevertheless the major affected organs include the lungs, heart and kidney. the severity of disease progression and death predictor factors include old age, thrombocytopenia, severe hypoxia and hyperglycemia [ ] . hyperglycemia can also be a consequence of the sars-cov infection, due to the ace dependent damage of pancreatic islets and exocrine tissue, as islet damage, elevation on fasting plasma glucose levels and diabetes development during hospitalization have all been reported [ ] . although the pancreas damage was transient to most patients, in some cases diabetes remained after -years follow-up [ ] . in the case of sars-cov- the same transient damage in the pancreas has already been documented [ ] , and given its higher infectivity and affinity for the ace receptor, there is increased concern relative to the complications caused by hyperglycemia, as well as the long-term effects of the infection on recovered patients. hyperglycemia is characteristic of diabetes, when this chronic metabolic disorder is left untreated, which leads to serious complications ranging from limb amputations, kidney failure, blindness or cardiovascular disease [ , ] . this disorder may be caused by insufficient insulin production by the pancreas, resistance to insulin action or a mixture of both [ ] . therefore, as hyperglycemia underlies many of the complications developed in the disease course, a tight control of glucose blood levels in patients with diabetes is essential. since the beginning of covid- outbreak, diabetes has been reported as one of the high-risk factors for rapid disease progression and bad prognosis of covid- [ ] . for instance, a retrospective cohort study with chinese patients infected with sars-cov- showed that % of the patients had a comorbidity, with diabetes representing % of those patients [ ] . another study showed that among deaths due to sars-cov- in wuhan, . % had diabetes [ ] . also, a different cohort study analyzing patients from wuhan with confirmed covid- pneumonia revealed that . % of the patients had diabetes. they also observed that among the patients who developed acute respiratory distress syndrome (ards) ( . % from the total cohort), more patients had comorbidities than those who did not develop ards, being diabetes the second most frequent comorbidity ( . % in ards-patients versus . % in non-ards patients) [ ] . furthermore, the largest case series of covid- in china, reported by the chinese center for disease control and prevention, showed that dm patients had higher mortality rates ( . %) when compared to overall population ( . %) in a total of , analyzed cases [ ] . this comes as no surprise, as it is reported that people with diabetes demonstrate higher susceptibility to several infectious diseases, such as tuberculosis, pneumonia or influenza [ ] . the underlying mechanisms are not completely understood and depend on the type of infection, but some hypotheses have been raised. some possible explanations for dm being a high-risk factor for covid- may be due to hyperglycemic environment, which is known to increase the virulence of some pathogens. besides, it was also reported that phagocytosis and chemotaxis are impaired, the production of interleukins in response to infection is reduced, as well as the response of t cells and neutrophils [ , ] . overall, the immune response, which is vital to fight against covid- infection, is impaired, especially in diabetic patients with poor blood glucose control. furthermore, several studies have shown that dm patients have a significant decrease in forced vital capacity (fvc) and forced expiratory volume in one second (fev ), which are important indicators of lung function. this impaired pulmonary function was significantly associated with poorly controlled diabetes and consequently hyperglycemic levels [ ] [ ] [ ] . therefore, this reduced pulmonary capacity may also increase susceptibility to respiratory infections, possibly representing another factor in the myriad of events that might increase the vulnerability of dm patients towards covid- . in the absence of a specific antiviral drug, physicians are considering and trying lopinavir, ritonavir, interferon- b, rna polymerase inhibitor, remdesivir and tamiflu that were already reported for other diseases [ ] . inclusively, zinc oxide nanoparticles have also been considered, since they were shown to have inhibitory effects on h n viral load [ ] . plus, vitamin c is also a good supplement for the immune system and has some preventive effects on pneumonia [ ] . however, none of these have shown yet evidences of being beneficial for covid- . as mentioned, it is suggested that therapeutics for diabetes and hypertension, namely aceis and arbs, are responsible for upregulating ace . on the other hand, this is the functional receptor that sars-cov- uses as cellular entry [ ] . in this sense, some authors hypothesize that these therapeutics may contribute for the increased infection and advice to discontinue aceis and arbs, used in patients with diabetes or hypertension. however, there is no clear evidence in animals nor humans confirming this theory. besides, ace can also be increased by thiazolidinediones and ibuprofen, as well as exercise and dehydration. plus, it was very recently published a chinese study showing that transplantation of ace -mesenchymal stem cells improves the outcome of patients with covid- pneumonia [ ] . some studies have actually already shown that overexpressed ace plays a protective role in the lungs with sars-cov- infection, suggesting arbs and aceis as therapy [ , ] . as proof, in a preclinical study, authors injected animals with the spike glycoprotein of sars-cov, to cause a severe lung injury and verified that ace is significantly downregulated. after treating them with arb losartan, the severe acute lung injury was attenuated [ ] . this evidence was supported by findings from china, where they showed that ace blockade resulted in exacerbated lung damage and reduced animal survival after respiratory syncytial virus infection [ ] . actually, there is a comment from an israel author, published in early march, proposing arbs and aceis as a treatment for patients with covid- infection to reduce the risk or severity of viral pneumonia [ ] . however, when the coronavirus spike protein binds to ace , there is a downregulation of ace , which leads to an excessive accumulation of angiotensin ii (vasoconstrictor, pulmonary inflammation, fibrosis, edema) and less ace to convert it to angiotensin - (vasodilator, anti-proliferative, cytoprotective). the big question here is to know who wins this battle: the virus that binds to ace , which is upregulated in lungs, or the protective effects caused by the ace upregulation. and this is not clarified yet. in this sense, european medicines agency (ema) recommend that treatment with arbs and aceis should be maintained in patients with diabetes and hypertension [ ] . patients who stop taking them may face more complications regarding kidney failure and increased mortality. either way, as an alternative treatment, calcium channel blockers (ccbs) can be used, since they seem not to increase ace expression and activity [ ] . commonly, and according to standard procedure, very sick patients should stop taking metformin and sodium-glucose transporter inhibitors, due to their adverse side effects, as acidosis and fat metabolism [ ] . in addition, the glucagon-like peptide receptor- analogues can also be stopped, since they may cause nausea, vomiting, and pioglitazone, among other side effects described elsewhere [ ] . plus, aromatase inhibitors should also be stopped since they reduce insulin sensitivity and insulin should be the only one used in acutely sick patients or with severe breathing disorders [ ] . only when recovered or stabilized, noninsulin therapy can be introduced. knowing that the virus infection is a multistep process, there are some possible targets to treat covid- . a strong candidate that could exert a potent antiviral effect is the anti-malaria chloroquine. it is described that the virus processing and internalization is facilitated by low ph and ph-dependent endosomal cysteine protease cathepsins [ ] . chloroquine becomes entrapped in membrane-enclosed low ph organelles and is rapidly protonated and concentrated in endosomes, interfering with their acidification. hydroxychloroquine has been then considered for short-term treatment trials [ ] . the antiviral activity of chloroquine combined with azithromycin against covid- in vitro was recently reported. however, the authors found no evidence of a strong antiviral activity or clinical benefit of this combination for the treatment of hospitalized patients with severe covid- . either way, ongoing randomized clinical trials with hydroxychloroquine should provide a definitive answer regarding the alleged efficacy of this combination and will assess its safety [ ] . also, amiodarone has the ability to interfere with the endocytic pathway, being suggested as a possible inhibitor of the sars coronavirus [ ] . after binding to ace , the virus requires the essential serine protease, tmprss , for s protein priming. so, using tmprss inhibitors (e.g. camostat mesylate), already used to treat cancer and hepatitis, can be a possible or adjuvant therapy [ ] . according to ema, the potential treatments that are in clinical trials are: remdesivir (investigational), lopinavir/ritonavir (anti-hiv), chloroquine and hydroxychloroquine (antimalaria and rheumatoid arthritis), systemic interferons as interferon beta (multiple sclerosis) and monoclonal antibodies with activity against components of the immune system [ ] . plus, all the diagnostics, treatments and vaccines considered for covid- are summed up in artis ventures platform [ ] . overall, the chance of developing serious complications due to sars-cov- infection is higher in people with more health conditions associated. as discussed above, diabetes and all the complications associated with this disease, such as weakened immune response or hyperglycemia, present a higher risk for infected patients (figure ) . not only for the covid- progression, but also as a higher risk to develop secondary infections and therefore worsening of the health state. for those reasons, an effective and tight management of diabetes, specifically of glucose plasma levels, is extremely important in infected patients with diabetes. additionally, while the use of aceis and arbs in sars-cov- infected patients has raised some questions regarding their beneficial or harmful effects on disease progression, there is not enough evidence yet that allows drawing conclusions on this issue. therefore, while care must be taken in the use of these drugs, their abrupt withdrawal is not recommended as it could lead to even more serious complications. several strategies are being tested to control the covid- pandemic and a better understanding of the sars-cov- effects on high-risk patients is fundamental to decrease the morbidities and mortality. european centre for disease prevention and control. situation 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in times of covid- epidemic inhibition of h n influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine vitamin c intake and susceptibility to pneumonia transplantation of ace -mesenchymal stem cells improves the outcome of patients with covid- pneumonia inhibitors of ras might be a good choice for the therapy of covid- pneumonia the vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases european medicines agency. ema advises continued use of medicines for hypertension, heart or kidney disease during covid- pandemic calcium-channel blockers for treatment of diabetic nephropathy an update on sodium-glucose co-transporter- inhibitors for the treatment of diabetes mellitus. current opinion in endocrinology adverse effects of glp- the review of diabetic studies aromatase inhibition reduces insulin sensitivity in healthy men should covid- concern nephrologists? why and to what extent? the emerging impasse of angiotensin blockade chloroquine is a potent inhibitor of sars coronavirus infection and spread no evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe covid- infection amiodarone alters late endosomes and inhibits sars coronavirus infection at a post-endosomal level sars-cov- cell entry depends on ace and tmprss and is blocked by a clinically proven protease inhibitor update on treatments and vaccines against covid- under development fight the pandemic this work was financed by feder -fundo europeu de desenvolvimento regional funds through the compete -operacional programme for competitiveness and key: cord- -rqlfnywm authors: bloomgarden, zachary title: does glycemic control affect outcome of covid‐ ? date: - - journal: j diabetes doi: . / - . sha: doc_id: cord_uid: rqlfnywm nan diabetes is associated with adverse outcome of coronavirus disease . in a whole-population study of a uk data set of > million persons, approximately % had diabetes, but of in-hospital covid- -related deaths in this population, . % were of people with diabetes, with mortality rates among persons those with type and type diabetes approximately -fold and -fold greater than that in the nondiabetic population; with adjustment for age and other risk factors, type and type diabetes were associated with near tripling and doubling of mortality rates, respectively. we define diabetes by the presence of hyperglycemia, but we also know that, even among persons not known to have diabetes, the development of hyperglycemia in the setting of infection, trauma, surgery, or a cardiovascular event is associated with adverse outcome. it is then logical to ask whether the adverse outcome of covid- among persons with diabetes is related to the degree of hyperglycemia and, if so, whether this represents a causal relationship or rather shows that the severity of illness in a given individual with diabetes leads to both higher blood glucose concentration and greater likelihood of mortality. so far, reports from different data sets are somewhat contradictory. the same whole-population uk data set reported that, compared with those having glycated hemoglobin (hba c) - mmol/mol ( Á - Á %), covid- -related mortality with hba c of mmol/mol ( Á %) or more was . fold greater among persons with type diabetes, and among those with type diabetes, mortality with hba c - ( . %- . %), - ( . - . ), and ≥ ( . %) was increased . , . , and . -fold, respectively. a different uk data set of > million adult national health service patients gave an adjusted mortality hazard ratios of . and . among those with diabetes having hba c < . % and ≥ . %, respectively. specific hospitalized patient data sets, however, do not show that prior glycemic control, as reflected in hba c, are associated with different likelihood of adverse outcome among persons with diabetes. in an iranian hospital, persons with hba c . - had a similar mortality rate ( %) to that of persons ( %) with hba c %- . %. in analysis of persons with diabetes hospitalized for covid- in france, the outcome of tracheal intubation or death by day was not associated with hba c level on admission, although there was a linear correlation with admission plasma glucose, as well as with body mass index. another study, of persons with diabetes hospitalized for covid- in new york, showed no association of mortality with hba c on admission, whereas obesity, as well as increasing age and male sex and increasing complexity of outpatient diabetes treatment, were again associated with greater likelihood of adverse outcome. what can we conclude from the discrepancy between the population and hospital data sets? conceptually, several sets of mediators of adverse covid- outcome may exist among persons with diabetes (box ). there may be a direct risk associated with hyperglycemia. hyperglycemia may, however, be a marker of stress of illness. the risk seen among persons with diabetes may be because of insulin resistance, inflammation, hypercoagulation, or underlying obesity. and diabetes is associated with cardiovascular disease, chronic kidney disease, dyslipidemia, associations of type and type diabetes with covid- -related mortality in england: a whole-population study risk factors for covid- -related mortality in people with type and type diabetes in england: a population-based cohort study factors associated with covid- -related death using opensafely wellcontrolled vs poorly-controlled diabetes in patients with covid- : are there any differences in outcomes and imaging findings? phenotypic characteristics and prognosis of inpatients with covid- and diabetes: the coronado study preadmission diabetes-specific risk factors for mortality in hospitalized patients with diabetes and coronavirus disease national inpatient diabetes covid- response team. concise advice on inpatient diabetes (covid:diabetes): front door guidance. downloaded key: cord- -pgu crhs authors: golledge, jonathan; fernando, malindu; lazzarini, peter; najafi, bijan; g. armstrong, david title: the potential role of sensors, wearables and telehealth in the remote management of diabetes-related foot disease date: - - journal: sensors (basel) doi: . /s sha: doc_id: cord_uid: pgu crhs diabetes-related foot disease (dfd), which includes foot ulcers, infection and gangrene, is a leading cause of the global disability burden. about half of people who develop dfd experience a recurrence within one year. long-term medical management to reduce the risk of recurrence is therefore important to reduce the global dfd burden. this review describes research assessing the value of sensors, wearables and telehealth in preventing dfd. sensors and wearables have been developed to monitor foot temperature, plantar pressures, glucose, blood pressure and lipids. the monitoring of these risk factors along with telehealth consultations has promise as a method for remotely managing people who are at risk of dfd. this approach can potentially avoid or reduce the need for face-to-face consultations. home foot temperature monitoring, continuous glucose monitoring and telehealth consultations are the approaches for which the most highly developed and user-friendly technology has been developed. a number of clinical studies in people at risk of dfd have demonstrated benefits when using one of these remote monitoring methods. further development and evidence are needed for some of the other approaches, such as home plantar pressure and footwear adherence monitoring. as yet, no composite remote management program incorporating remote monitoring and the management of all the key risk factors for dfd has been developed and implemented. further research assessing the feasibility and value of combining these remote monitoring approaches as a holistic way of preventing dfd is needed. diabetes-related foot disease (dfd), including foot ulcers, infection and gangrene, is one of the leading causes of the global disability burden [ ] . about % of people who develop dfd hyperten sion outpatient blood pressure measuremen t cuff-less blood pressure monitor [ ] better implementation of anti-hypertensive medications and more frequent monitoring better informed management of blood pressure and reduced progression of macro and microvascular disease and mortality abnormal gait not routinely managed gait and activity monitor [ ] gait retraining and encouraging remote physical activity reduce gait abnormalities potentially reducing plantar pressures and ulcer incidence periphera l artery disease vascular laboratory assessment using ultrasound or doppler foot blood supply sensor [ ] earlier identification of complications and prompt medical management . the diagram outlines the key areas for prevention that can be targeted with sensors, wearables and telemedicine. table . examples of sensors and wearables with potential value for preventing dfd. pre-ulcerative lesions visits to podiatrist home foot temperature monitor and mobile phone applications [ , ] offloading of "hot spots" following confirmed persistent temperature differences reduced progression of at-risk sites prone to develop foot ulcers elevated plantar pressures offloading footwear plantar pressure monitor [ ] warning systems to stimulate offloading and better design and modification of footwear improved offloading with reduced ulcer development elevated plantar pressures and tissue stress patient education footwear adherence monitor [ ] behaviour change support counselling informed by objective data improved offloading adherence hyperglycaemia capillary glucose monitoring continuous glucose monitor [ ] intensive glycaemic control better informed management of hyper and hypoglycaemia and reduced progression of macro and microvascular disease hypertension outpatient blood pressure measurement cuff-less blood pressure monitor [ ] better implementation of anti-hypertensive medications and more frequent monitoring better informed management of blood pressure and reduced progression of macro and microvascular disease and mortality most foot ulcers develop due to repetitive trauma on the feet of people with a loss of protective sensation, such as those with diabetic peripheral neuropathy (dpn) [ ] . recurrent trauma results in local inflammation, or a "hot spot", which can be detected by an elevated temperature at the affected site [ ] . this offers a means to identify people who are likely to develop foot ulcers for immediate foot care, such as the removal of calluses and modifications of footwear, to achieve better offloading to reduce this repetitive trauma and in turn the hot spot [ ] . most previous studies have used infra-red thermometers to measure foot temperature at multiple sites on both feet and compare identical sites on opposite feet [ ] [ ] [ ] [ ] . prior research suggests that a temperature difference between identical sites on opposite feet of > . • c (equivalent to~ • f) on two consecutive days can accurately predict ulcer development [ , ] . it has recently been reported that the difference between the median of temperature at six key locations on one foot (the hallux, first, third and fifth metatarsal heads, the mid-foot and heel) and ambient temperature is also able to predict foot ulcer development with an excellent sensitivity, although with limited specificity [ ] . this potentially allows people with a unilateral foot ulcer and those with prior unilateral major amputation to also be monitored for the hot spots that are predictive of impending ulcers. given its predictive value, regular foot temperature monitoring offers the opportunity to instigate urgent offloading and foot care, such as callus removal, to prevent an impending foot ulcer. four randomised controlled trials have examined the efficacy of daily home foot temperature monitoring to signal the need for offloading in people at risk of diabetes-related foot ulcers [ ] [ ] [ ] [ ] . three of these trials [ ] [ ] [ ] , which were performed by the same team and included a total of participants, reported a significant and substantial reduction in foot ulcer incidence in those allocated to home foot temperature monitoring. the other trial [ ] , performed by a different research group and including only participants, reported no significant effect of home foot temperature monitoring and urgent offloading on foot ulcer incidence [ ] . a larger randomised trial involving participants is currently examining the cost-effectiveness and cost-utility of home foot temperature monitoring [ ] . recently, a further clinical trial reported on the efficacy of foot temperature monitoring performed at only monthly intervals at an out-patient clinic, rather than at home [ ] . a thermal camera was employed to identify "hot spots" in order to advise on interventions, such as reductions in physical activity and improved offloading of the concerned area [ ] . the trial included people with a past history of a diabetes-related foot ulcers and reported no benefit of the intervention in preventing foot ulcers or improving health-related quality of life [ ] . it is possible that these contrasting findings relate to the less-frequent monitoring of foot temperature performed, which may have missed an opportunity for the early identification of at-risk patients. these findings suggest the potential benefit of applying modern technology to regularly monitor foot temperature remotely in the participant's home in contrast to less frequent monitoring in outpatient clinics. the international working group on the diabetic foot (iwgdf) recently gave only a weak recommendation for the use of home foot temperature monitoring based on the moderate quality of evidence [ ] . this likely reflects the small size of prior trials, limitations in the design of the previous trials and the practical difficulties of implementing home foot temperature monitoring. the previous trials testing home foot temperature monitoring [ ] [ ] [ ] have excluded people with peripheral artery disease (pad), which is an established risk factor for foot ulceration, thereby limiting the generalizability [ ] [ ] [ ] . both pad and dpn have been reported to influence foot temperature [ ] . in a recent thermal imaging study, participants with pad had a significantly higher foot temperature than those that did not have pad [ , ] . in contrast, previous studies have reported a positive correlation between foot temperature and ankle brachial pressure index, implying that people with pad have a lower foot temperature [ ] . this disparity might relate to whether people with severe pad are studied or not. furthermore, prior clinical experience and recent reports of infrared thermography show that foot temperature rises immediately following successful revascularization in correlation with the increase in the ankle brachial pressure index [ ] . given the established effect of leg ischemia on foot temperature and the exclusion of participants with this problem from prior trials [ ] [ ] [ ] [ ] ] , the role of home foot temperature monitoring in people with pad remains unclear. the ongoing trial of home temperature monitoring detailed above only excludes people with critical limb ischemia (defined as a systolic ankle blood pressure < mmhg, systolic toe blood pressure < mmhg or transcutaneous oxygen pressure < mm hg) and therefore will better clarify the role of home temperature monitoring in people with milder forms of pad [ ] . accepting the need for additional evidence for home foot temperature monitoring in larger numbers of people at risk of dfd with broader inclusion criteria, there are also some practical challenges to implementing this preventative approach. previous trials have required participants to separately measure temperature at locations on their feet using an infrared thermometer daily [ , [ ] [ ] [ ] . importantly, all trials to date have used the same type of hand-held device, which has been found to be a time-consuming method and may not be feasible for the majority of people with diabetes, such as those that have impaired vision, impaired mobility or who have multiple comorbidities which all have impacts on self-care motivation. there is therefore interest in developing sensors to better automate home foot temperature monitoring to make this measurement much more user-friendly. the most advanced, currently described system for the automated measurement of foot temperature is the podimetrics mat [ , ] . this is a wireless mat that is designed to remotely monitor the temperature of the plantar surface of the foot with minimal involvement from the patient [ ] . if the mat is stepped on for a period of about s, it automatically takes a thermogram of both feet. the thermogram accurately measures temperature over the range of to • c and transmits the data securely to an approved server managed by the manufacturer. foot temperature asymmetry is automatically calculated based on the thermogram. in a prior study of participants with a past history of diabetes-related foot ulcers, a temperature difference of . • c between common sites on both feet correctly predicted % of foot ulcers, with an average lead time of days and a false-positive rate of % [ ] . increasing the temperature threshold to . • c decreased sensitivity to % but reduced the false-positive rate to %, with approximately the same lead time of days. about % of the participants used the system at least days a week. however, this device is not commercially available outside of the united states of america and may also be too expensive for individual use. other options for remotely monitoring foot temperature include a thermal camera incorporated into a mobile phone, insole devices or optical fiber based smart textiles, such as smart socks or insoles [ , , [ ] [ ] [ ] . smart phone infrared thermal imaging cameras have excellent agreement with more established infrared imaging systems and thus appear suitable for use in clinical practice [ ] . these devices may need more development to allow patients to use them easily at home, and the cost of such devices may be a potential limitation. smart socks have been tested in small numbers of people with dpn and been shown to be able to accurately and repeatedly measure temperature at multiple sites on both feet [ , ] . however, whether it is feasible to use these regularly over a prolonged follow-up process is not currently clear and remains to be investigated. a large randomised trial of participants with severe dpn is currently evaluating the effectiveness of daily home-based foot temperature measurements using an intelligent sensor-equipped insole combined with photo documentation in preventing foot ulcers [ ] . results from this trial will provide larger-scale evidence on the value of this approach. dpn leads to loss of intrinsic foot muscles and changes in foot shape [ ] . these changes can promote areas of high pressure within the plantar surface of the feet during standing or walking [ ] . a prior meta-analysis suggests that people with dpn and a history of foot ulcers have higher plantar pressures during walking than those with dpn who have not had an ulcer [ ] . the iwgdf guideline strongly recommended that people with a history of foot ulcers use footwear designed to reduce their high plantar pressures [ ] . plantar pressures are traditionally measured in clinical practice using highly designed pressure plates or insoles with pressure sensors located within health care or research facilities [ ] . systems such as the pedar ® (novel, munich, germany) and f-scan™ (tekscan inc, boston, ma, usa) are now available that can reproducibly measure plantar pressures within footwear [ ] . these systems have been used to confirm that therapeutic footwear is effective at reducing plantar pressures [ ] . they are also being extended to measure plantar pressures and other tissue stress on the plantar surface of the feet during everyday activity [ ] . patient access to such systems is limited, however, as they are only available in a small number of research or clinical settings, require specific protocols for obtaining data and are not available for home monitoring [ ] . these systems differ in relation to the types of sensors used to measure plantar pressure; for example, some have large capacitive sensors and others have smaller resistive sensors or piezoelectric sensors which are more temperature-sensitive. therefore, the user should be familiar with the advantages and disadvantages of each system, as this determines the application and the quality of data obtained [ , , ] . smart insoles, such as the surrosense rx system (orpyx medical technologies, calgary, alberta), have now been developed that can monitor plantar pressures and provide alerts directly to wearers [ ] . this system consists of a pressure-sensing insole that contains eight pressure sensors: three positioned under the metatarsal heads, two under the lateral plantar surface, one under the heel, one under the hallux and one under the lessor toes. the wearer receives an alert when sustained pressure is detected (pressure exceeding - mmhg and lasting over a -min period) and a pressure map of each foot showing the area where pressure is sustained [ ] . the alert thresholds are based on the integration of pressure data over time. the correct therapeutic response to the alert is the offloading of the area with sustained pressure within min of detection. in a study of people with a past history of foot ulcers, those receiving a great number of alerts (at least one alert every two hours) wore their offloading for longer and had better adherence in responding to alerts [ ] . most participants felt that the insoles were useful and achieved good performance [ ] . in a recent clinical trial [ ] , patients with dpn and a recent history of a plantar foot ulcers were studied. they were randomly assigned to either an intervention group that received audio-visual alerts via a smartwatch linked to the surrosense rx insole system and offloading instructions when aberrant pressures were detected or a control group that did not receive any alerts. this trial reported a % reduction in ulcer incidence in the intervention compared with the control group (incidence rate ratio . , % ci, . - . ; p = . ) [ ] . however, this trial had a small sample size and a large dropout of % during the wearing-in period of the insole system and a further % dropout in the intervention group during follow-up [ ] . in addition, the pressure feedback system used recorded pressure at a low sample frequency and failed to measure peak pressures. importantly, % of alerts were received during static weight bearing positions and only % during walking in the study [ ] . therefore, the usability and ease of implementing this type of device remains to be demonstrated in well-powered clinical trials. further evidence is needed for the widespread adoption of home plantar pressure monitoring. therapeutic footwear specifically designed to the shape of the patients' feet and targeted to reduce > % of peak plantar pressures is an established part of the management of people with dpn [ ] . such footwear is strongly recommended by the iwgdf guideline [ ] . however, prior randomised trials of offloading insoles or footwear have shown inconsistent results, with only four of the eight trials reporting a reduction in the incidence of foot ulcers [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . a likely contributor to the inconsistent results of these trials is the variation in adherence to offloading. in one of the trials, for example, it was reported that custom-made offloading footwear did not significantly reduce foot ulcer incidence [ ] ; however, among the participants that adhered to their custom-made offloading footwear for % of the time they were weight bearing, there was a significant reduction in the incidence of foot ulcers of % compared to the control group [ ] . this emphasizes the importance of adherence to wearing offloading footwear in order for it to be effective. in order to facilitate footwear use, accurate and objective data on adherence are needed. temperature sensors (thermistors) placed inside therapeutic footwear have been used to monitor offloading use [ ] . combining such sensors along with activity monitors allows footwear adherence as a proportion of daily weight-bearing activity to be estimated [ ] . a previous study showed that a temperature threshold of • c to indicate that footwear was worn had a sensitivity of %, a specificity of %, a negative predictive value of % and a positive predictive value of % in determining footwear use [ ] . past research also demonstrates that these temperature sensors are a valid method of estimating footwear adherence compared to adherence measured using a time-lapse camera [ ] . it is anticipated that small sensors will soon become available that can accurately monitor an individual's footwear use and activity and provide "live" data seamlessly to remotely located health practitioners [ ] . this objective footwear adherence data may be used to inform remotely delivered motivational interviewing aimed at increasing the frequency of offloading [ ] . further developments are needed before this approach can be implemented in a remote management program. it should be noted that there is a paucity of commercially available sensors for monitoring adherence easily and accurately, and most of the aforementioned sensors have only been used in a research context [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the optimal control of glucose, blood pressure and lipids is frequently not well implemented among people that develop dfd [ ] . people with dfd have an increased risk of all-cause mortality (relative risk (rr) . , % confidence intervals (ci) . , . ) and fatal myocardial infarction (rr . , % ci . , . ) compared to people with diabetes without dfd [ ] . in people with a history of diabetes-related foot ulcers, the risk of cardiovascular mortality is about % over years and the annual mortality rate is estimated to be about % [ ] . this emphasizes the importance of optimizing medical management in this population. glycaemic control is important for preventing both macro and microvascular complications, and a meta-analysis of past randomised trials suggests that intensive glycaemic control prevents amputations [ ] . in clinical practice, diabetes management is usually informed by self-monitoring of blood glucose [ ] . wearable or implantable sensors are now available for the continuous monitoring of glucose [ ] ; these use enzymatic technology to monitor interstitial fluid rather than blood glucose [ ] . these sensors can measure glucose up to every min non-invasively for a period of about one week, after which most devices need to be replaced [ ] . such sensors have been incorporated into closed loop systems which provide automated insulin delivery to people with type diabetes with improvements in glycaemic control [ ] . recent meta-analyses of randomised trials comparing self-monitoring and the continuous automated monitoring of glucose in people with type diabetes suggest that continuous monitoring facilitates better glycaemic control [ , [ ] [ ] [ ] . the use of such devices is now recommended by the north american guidelines for some patients, such as those with poor glycaemic control (hba c ≥ %) [ ] . a recent trial showed that flash glucose monitoring (measuring interstitial fluid glucose) can be implemented in the primary care environment, although it may not be superior to sensors , , of traditional methods as measured by hba c at months [ ] . the application of continuous glucose monitoring for people with diabetes who are at a high risk of complications such as dfd may have substantial benefits, but access to this technology is currently limited to selected patients due to the current high expense of such monitoring systems. high blood pressure is another important risk factor for complications in people with dfd. anti-hypertensive medications, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been shown to reduce the incidence of cardiovascular events in people at risk of dfd, such as those with pad [ ] . control of blood pressure is, however, frequently suboptimal in people at risk of dfd [ ] . in a recent study of people with pad, about % had a systolic blood pressure above the target level of mmhg [ ] . currently, blood pressure is monitored through the assessment of pulsation linked with an inflatable cuff placed around the upper arm. novel cuff-less wearable devices have now been developed for the estimation of blood pressure and may provide a more practical way of repeatedly monitoring blood pressure and facilitating better management [ , ] . these devices use varying methods, such as pulse transit time, laser doppler flowmetry and artery vibration, to calculate blood pressure. some of these devices are available commercially, such as from tmart technologies limited, china and somnomedics, germany, and some-but not all-have been shown to accurately measure blood pressure in small numbers of people with comparable results to classical cuff-dependent machines and also intra-arterial assessments [ ] [ ] [ ] . the accuracy and value of these devices in improving the medical management of people at risk of dfd need further evaluation. people at risk of dfd also require lipid control. the intensive lowering of low-density lipoprotein has proven efficacy in reducing major adverse cardiovascular and limb events in people at risk of dfd, such as those with pad and diabetes [ , ] . low-density lipoprotein sensors have also been built, although further development and testing is needed before they will be ready for widespread use [ ] . medication non-adherence is often defined as taking less than % of the prescribed treatment [ ] . due to a variety of factors including cost and regimen complexity, adherence to diabetes treatment is often poor and is reported to vary from % to % across differing populations [ , ] . in order to achieve optimal control of risk factors, it is important that patients adhere to prescribed medications. sensors have now been developed that are capable of monitoring medication ingestion; for example, proteus discover provides data on medication taking and physical activity to both patients and practitioners [ ] . it consists of an ingestible sensor, a wearable sensor patch, a patient mobile app and a provider web portal. after being swallowed, the ingestible sensor is activated and sends a signal with a specific code that is detected by the patch. when the ingestible sensor pill is taken with medication, it can measure medication ingestion adherence. the patch also can measure activity, heart rate and step count. data from the patch are transmitted to a mobile device to be viewed by the patient and then to the cloud and onto a web portal for a practitioner to view. the mobile device app prompts the patient to take their medication doses as scheduled. a previous study suggested that proteus discover can improve control of blood pressure, low-density lipoprotein and hba c [ ] . such sensors could have a role in people at risk of dfd, but this needs further testing and consultation with patients and other key stakeholders. there is a lack of head-to-head clinical trials comparing the various types of sensors or monitors available for remote medical management described above; more importantly, the control arms in clinical trials of remote monitoring systems have varied substantially. therefore, there is an ongoing need to assess the suitability of these sensors for optimizing medical management in people at risk of dfd. people with dpn often have an abnormal gait, which likely contributes to high plantar pressures and the risk of foot ulcers [ ] . the assessment of gait is complex, but wearables have now been developed that are capable of monitoring it remotely [ ] . such information can be potentially used for the design of a gait retraining program aimed at reducing plantar pressures and risk of ulceration. artificial intelligence systems, such as the gait-enhancing mechatronic system (gems) (samsung, seoul, korea), have also been developed to improve gait and redistribute foot pressure, although their exact role in health care is not currently clear [ ] . other web-based and remotely delivered methods of physical therapy and rehabilitation may provide further ways to improve gait in people with dpn [ ] . a clinical trial is currently in progress to test whether a remotely delivered physical therapy program can improve dpn symptoms and severity as well as gait and function [ ] . artificial intelligence has also been applied to the development of a robotic systems for assessing dpn that are potentially able to screen people for their risk of developing dfd [ ] . there is a current cochrane review that is reviewing the evidence of the accuracy of all potential simple tests for screening dpn to supply more comprehensive evidence [ ] . there is also interest in the development of sensors to determine foot perfusion [ ] ; the vascular early warning system (vews), for example, functions by using infrared optical sensors placed on the toe and dorsum of the foot to measure changes in blood volume within the microvasculature during foot elevation [ ] . these sensors have not been tested in well-powered randomissed clinical trials or in comparison to standard care [ ] . one challenge with assessing these systems in clinical contexts is that standard care can vary substantially between health services, countries and continents; therefore, the role of such systems in delivering preventative medicine remains unanswered but is an exciting future area of research. it is possible that remotely delivered gait rehabilitation programs may reduce the risk of dfd. for people with dfd, treatment and education typically occur in an outpatient clinic weekly or bi-weekly. although remote monitoring methods for people with dfd using smartphone applications have been developed, these are still in their infancy and have not been widely tested or implemented [ ] [ ] [ ] . despite their potential application in remote dfd monitoring, the diagnostic accuracy of mobile phone images is reported to be poor and therefore should not be used as a stand-alone diagnostic instrument for dfd [ ] . this is a rapidly evolving area; therefore, novel mobile phone applications and remote monitoring methods may improve over time. telehealth is an established means of performing medical consultations [ ] . the benefit of using telehealth for managing foot ulcers has been demonstrated in several meta-analyses and systematic reviews [ ] [ ] [ ] . most of the evidence comes from two clinical trials [ , ]: the first trial evaluated the effectiveness of a telehealth intervention made up of : online:standard outpatient consultations compared to a usual care intervention consisting of three standard outpatient clinic visits on ulcer healing in people [ ] . the authors reported no significant difference in ulcer healing or amputation between the two methods but did show an increased risk of mortality in the remote monitoring group (hr = . , % ci: . - . ). this was a surprising finding that was not explained by any of the studied covariates [ ] . a more recent cluster randomised controlled non-inferiority trial of adults evaluated telehealth [ ] . weekly telemedicine consultations via an interactive web-based ulcer record and a mobile phone for communication with the healthcare specialist in addition to outpatient clinic visits every weeks was compared to visiting the outpatient clinic every second week [ ] . the trial showed no difference in time to ulcer healing and a superiority in prevention against amputation (mean difference: . %, % ci: . %, − . %) in the intervention group [ ] . an important factor to note in these trials was that the intervention arms all included some face-to-face consultations with a health care professional. based on anecdotal evidence, at present, there appears to be a range of different approaches to telemedicine that are used globally, ranging from mobile phone-based consultations, hospital-based remote management consultations and the phone-based review of patients. however, how such approaches should be designed in line with face-to face care has not been well defined in the literature. there has been limited study of the value of telehealth consultations in preventing rather than treating dfd. the covid- pandemic has provided a stimulus for studies testing the use of remote monitoring technologies and telehealth consultations in preventing dfd [ , ] (see table ). table . currently available and required evidence for the remote assessment and prevention of diabetes-related foot disease. home foot temperature monitor a number of small rcts show a decreased incidence of foot ulcers in people performing home-based temperature monitoring lack of a widely tested and user-friendly way of identifying "hot spots" generalizability from prior smaller studies in select populations [ , ] plantar pressure monitor possible to monitor plantar pressure remotely and use patient alarms to warn patients of impending sites of tissue breakdown as reported in one small rct unclear if technology can be further developed to be more user-friendly and whether the findings are applicable and would be effective on a widespread basis [ ] footwear adherence monitor technology has been developed to accurately measure footwear adherence need for widespread testing of value of using devices patients' views on use of adherence monitoring is still unclear [ ] continuous glucose monitor highly developed area of monitoring and tested in multiple rcts with proven benefit in improving glycaemic control (hba c) whether this remote monitoring improves outcomes in people at risk of developing dfd remains unclear [ ] cuff-less blood pressure monitor technology developed to assess this reported to be accurate in a small number of studies currently unclear whether these devices can be used on a widespread scale [ ] foot blood supply and sensation assessment technology still in the early developmental stages for monitoring the benefit of these devices in improving clinical outcomes need to be further evaluated in rcts [ , ] legend: pad = peripheral artery disease, rct = randomised controlled trial, hba c = glycated haemoglobin a c, dfd = diabetes-related foot disease. sensors, wearables and telehealth approaches capable of remotely monitoring the key risk factors for dfd have 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reliability of remote diabetic foot ulcer assessment using mobile phone images telemedicine technology and clinical applications telehealth and telemedicine applications for the diabetic foot: a systematic review role of telehealth in diabetic foot ulcer management-a systematic review telemedicine in diabetic foot care: a systematic literature review of interventions and meta-analysis of controlled trials key: cord- - h w eq authors: schiaffini, riccardo; barbetti, fabrizio; rapini, novella; inzaghi, elena; deodati, annalisa; patera, ippolita p; matteoli, maria c; ciampalini, paolo; carducci, chiara; lorubbio, antonella; schiaffini, gabriele; cianfarani, stefano title: school and pre-school children with type diabetes during covid- quarantine: the synergic effect of parental care and technology date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: h w eq abstract introduction management of type diabetes (t d) poses numerous challenges, especially for young children and their families. parental care positively influencesthe outcomesofchildren with t d, while there are often criticisms in school environment. the covid- pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. aim of the study to evaluate the effectiveness of exclusive return to parental care in pre-school and school children with t d treated with tandem basal iq system during the covid- pandemic. patients and methods children (m:f = : ) with t d have been evaluated. we compared insulin and cgm data (tir, tbr and tar) of two periods: pre-cov and in-cov, in which children have transitioned from normal school attendance to the exclusive care of their parents. results during the in-cov period a significantly (p < . ) higher median value of tir ( , %) was observed as compared to pre-cov period ( , %). patients also showed a statistically significant difference (p < . ) between the in-cov period and the pre-cov period as concerning the tar metric: respectively , ± , % vs , ± , %. the difference between the bolus insulin doses was statistically significant (pre-cov , iu/day, in-cov , iu/day – p< . ). conclusion our observational real-life study confirms the positive effect of parental care in t d very young children and demonstrates that during the covid- pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle. type diabetes (t d) is one of the most common chronic diseases in infancy   and the most frequent endocrinopathy in childhood. it is estimated that about children are affected by t d in italy  . correct management of t d involves frequent blood glucose monitoring, insulin therapy, dietary indications and structured physical activity, representing a high burden on young children and their families. because of these daily challenges, effective diabetes treatment requires -in principlecomplete parental dedication and involvement  . moreover, parents and teachers of kindergarteners and of children in primary school usually experience the additional challenges of a critical management in school hours, due in particular to the fear of hypoglycemia, the extreme glycemic variability of this age group and the difficulties in correcting the hyperglycemic peaks. parents of kids diagnosed with t d early in life tend to be proactive in the care of diabetes of their children during school and pre-school periods with a strong parental involvement in disease management and a positive influence on the metabolic and psychosocial outcomes  - . conversely, parents of patients diagnosed in late childhood or in adolescence are less involved in care, and usually this is associated with less than optimal glycemic control  . nevertheless, parental care remains important throughout childhood into young adulthood and a progressive sharing of responsibilities is considered an important step towards a therapeutic approach well balanced between self-monitoring and quality of life  . the gap between family and school care capacities can be bridged by the use of technologies in the treatment of diabetes in children. in the last two decades, new tools for the management of children with t d have been proven to be safe and useful. continuous subcutaneous insulin infusion (csii), continuous glucose monitoring (cgm) and remote monitoring in case of multiple daily injections (mdi) seem to be valid options to manage children with diabetes. in particular, cgm systems and remote control access have improved the treatment and management of diabetes during school hours. parents of kindergartner (pre-school) and school children reported that the use of remote monitoring and cgm was effective in control glucose excursions  . in particular, the use of technologies capable of reducing hypoglycemic risk, such as the tandem basal iq system, have proven to be helpful in reducing parental burden. this system is able to prevent/reduce hypoglycemia thanks to cgm real-time data and was introduced in italy about months ago. covid- pandemic has forced children and parents to spend many hours together at home, reducing structured physical activity while bringing back diabetes care in the hands of parents. we aimed at investigating whether this unusual situation lead to an improvement or a worsening of the glucose control. this is a real-life, retrospective, observational study aimed at evaluating how constant parental care compared to spending time outside home affected glycemic control in pre-school and school children with t d utilizing tandem basal iq system before and during the quarantine period due to pandemic covid- infection. the diabetes unit of the bambino gesù children's hospital -rome, italy, regularly follows type diabetes pediatric patients (age - years); of these patients, use the tandem basal iq technology (considered as an inclusion criteria) and are in the school-preschool age range; finally pre-school and school children (m:f = : ) with t d have been retrospectively evaluated ( patients/parents resulted not reachable during the lockdown period). the mean age was , ± , years (range , - , years) and the diabetes duration was at least of year. enrolled patients were all being intensively insulin treated with the tandem basal iq technology for at least six months. tandem basal iq technology consists of an insulin pump integrated with a dexcom g glucose sensor capable of previously suspending insulin delivery in case of hypoglycemia prediction. a multidisciplinary team (diabetologist, nurse, dietitian and psychologist) dispensed a standardized protocol of education to all patients enrolled and their parents at the time of diabetes diagnosis and at months intervals. all the patients and their families were educated in carbo-counting procedures and were instructed to follow a balanced nutritional program consisting in % of carbohydrates, % of proteins and % of lipids. the study was conducted according to the declaration of helsinki. participants and their parents provided informed consent to have their cgm data downloaded at regular intervals, as part of routine clinical control and the study was ethically approved. potential conflict of interest do not exist. beginning march , , the start of the lockdown in italy, all patients and families were asked to stay at home due to the covid- pandemic emergency. during the pandemic, the children maintained the same diet with a similar distribution between the different macronutrients and they were unable to carry out any structured physical activity, as often happens also in routine life, considering the young age of the group. we compared cgm data of the last two weeks of "normal life" (normal school attendance) (pre-cov period) with the first two weeks of confinement at home (in-cov period) . the following cgm metrics were evaluated: time in range (tir -percent of time in the ideal range of glucose between and mg/dl), time above range (tar -percent of time above mg/dl), time below range (tbr -percent of time below mg/dl). we also compared the insulin requirement in the different periods, in terms of total insulin (iu/day), basal insulin delivery and insulin administered as boluses. all data were extracted from the dexcom clarity and diasend platforms. results are reported as the mean ± sd. normal distribution was assessed by shapiro-wilk test. mean variations of distributions were evaluated using the student's t test for paired data. the entire analyses were performed using spss . (spss inc., chicago, ill, united states) with p < . considered significant. data from children (mean age , ± , years) (m:f : ) with t d and disease duration longer than year were analyzed. the percentage of time of cgm wearing was %. no significant differences between the two evaluated periods (in-cov vs pre-cov) were found in tbr (hypoglycemia): respectively , ± , % vs , ± , % (tab. ). in contrast, during the in-cov period a significantly (p < . ) higher median value of tir ( , %) was observed as compared to pre-cov period ( , %) (tab and fig. ). conversely, patients showed a lower tar during in-cov period than pre-cov period , ± , % vs , ± , %, p < . ). interestingly, no differences between in-cov and pre-cov periods were observed regarding the total insulin dose ( , vs , iu/day) and the basal insulin delivery ( , vs , iu/day), while a statistically significant difference (p< . ) was found between the mean bolus doses ( , vs , iu/day) and the daily number of correction boluses ( , vs , iu/day). in this group of pre-school and school t d children using cgm and semi-automated insulin delivery systems (tandem basal iq), the forced and exclusive return to parental care due to the "stay at home" rule decided by the italian government was associated with a better metabolic performance with higher percentage values of tir and lower mean values of tar. this result seems to be due to a greater use of correction boluses; in fact, our evaluation shows a significant increase in insulin boluses during the in-cov period as compared to pre-cov one. we speculate that similar results will be hardly seen in adolescents and middle school teens, because the management of the disease in these age groups remains in the hands of the patients even during confinement the and physical activity has no significant impact in younger children. nonetheless, we think that it would be worthwhile to investigate older age groups in countries where the lockdown is still in force, though we recognize that other variables -say good or bad interaction with parents-are probably at work in adolescents with t d. we predict that a better outcome in terms of tbr could be likely in this group because of increased regularity of meals' content and stringent control on alcohol consumption  . the study has some limitations: first, patients selection limited only to preschool/school children who used tandem basal iq technology can represent a selection bias; secondly, the small size of the sample may not make the results obtained generalizable. our observational real-life study confirms the positive effect of parental care in t d very young children and that, though new technologies can potentially improve diabetes outcomes also in this sub-population, maintenance of a good glucose control remains largely dependent on family competence and education  . usually the majority of young people with t d spend many hours at school. trained school-staff is therefore essential to provide a safe environment for children with diabetes. teachers, along with the school's auxiliary staff, play a key role in reducing strong glycemic oscillations typical of younger children  . our study shows also a no significant differences in tbr, despite the shift to predominant parental care. this can be explained by the fact that all the evaluated children were already using a technology (tandem basal iq system) that effectively reduces the risk of hypoglycemia and therefore for this specific metric it can be assumed that parental intervention does not change the outcomes. in the past decades, technological innovations have revolutionized the treatment of t d and the real-world data highlighted that patients using insulin pump therapy have a better short and long-term glycemic control relative to the matched injection therapy groups  . however, despite the use of technology, parental intervention still seems to be more effective and probably the difference in the near future could be made by the spread of hybrid closed loop (hcl) systems. in the real-world experiences hcl use is associated with improved glycemic control and no change in psychosocial outcomes  . why children with t d attending school are often not adequately managed? recent studies showed that a limited availability of glucagon kits, the shortage of trained personnel able to manage daily diabetes-specific emergencies and a reduced ability to perform an adequate carbohydrate counting, considered an effective means to provide good glycemic control, are the main causes  - . consequently, family-based interventions for youth with t d are believed to be effective at improving diabetes outcomes  . since young patients with t d spend most of daytime at school, teachers and assisting personnel should receive appropriate training in order to provide a safe environment. however, it is likely that teachers of kindergartens, preschools and primary schools have not enough knowledge to appropriately assist children with t d  - . this may negatively reverberate on trust in school personnel of parents of very young children with t d, whose perception of the burden of care is very strong. thus, health care providers, parents, teachers, and school assistants of youngsters with t d should team up to improve, by specific educational programs  - , the skills to handle the disease and guarantee a safe attendance at school. type diabetes evaluating parents' self-efficacy for diabetes management in pediatric type diabetes collaborative involvement of primary and secondary caregivers: associations with youths' diabetes outcomes the impact of managing school-aged children's diabetes: the role of child behavior problems and parental discipline strategies caregiving for children with type diabetes and clinical outcomes in central india: the idream study shared responsibility for type diabetes care is associated with glycemic variability and risk of glycemic excursions in youth use of remote monitoring with continuous glucose monitoring in young children with type diabetes: the parents' perspective social consumption of alcohol in adolescents with type diabetes is associated with increased glucose lability, but not hypoglycaemia the impact of technology on current diabetes management diabetes care in the school setting: a position statement of the american diabetes association real-world outcomes of insulin pump compared to injection therapy in a population-based sample of children with type diabetes six months of hybrid closed loop in the real-world: an evaluation of children and young adults using the g system are children and adolescents with type diabetes in saudi arabia safe at school? effects of carbohydrate counting method on metabolic control in children with type diabetes mellitus family-based interventions targeting improvements in health and family outcomes of children and adolescents with type diabetes: a systematic review level of knowledge and evaluation of perceptions regarding pediatric diabetes among greek teachers special needs of children with type diabetes at primary school: perceptions from parents, children, and teachers i'm essentially his pancreas": parent perceptions of diabetes burden and opportunities to reduce burden in the care of children < years old with type diabetes ispad clinical practice consensus guidelines : management and support of children and adolescents with type diabetes in school the authors declare no conflict of interest. the authors received no funding from an external source. key: cord- - ti l ea authors: gupta, ritesh; hussain, akhtar; misra, anoop title: diabetes and covid- : evidence, current status and unanswered research questions date: - - journal: eur j clin nutr doi: . /s - - - sha: doc_id: cord_uid: ti l ea patients with diabetes who get coronavirus disease (covid- ) are at risk of a severe disease course and mortality. several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. however, there are many contentious issues about which the evidence is rather limited. there are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. similarly, despite the recognition of angiotensin converting enzyme (ace ) as the receptor for severe acute respiratory syndrome coronavirus (sars cov- ), and the role of ace in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ace) inhibitors and angiotensin receptor blockers (arb) in these patients. management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. there is a need to further study the natural course of covid- in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course. the high prevalence of diabetes globally makes it a frequent comorbidity in patients with coronavirus-associated disease . though diabetes increases the risk of infection in general, most studies have reported prevalence of diabetes almost similar to that in general population in patients with covid- . a meta-analysis of eight trials in china showed that diabetes was present in % of , patients with covid- [ ] . understandably, prevalence of diabetes in patients with covid- varies by region, age and ethnicity. it is not known whether patients with diabetes with well-controlled blood glucose levels have an increased risk of infection with severe acute respiratory syndrome coronavirus (sars cov- ). patients with diabetes who develop covid- have been seen to have a worse prognosis and increased mortality in most studies. in chinese patients with diabetes a hazard ratio of . ( % ci, . - . ; p = . ) for acute respiratory distress syndrome (ards) [ ] has been reported. further, meta-analysis of nine studies from china (n = ) showed a significant correlation between severity of covid- and diabetes (or, . , % ci; . - . ; p < . ) [ ] . similarly, case fatality rate was . % in patients with diabetes as opposed to . % in those without diabetes in a report of , patients of covid- by chinese centre for disease control [ ] . a recent study in patients with covid- in centres across the usa found diabetes to be associated with more than fourfold increase in mortality [ ] . how diabetes increases severity of covid- is unclear, though several factors may be responsible (table ) . poor glycaemic control impairs several aspects of the innate and adaptive immune response to viral infections and to the potential secondary bacterial infection in the lungs [ , ] . defects in immunity namely inappropriate t-cell action, impaired natural killer cell activity and defects in complement action could reduce viral clearance [ ] . interestingly, ards in patients with covid- is driven by severe hypoxaemia despite relatively well-preserved lung mechanics. pre-existing proinflammatory state could accentuate the cytokine storm, which is believed to be responsible for ards as well as multi-organ dysfunction in covid- [ ] . in this context, it is important to note that there is strong association between type diabetes, obesity and abnormal secretion of adipokines and cytokines like tnf-alfa and interferon, which may further impair immunity and predispose to severe infection [ ] . further, diabetes is associated with increased plasminogen levels which has been postulated to increase the virulence of sars cov- [ ] . presence of these inflammation and prothrombotic factors has been shown in a study in patients hospitalised with covid- in wuhan, china; significantly higher serum levels of interleukein , erythrocyte sedimentation rate, creactive protein, ferritin, fibrinogen and d-dimer were reported in patients with diabetes compared with those without diabetes [ ] . increased viral replication in diabetes may also due to an increase in furin, which is a type- membranebound protease involved in the entry of coronaviruses into the cell [ ] . in addition, pre-existing comorbidities associated with diabetes like hypertension, coronary artery disease and chronic kidney disease further worsen the prognosis. lastly, hypoglycaemia which could occur during treatment of diabetes may additionally worsen the clinical outcomes. in this respect role of angiotensin converting enzyme (ace ) receptor in pathogenesis of covid- in patients with diabetes is intriguing. sars cov- enters the cell by binding to ace , a process which involves many steps and several enzymes and proteins [ ] . there is experimental evidence for downregulation of ace in diabetes [ ] , which may predispose to more severe lung injury. on the other hand, ace is a receptor for sars cov- and this downregulation might reduce the entry of virus into cells. these issues are further discussed below in context of use of anti-hyperglycemic and anti-hypertensive drugs. the precise effect of treatment with various oral antihyperglycaemic agents on the severity of covid- is not known, though there are some theoretical considerations. metformin has shown modest benefits in lower respiratory tract infections and pulmonary tuberculosis [ ] , though gastrointestinal tolerability in sick patients is of concern. thiazolidinediones have been shown to increase ace levels [ ] . however, propensity of thiazolidinediones to cause fluid retention and the risk of congestive heart failure in covid- would make these agents unfavourable for treatment. glucagon-like peptide- agonists have has been shown to increase ace and increase surfactant in experimental animals [ ] . practical significance of changes in ace levels with use of thiazolidinediones and glucagon-like peptide- agonists is not known. sulfonylureas are effective, but the risk of hypoglycaemia especially in the setting of irregular meals might preclude their use. nevertheless, sulfonylureas can be considered whenever blood glucose monitoring is possible. there is some data regarding use of dipeptidyl peptidase (dpp ) inhibitors from previous viral epidemics. dpp is the prime receptor for middle east respiratory syndrome coronavirus responsible for its entry into cell [ ] . hence the possibility of dpp facilitating the entry of sars cov- into the cell cannot be ruled out. in that context, it is an interesting postulation that widespread use of dpp inhibitors in india and many other countries might be protecting individuals with diabetes from this infection. on the other hand, dpp inhibitors can potentially interfere with immune response which may be harmful, but clinical data from dpp inhibitors has shown that this is generally not the case [ ] . there is increasing use of sodium glucose cotransporter (sglt- ) inhibitors worldwide and in india. interestingly, sglt- inhibitors could also activate ace indirectly especially if used along with ace inhibitors [ ] . there is a hypothetical possibility of sglt- inhibitors reducing lactate production because of reduction in oxygen demand of tissues, which could reduce viral entry by raising cytosolic ph [ ] . further, caution about dehydration and the possibility of euglycaemic ketoacidosis need to be observed when using sglt- inhibitors in sick patients with covid- . insulin has also been shown to increase ace expression by attenuating the effect of a disintegrin and metalloprotease (adam- ) [ ] . practical relevance of these findings is not known at present. in any case, insulin thus, it appears safe to continue the usual antihyperglycemic medications in most patients who have mild infection, good general condition and normal oral intake. however, sglt- inhibitors might need discontinuation due to the risk of dehydration and euglycaemic ketoacidosis. metformin may also need to be stopped if there is vomiting or poor oral intake. doses of other antihyperglyacemic drugs like sulfonylureas and insulin may have to be altered depending upon the blood glucose levels. hospitalised patients especially those requiring intensive care would need insulin for glycaemic control. angiotensin converting enzyme (ace) inhibitors/ angiotensin receptor blockers (arb) these are commonly used drugs in patients with diabetes, especially in those with hypertension and kidney dysfunction. there have been a lot of literature and debate whether these drugs could benefit or harm patients having covid- infection. this issue is discussed below. scientific experimental data that support potential harm duet to ace inhibitors/arb in covid- there has been a lot of interest in ace inhibitors and arbs following the identification of ace as the receptor for sars cov- . ace inhibitors and arbs increase the levels of ace by inhibiting the conversion of angiotensin to angiotensin . increased ace expression could theoretically increase viral binding and entry into cell, though there is no clinical evidence to support this otherwise attractive hypothesis. reduced angiotensin as a result of ace inhibition and increased angiotensin - as a result of increased activity of ace could reduce the cytosolic ph, which could result in more favourable environment for viral endocytosis [ ] . also, angiotensin - has been shown to increase sympathetic activity by acting on mas receptors in the brainstem, which could contribute to cardiovascular morbidity observed in these patients [ ] . however, most of these concerns are hypothetical with minimal evidence. scientific experimental data that support benefit due to ace inhibitors/arb in covid- increased ace might not result in increased viral entry because of the limited availability of the serine protease tmprss , which is required for viral binding [ ] . increased ace and consequently angiotensin - have vasodilatory and antifibrotic effects and have been shown to be protective against lung injury in animals [ ] . treatment with arbs was reported to reduce mortality in ebola virus infection [ ] . previously, a small study in ten patients with ards showed that recombinant ace was well tolerated and led to an increase in angiotensin ( - ) levels [ ] . ( ) there are no controlled studies on the use of ace inhibitors and arbs in patients with covid- . ( ) the clinical evidence is inconclusive. while one study in china did not find any association of ace inhibitor use with severity of disease, there was an increased mortality in patients with covid- receiving ace inhibitors and arbs in another study [ , ] . one study in the usa did not find any significant difference in mortality in patients who received ace inhibitors and arbs and those who did not [ ] . in this subject situation is far from clear and there are too many unknown factors, which might be operative in the interaction between ace , diabetes, ace inhibitors/arbs and lung injury. the lack of evidence for either benefit or harm has prompted european society of cardiology council on hypertension, european society of hypertension and american heart association to advise continuing with ace inhibitors and arbs in case a patient develops covid- [ ] . a clinical trial is underway to study the arb losartan and recombinant human ace in patients with covid- . there have been several commentaries on the relationship between diabetes and covid- [ ] . however, several unanswered questions remain, about which the knowledge and information is limited. clearly, further research could lead to important insights ( table ) . some of these are discussed below. ( ) what is the natural history of covid- in patients with diabetes? the natural course of the disease after infection of patients with diabetes with sars cov- has not been documented well. for example, we don't know if the incubation period is different in people with diabetes. it is also possible those patients of diabetes who are young, have short duration of diabetes, and well controlled may have less severe covid- infection. there is a possibility of reduced viral clearance in diabetes as has been reported in patients who are on corticosteroids [ ] . this could have public health implications as the patients with diabetes could remain infectious for a longer period than those without diabetes. a. chloroquine has also been licensed for use in india for patients with type diabetes. although the efficacy of chloroquine is not proven; it has been used in patients with covid- [ ] . chloroquine has a weak anti-hyperglycaemic effect and there is a theoretical risk of hypoglycaemia when used in combination with other antihyperglycaemic drugs. b. corticosteroids, though neither effective nor recommended, are frequently used in ards and sepsis and would worsen glycemic levels. ( ) covid- and pancreatic beta cells: there is significant expression of ace receptors in pancreatic islets and hyperglycaemia lasting up to years has been reported in patients with sars [ ] . direct injury to beta cells is a possibility and patients recovering from covid- might need major changes in anti-hyperglycaemic regimen. recently, new-onset diabetes has been reported in patients with covid- [ ] . ( ) suboptimal lifestyle measures and other issues during lockdown: a. there are restrictions on movement of people and 'lockdowns' in several parts of the world in order to contain the pandemic. this poses some challenges in the evaluation and treatment of patients with diabetes. there are limited opportunities for exercise as regular walks and visits to gyms or swimming pools are not possible. dietary irregularity could occur because of staying at home. b. there is considerable mental stress because of the unpredictability of the disease as well as social immobility as brought out in an excellent study in healthy people in china at the time when there was a huge burden of covid- there [ ] . c. patients may find it difficult to procure healthy foods, medicines, insulin, needles and glucose strips etc. because of partial or complete lockdowns. the problem becomes more pronounced with elderly, poor and disadvantaged sections of society. d. there could be underreporting of symptoms because of the perceived need to avoid visiting hospitals. all these factors could cause glucose dysregulation and could predispose patients to complications like infections, hyperosmolar coma, ketoacidosis and even acute cardiac events. a prediction model of the effect of lockdown in india on blood glucose showed a . % increase in hba c at the end of days of lockdown and future increase in diabetes-related complications [ ] . ( ) are people with well-controlled diabetes at higher risk of getting covid- infection than non-diabetic individuals? ( ) is there any effect of obesity on the severity of covid- in people with diabetes? ( ) is there any specific diet or supplement which could help patients of diabetes and covid- ? ( ) what is the role of renin angiotensin aldosterone system (raas) and inhibitors of raas in determining the predisposition to covid- and its severity? ( ) use of remote education and advice: telemedicine (also emails, texts) can be very helpful in these times to impart education and has been shown to improve glycaemia. telemedicine guidelines for physicians in india have been published [ ] . patients need to be educated about the need to visit the hospital urgently in emergency situations like vomiting, drowsiness, shortness of breath, chest pain, weakness of limbs, altered sensorium, etc [ ] . ( ) covid- testing for all patients with diabetes? given the increased severity of covid- in patients with diabetes, a case could be made for testing of all people with diabetes for the presence of disease. that would be a humongous task considering the high prevalence of diabetes. high-risk groups like those with high hba c, those with comorbidities, long duration of diabetes or elderly could be chosen for testing, however, utility of this approach remains to be proven, there are frequent false negative tests and repeated testing may be required in asymptomatic individuals. since there is no treatment currently recommended for asymptomatic people, therefore apart from isolating them, detecting these patients might not prove meaningful clinically. ( ) ethnic variations in severity of covi in patients with diabetes? in the united states, the disease has caused disproportionately more fatalities in blacks and asians compared with whites [ ] . south asia, africa and korea have seen much lower mortality than rest of the world. whether it is because of the different approaches topublic health measures, innate immunity or due to some ethnicity-specific variability in response to viral infection, or availability of good medical resources, remains to be studied. interactions between ethnicity, diabetes and severity of covid- will be of interest, considering the racial disparities in the prevalence of diabetes. according to a recent report, prevalence of covid- and mortality due to the disease correlated significantly with frequency of d allele in ace gene [ ] . such polymorphisms in ace gene as well as several other genes involved in the pathophysiology of covid- might be responsible for individual and ethnic variations in disease course. ( ) benefits of lockdown? there could be some positive effects of the social restrictions. a. patients have more time for self-care and could pay more attention to diet and exercise if motivated. b. some people have stopped or reduced alcohol and smoking because of non-availability. c. there has been significant fall in air pollution as a result of reduced industrial and vehicular emissions [ ] . increase in blood glucose has been reported with short-term rise in pm (particulate matter < microns in diameter) and glycaemic improvement could occur with the fall in pollution [ ] . in view of the issues highlighted above, it is important to recognise the importance of diabetes as a vital comorbidity in patients with covid- . there are several contentious issues and the ongoing research will hopefully shed more light on the behaviour of covid- in patients with diabetes. author contributions rg and am planned the outline of manuscript. rg reviewed the literature and wrote the manuscript. rg, 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coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetesrelated complications: a simulation model using multivariate regression analysis telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians clinical considerations for patients with diabetes in times of covid- epidemic the color of coronavirus, covid- deaths by race and ethnicity in the the host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in covid- infections covid- as a factor influencing air pollution? ambientair pollution and diabetes: a systematic review and meta-analysis key: cord- -y q cjbk authors: vallis, michael; tang, tricia; klein, gerri title: mental health in diabetes: never a better time date: - - journal: can j diabetes doi: . /j.jcjd. . . sha: doc_id: cord_uid: y q cjbk nan mental health in diabetes: never a better time we present this special issue of the canadian journal of diabetes at a very unusual time in all of our lives. not only has the covid- pandemic had an impact on populations worldwide, the mortality and health-related consequences of this disease have been magnified in some communities over others, specifically for individuals with diabetes. clearly, we are living through a global crisis that not only affects our health and mental health, but also has disrupted the economy, education and employment. as difficult as it is for us all, living with diabetes during this time of uncertainly caused by the covid- pandemic heightens the already daunting task of diabetes self-management. routines are disrupted, finances may be challenged and in this era of self-isolation, social supports are not as available. as diabetes care providers, the more we can help patients cope with the mental health impact of the pandemic, the better equipped they will be to perform all the behaviours necessary to keep their blood glucose levels in target. it is in this context that we offer this special issue on mental health and diabetes. planning this special issue started prior to the pandemic and was based on the beliefs that diabetes has an impact on the mental health of the person living with the condition, and that mental health affects a person's ability to perform diabetes-related selfcare. as stress increases, self-care decreases. so, we have organized this issue to highlight this bidirectional relationship. in providing diabetes care on a day-to-day basis, we see the effect diabetes exerts on emotional health. patients do not have the luxury of taking a break from diabetes. not a day goes by without having to be reminded of this demanding condition that requires constant, ongoing self-care decisions. ironically, the more invested in diabetes self-management our patients are (which is our explicit goal), the larger the psychological impact it will have. yared et al ( ) present a paper describing how a multidisciplinary type clinic has incorporated the assessment and management of diabetes distress into their practice. hendrieckx et al ( ) performed an audit in australia examining how persons with diabetes want to connect to their diabetes providers to address diabetes distress. lafontaine ( ) examines spousal support and relationship happiness in those with type diabetes. morgan et al ( ) offer a paper on selfcompassion, adaptive reactions and health behaviours that adds to our understanding of living well with diabetes. morrissey et al ( ) present a paper on the role of diabetes distress in adolescents and young adults living with type diabetes. demolitor et al ( ) present a public health perspective on the concept of diabetes distress. additionally, there are contributions examining the potential for negative mental health impacts in the form of bereavement and grief reactions in those with type diabetes (fraser [ ] ) and an important perspective paper on self-injury and suicide in those with diabetes (barnard-kelly et al [ ] ). with regard to psychological stressors in economically disadvantaged populations, kalra et al ( ) report on a scoping review of the rates of depression and diabetes distress in south asians from low-and moderate-income countries. this issue also offers a number of papers on mental health issues as they relate to diabetes. cimo et al ( ) present the outcomes of a diabetes education intervention in those living with diabetes and mental health disorders. wong and mehta ( ) examine the efficacy integration of psychiatric care into diabetes education clinics for patients with comorbidities of depression and diabetes. stenov et al ( ) offer the diabetes support needs of those living with serious mental health disorders. alessi et al ( ) examine alcohol use and clinical outcomes in youth and adults with type diabetes, and mehta and hirji ( ) review the outcome of structured education for patients living with type diabetes and substance abuse. benson et al ( ) examine depression in girls with type diabetes, obesity and polycystic ovary syndrome. finally, riggin explores the relationship between gestational diabetes and perinatal mental health ( ) . we hope that the papers in this issue inform and empower the canadian diabetes professional community to continue to broaden our ability to address the important quality of life issues that are a central part of living with diabetes. stay safe. addressing a care gap in type diabetes management: using the diabetes distress scale in a community care setting to address diabetes-related treatment challenges adults with diabetes distress often want to talk with their health professionals about it: findings from an audit of australian specialist diabetes clinics spousal support and relationship happiness in adults with type diabetes and their spouses self-compassion, adaptive reactions and health behaviours among adults with prediabetes and type , type and gestational diabetes: a scoping review diabetes distress in adolescents and young adults living with type diabetes diabetes distress in adults living with type and type diabetes: a public health issue bereavement, grief and adult type diabetes: living with diabetes today an intolerable burden: suicide, intended self-injury and diabetes depression and diabetes distress in south asian adults living in low-and middle-income countries: a scoping review exploring the outcomes of a pilot education program tailored for adults with type diabetes and mental illness in a community mental health care setting efficacy of depression management in an integrated psychiatric-diabetes education clinic for comorbid depression and diabetes mellitus types and mental health professionals have never mentioned my diabetes, they don't get into that": a qualitative study of support needs in adults with type and type diabetes and severe mental illness alcohol use and clinical outcomes in adults in the type diabetes exchange the outcome of structured education in patients with type diabetes mellitus and substance use disorder: a literature review depression in girls with obesity and polycystic ovary syndrome and/or type diabetes association between gestational diabetes and mental illness note from the editors / can key: cord- - bj gr authors: zimmet, p. title: the burden of type diabetes: are we doing enough? date: - - journal: diabetes & metabolism doi: . /s - ( ) - sha: doc_id: cord_uid: bj gr summary increasing levels of obesity, arising from energy-rich diets and sedentary lifestyles, are driving a global pandemic of type diabetes. the prevalence of type diabetes worldwide is set to increase from its present level of million, to million by the end of the decade and to as many as million by . shocking as they are, these figures represent only clinically diagnosed diabetes, and many more cases of diabetes remain undiagnosed and untreated. in addition, up to one-quarter of western populations have impaired glucose tolerance or the dysmetabolic syndrome, which are considered to represent pre-diabetic states. type diabetes is appearing increasingly in children and adolescents, and the frequency of diagnosis of paediatric type diabetes is outstripping that of type diabetes in some areas. the long-term complications associated with type diabetes carries a crushing burden of morbidity and mortality, and most type diabetic patients die prematurely from a cardiovascular event. diabetic patients are more than twice as costly to manage as non-diabetic patients, due mainly to the high costs associated with management of diabetic complications. indeed, diabetes care already accounts for about - % of the total national health care budgets of western european countries. controlling the type diabetes epidemic will require changes to the structure of healthcare delivery. well-resourced interventions will be required, with effective co-ordination between all levels of government, health care agencies, multidisciplinary health care teams, professional organisations, and patient advocacy groups. above all, intervention is needed today. diabetes metab, , , s - s • www.e med.com/dm p zimmet t oday we are seeing a paradox in global public health. in recent decades, we have seen the reemergence of communicable diseases such as tuberculosis, and a new group including hiv/aids, ebola virus and, most recently, the devastating epidemic of severe acute respiratory syndrome (sars). in addition, there is still a global crisis resulting from widespread malnutrition. however, against this background, we are seeing a dramatic rise in prevalence of chronic non-communicable diseases such as type diabetes, cardiovascular diseases, hypertension and obesity in developed and developing nations. there were already signals that diabetes was to become the epidemic of the st century in the early s. at this time, bennett and his colleagues discovered an extraordinarily high prevalence of type diabetes in the pima indians of the usa [ ] , and we reported on the equally high rates of diabetes in the micronesian population of nauru and other pacific island communities [ , ] . over subsequent decades, numerous reports have highlighted the high prevalence of type diabetes in a number of other populations including native americans, afro-americans, and mexican americans in the usa [ ] [ ] [ ] [ ] , native canadians [ ] , australian aborigines and torres strait islanders [ ] , and polynesians in new zealand [ , ] . the prevalence of type diabetes is rising relentlessly around the world (fig ) . current estimates suggest that, globally, the number of persons with diabetes will rise from million in the year , to million by the year , and to million by [ , ] . this rise is predicted to occur in virtually every nation, with the greatest increases expected in developing countries. type diabetes will account for nine patients in every ten of these diagnoses. this explosive increase in the prevalence of type diabetes, and the consequences of its complications and associated disorders, represents the greatest health care challenge facing the world today [ ] . the highest rates of type diabetes occur in native americans and pacific islanders, followed by hispanics or mexican americans, people originating from the indian subcontinent, south east asians and african americans [ , ] . in addition, a relatively high prevalence has been reported from some of the middle east arab states [ , ] , and from disadvantaged minorities in the developed countries, including australia's indigenous population [ , ] . type diabetes affects up to % of adults in native american and pacific island populations [ , , , ] and the years to saw an increase from . % to . % in the prevalence of diabetes among people age - years in the usa [ ] . in china, a prevalence figure of . %, from a survey of , subjects aged - from all parts of the country, was about three-fold higher than prevalence estimates from a decade before [ ] . the type diabetes prevalence in an urban south indian population among individuals aged over years rose from . % in to . % in [ ] , while in denmark, a % rise in diabetes prevalence has been reported over a year period [ ] . in our recent national study in australia, . % of adults were found to have diabetes compared to an estimated . % in [ ] . our studies in mauritius have provided a future guide to the magnitude of the global diabetes epidemic [ ] . the population of this nation are asian indian, creole (black) and chinese, and these three ethnic groups account for over % increasing prevalence of type diabetes by region [ ] . of the world's population. mauritians have a high diabetes prevalence [ ] and a % secular increase occurred between and in mauritian asian indians and creoles [ , ] . the mauritian chinese share this high prevalence [ ] . data showing that the prevalence of type diabetes doubled between and in singaporean chinese, together with the high prevalence in taiwan [ , ] , provide an alarming indicator of the magnitude of the anticipated epidemic in the people's republic of china (prc) [ ] . in the prc, the prevalence of type diabetes was, until recently, less than % [ ] , but recent studies show a three-fold increase in prevalence in certain areas of china within the last two decades [ ] . if china has just % of the prevalence of diabetes in taiwan, the number of individuals with diabetes will increase dramatically from million in to well over million by . diabetes prevalence is currently estimated at . % in the developed world, and forecast to rise to . % by [ ] . developing countries are starting from a lower baseline, at . %, but this is set to increase by more than a third, to . %, in . the lower overall prevalence in developing countries conceals considerable heterogeneity between individual nations. in latin american countries, the crude prevalence of type diabetes for ranges from . % in chile to . % in argentina [ ] and in africa from . % in tanzania to . % in the northern sudan [ ] . in asia, the overall prevalence is low in some countries, such as bangladesh (roughly - %), but higher in others, such as pakistan ( - %) [ , ] . the pacific islands bear an especially heavy burden of diabetes, as described above, with an estimated prevalence of % in kiribati, % in the cook islands, % in fiji, and % in nauru [ ] . increased rates of obesity due to low levels of physical activity and high-energy diets are driving this global epidemic [ ] . for example, between and , the average body weight of men and women in the usa increased by . kg and . kg, respectively, while the prevalence of diabetes increased from . % to . % [ ] . obesity, particularly abdominal obesity, promotes the development of insulin resistance and the dysmetabolic syndrome (also known as the "metabolic syndrome", or "syndrome x") and, ultimately, type diabetes [ ] [ ] [ ] [ ] . approximately one quarter of the population of the developed world are already believed to have the dysmetabolic syndrome [ , ] . impaired glucose tolerance or impaired fasting glucose develop in response to worsening insulin resistance before the clinical diagnosis of type diabetes is made, and signify an increased risk of developing type diabetes [ ] . between % and % of western populations may already have igt [ , ] . for example, the australian diabetes, obesity and lifestyle study (ausdiab) recently surveyed the glycaemic status of a population of , adults [ ] . the overall preva-lence of diabetes was . %, but the combined prevalence of impaired fasting glucose or impaired glucose tolerance was more than twice as high, at . %. these glucose-intolerant, but non-diabetic, individuals represent a reservoir of potential new diabetes cases. approximately - % of individuals with impaired glucose tolerance go on to develop type diabetes each year [ ] . demographic, social and cultural factors profoundly influence the prevalence of diabetes in a developing nation, as shown by recent studies in india. the overall prevalence of diabetes in that country was estimated at . % in the year [ ] . however, a survey in madras, an urban area of southern india, showed that the prevalence of diabetes had risen by % between - and - , and by a further % in the year [ , ] . increasing urbanisation and sedentary work was significantly associated with this increased prevalence [ , ] . indeed, % of urban residents, and only % of rural residents were found to have type diabetes in this survey. south asians who migrate to developed nations face a similar increase in the risk of developing diabetes [ , ] . a greater tendency to insulin resistance is already evident in children of south asian descent in the uk, which is associated with a steeply rising incidence of type diabetes [ , ] . the impact of urbanisation on diabetes prevalence in india is consistent with experience from other cultures, such as australian aborigines, pacific islanders and native americans [ , ] . global estimates predict that the ratio of people with diabetes in urban and rural areas in the developing world will rise from . -fold, at present, to more than -fold in [ ] . other socio-economic factors, particularly poverty, also increase the risk of type diabetes [ ] . patients with a diagnosis of diabetes represent the tip of the iceberg, and a large number of patients with undiagnosed diabetes may also be at risk of adverse clinical outcomes. in the ausdiab study, there was one undiagnosed case for every known case of diabetes [ ] . an observational study carried out in an apparently healthy, elderly ( - years) population in the us revealed that % of the , participants had undiagnosed diabetes. higher estimates have been observed in patients with a previous mi ( %; [ ] ) or awaiting coronary angioplasty ( . %; [ ] ). a study in the uk, which surveyed subjects without known diabetes in an impoverished urban area, illustrates how genetic and socioeconomic factors combine to amplify the problem of undiagnosed diabetes [ ] . the age-adjusted prevalence of diabetes in this population was high in subjects of south asian or african-caribbean descent ( % and %, respectively), as would be expected from earlier studies. however, the age-adjusted prevalence of type diabetes was unexpectedly high ( %) in subjects of european descent. similarly, data from the third us national health and nutrition examination survey suggested that the adult prevalence of undiagnosed type diabetes nationwide was . %, though this concealed wide vari- s diabetes metab, , , s - s • www.e med.com/dm p zimmet ations between men and women and between ethnic groups [ ] . for example, the prevalence of undiagnosed diabetes among middle-aged ( - years) mexican-american men and women was . % and . %, respectively, compared with . % and . %, respectively, for the general population within this age range. there is compelling evidence that undiagnosed diabetes is associated with cardiovascular risk factors characteristic of insulin resistance or the dysmetabolic syndrome, including hypertension and abdominal obesity [ ] [ ] [ ] . the additional increases in metabolic dysfunction associated with westernisation and urbanisation of the developing world, as described above, can only exacerbate this problem in the future. type diabetes mellitus in children, teenagers and adolescents is a serious new aspect of the type diabetes epidemic and is an emerging public health problem of significant proportions [ ] . while, globally, type diabetes is still numerically the major form in children, it is likely that type diabetes is set to be the predominant form within years in many ethnic groups and potentially in europid groups. type diabetes has already been reported in children from japan, the united states, pacific islands, hong kong, australia and the united kingdom [ ] . the prevalence of type diabetes in the general population of the usa has been estimated at . / - year olds [ ] . dabelea et al. have studied pima indian children since the late s, and have demonstrated rising rates of glucose intolerance with time and age, as well as a female preponderance [ ] . from - to - , the prevalence of type diabetes has markedly increased from . % in males and . % in females to . % in males and . % in females. diagnoses of type diabetes now outnumber diagnoses of type diabetes by : in children in parts of japan and china, compared with a ratio of about : of total diagnoses of diabetes in urban usa centres [ , ] . obesity and insulin resistance are driving this explosion of paediatric diabetes, as in adults [ ] . a diagnosis of diabetes has a profound impact on life expectancy, and a patient diagnosed with type diabetes in middle age ( - years) stands to lose as much as years of life expectancy [ ] . given the close association between type diabetes and the cardiovascular risk factors constituting the dysmetabolic syndrome, it is not surprising that most type diabetic patients ultimately die from a cardiovascular cause [ ] . indeed, type diabetes confers the same degree of risk of premature death as a previous myocardial infarction in a non-diabetic subject [ ] . a substantial proportion of type diabetic patients already have diabetic complications at the time of diagnosis of diabetes. for example, retinopathy, peripheral neuropathy and proteinuria were present in %, % and %, respectively, of the newly-diagnosed patients in the uk prospective diabetes study (ukpds) at baseline [ ] . the cost of diabetes in europe -type (code- ) study has investigated the prevalence of diabetic complications in a randomly selected cohort of type diabetic patients. less than half ( %) of the german cohort of , patients (mean age years) did not have diabetic complications, while % had at least two, and % had at least three complications [ ] . cardiovascular complications were present in % of patients, cerebrovascular complications in %, and neuropathy or diabetic foot syndrome, retinopathy and nephropathy were present in %, % and % of patients, respectively. the code- data are consistent with previous estimates of the prevalence of coronary heart disease and other complications in type diabetic patients in various countries (fig ) . the prognosis of type diabetes in patients who already have diabetic complications is extremely poor. a retrospective review of patients referred to a combined diabetesrenal clinic showed that their median survival was only months [ ] . similarly, odds ratios for all-cause and cardiovascular mortality in finnish type diabetes patients with diabetic retinopathy were . and . , respectively, compared with non-diabetic control subjects [ ] . diabetes is expensive to manage, and the per capita costs of managing a diabetic patient are - -fold higher than for a non-diabetic patient [ ] . however, the additional cost burden associated with type diabetes begins long before diabetes is diagnosed. analysis of data from a managed care organisation in the usa showed that the cumulative costs associated with inpatient, outpatient and pharmacy provision for patients with type diabetes were higher, on average, than those incurred by control subjects matched for gender and age for each of the years preceding diagnosis of diabetes [ ] . by the time of diagnosis, the total cost of treatment was $ , higher for a diabetic patient, compared with a control subject (fig ) . costs for the years following diagnosis were higher in diabetic subjects, as would be expected, with a total difference in average total costs of $ , between a type diabetic patient and a matched control subject (fig ) [ ] . most of the cost of managing type diabetes is associated with the management of diabetes-related complications, especially where hospital treatment is required. the ukpds performed separate health economic evaluations, based on the main cohort, who were managed with conventional dietbased treatment or intensive glycaemic management with a sulphonylurea or insulin [ ] , and on overweight patients, who were managed with diet or with intensive metforminbased treatment [ ] . the total costs incurred during years of follow-up are shown in table i . managing complications accounted for about two-thirds of the total costs in the diettreated group of the main cohort, and about three quarters of the costs in diet-treated overweight patients. complications accounted for more than half of the total costs during follow-up even after intensive glycaemic management with a sulphonylurea or insulin (main cohort) or metformin (overweight cohort), which significantly reduced the incidence of microvascular and macrovascular complications, respectively [ , ] . comparing the health economic costs between countries is difficult, because of variations in the costs of services and standard clinical practice, and variations in how data are presented. however, in general terms, the cost of managing complications drives the overall treatment costs in most countries. fig compares the average annual costs of managing a type diabetic patient across europe: in most countries, costs arising from hospital treatment (mainly associated with the management of complications) were markedly greater than out-of- columns show the average of estimates of the prevalence of individual complications for adults with type diabetes presented by amos et al. [ ] . numbers beneath columns show the number of estimates used in each case. chd: coronary heart disease; pvd: peripheral vascular disease. cumulative costs of managing a type diabetic patient and an age-and gender-matched control subject in a managed care organisation over a period of years before (a and b) or after (c and d) the diagnosis of diabetes [ , ] . hospital (ambulatory) costs [ ] . data from the usa, from a model based on the interventions used in the ukpds, show that the annual costs of managing complications in patients receiving diet-based therapy ($ , ) accounted for % of total direct costs of care ($ , ) [ ] . a retrospective analysis of , patients within a managed care organisation in the usa compared the costs of diabetes management in type diabetic patients with no evidence of significant cardiovascular or renal disease ("no complications"), in patients under treatment or investigation for risk factors for cardiovascular or renal conditions ("pre-event"), and in patients with a history of cardiovascular events or clinically significant renal dysfunction ("post-event") [ ] . direct costs were lowest in the "no complications" group (fig ) , and increased in the "preevent" group for men and women. however, the greatest differences in costs were between the "pre-event" and "postevent" groups, with a greater than doubling of costs for patients who developed cardiovascular complications. data are from separate analyses, from the perspective of a healthcare purchaser. all costs are undiscounted direct costs and are in uk £ ( values). additional costs for specialist care were for eye or renal care in lean patients and eye care in overweight patients. the analysis in lean patients presented individual costs from the clinical trial setting and adjusted the total for the routine community care setting; the analysis in obese patients presented all costs after adjustment for the routine care setting, hence na (= not available) for trial costs for overweight patients. the percentage of costs due to complications was calculated using trial costs for lean patients and standard practice costs for overweight patients, for the same reason. total costs (in uk £) associated with type diabetes and its management during years of follow-up in the uk prospective diabetes study [ , ] . direct medical costs per type diabetic patient in some european countries in [ ] . additional treatment costs arising from the development of cardiovascular or renal diabetic complications [ ] . costs are in prices from the perspective of a health care purchaser. patients were stratified as follows. no complication: patients in the analysis either had no history of cardiovascular or renal disease or treatment; pre-event: patients were under treatment with an antihypertensive drug, had made at least two visits to a cardiologist, or had had at least one positive test for microalbuminuria; post-event: patients had suffered at least one major cardiovascular event (e.g. myocardial infarction, stroke, revascularisation, or hospitalisation for congestive heart failure) or had documented clinical renal dysfunction indicated by high serum creatinine measurements. the high prevalence of type diabetes means that the overall costs of managing the disease, including costs arising from managing diabetic complications, are high enough to place a substantial burden on national economies. the total direct healthcare expenditure on the management of diabetes in the usa in was $ billion. of this amount, only $ billion was required for glycaemic management, with $ billion required for the management of complications and other problems related to diabetes [ ] . the total costs of managing type diabetes in europe already range between roughly % and % of national healthcare budgets in europe (fig ) . the burden on some other economies is even higher. for example, diabetes care in mexico accounts for % of the total healthcare budget, which equates to . % of gross domestic product [ ] . moreover, the burden grows heavier as the global epidemic of type diabetes evolves. projections based on the uk diabetic population suggest that the total costs of managing type diabetes will increase from £ . billion in to £ . billion by , an increase of % [ ] (fig ) . national governments have either failed to recognise the future socioeconomic burden of type diabetes or are ignoring it. the global epidemic of type diabetes is already threatening healthcare budgets, and the burden will continue to increase. we should not forget that these prevalence figures relate to people with a clinical diagnosis of type dia-betes. many more people have undiagnosed diabetes, and there is a vast reservoir of people with igt, most of whom will develop diabetes eventually, and who are already at substantial risk of developing cardiovascular disease [ ] . increasing rates of obesity will place ever more people at risk of developing the dysmetabolic syndrome, type diabetes, and cardiovascular disease. the increasing prevalence of type diabetes in children and adolescents underlines the urgency of taking action. the diabetes prevention program has shown us that preventing type diabetes with lifestyle interventions or with pharmacologic therapy is cost-effective in either the european or american settings [ , ] . however, extending these benefits beyond the tightly-controlled structure of a randomised clinical trial will require an unprecedented degree of public health intervention. educating the public on the dangers of obesity and glucose intolerance will certainly be important. some steps in this direction have been made. for example, efforts are underway to improve the lifestyles of school-age children in japan [ ] , and health workers in philadelphia in the usa patrol the streets armed with weighing machines to spread the message of the dangers of obesity [ ] . in finland, a simple questionnaire is being used as a screening tool to identify citizens at risk of type diabetes, who may benefit from further follow-up and intervention [ ] . mounting a successful challenge to the diabetes epidemic, however, will require major alterations to the structure of society. for example, the intervention in finland is being mounted in collaboration with a broad range of governmental agencies and healthcare advocacy groups, as part of a broader strategy dating back several decades [ ] . support from the highest level of governments is also needed, as resources to mount diabetes prevention efforts must be made available, and changes to taxation and reimbursement structures relating to resources for people to improve their lifestyles would also certainly help in the longer term. the rising tide of type diabetes and its complications will place an increasingly heavy burden of morbidity and mortality on patients and their families for decades to come. moreover, the expenditure required to manage these patients will stretch the healthcare systems even of 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descriptive epidemiology of non-insulin dependent diabetes mellitus detected by urine glucose screening in school children in japan us public health and the st century: diabetes mellitus the diabetes risk score: a practical tool to predict type diabetes dehko: development programme for the prevention and care of diabetes in finland key: cord- -me gebvm authors: conway, j.; gould, a.; westley, r.; raju, s.; oklopcic, a.; broadbent, a.; abdelhafiz, ah.; sinclair, aj. title: characteristics of patients with diabetes hospitalised for covid- infection-a brief case series report date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: me gebvm objectives diabetes has been shown to be a risk factor for corona virus disease- (covid- ) infection. the characteristics of patients with diabetes vulnerable to this infection are less specified. we aim to present the characteristics of patients with diabetes admitted to hospital with covid- . design: a retrospective case series. setting: a single clinical centre in the uk. methods we have retrospectively collected the demographics, medical characteristics and outcome of all patients with diabetes admitted to hospital over two-week period with covid- infection. all cases were diagnosed by a reverse transcription polymerase chain reaction (rt-pcr) of pharyngeal and nasal swabs. results a total of covid- patients were admitted during the study period of whom ( . %) patients had diabetes and were included in this case series. there was no significant difference between patients with compared to those without diabetes regarding age, gender or clinical presentation. however, comorbidities were more common in patients with diabetes specially hypertension { % v . %, a difference of . %, % confidence interval (ci) . to . } and chronic kidney disease ( . v . , a difference of % ( . to . ). patients with diabetes were significantly more obese than those without diabetes ( . % v . % a difference of . %, % ci . to . ). about one third ( . %) of patients with diabetes were frail. mean {standard deviation (sd)} duration of diabetes was ( . ) years and mean (sd) hba c was . ( . ) mmol/mol. the use of angiotensin converting enzyme (ace) inhibitors, angiotensin receptor blockers (arbs) and non-steroidal anti-inflammatory drugs (nsaids) was common ( . %, % and . % respectively). there was no significant difference in the outcomes between patients with compared to those without diabetes. conclusion patients with diabetes hospitalised for covid- were significantly more obese and had high prevalence of comorbidities than those without diabetes. other features of patients with diabetes and covid- infection included long duration of diabetes, less tight glycaemic control and common use of ace inhibitors, arbs and nsaids. in december , a pneumonia like illness was first reported in wuhan-china caused by a new coronavirus named corona virus disease- (covid- ) which then spread to cause a global pandemic. in the chinese cohorts, diabetes mellitus appeared to be a risk factor for covid- infection. a meta-analysis of chinese studies to assess the prevalence of comorbidities in , infected patients with covid- , median age . years ( . %) men, diabetes mellitus was the second most prevalent comorbidity ( %) after hypertension ( %) and higher than cardiovascular ( %) and respiratory diseases ( %). also diabetes appeared to be detrimental in predicting worse outcomes. patients infected with covid- who required intensive care unit (icu) treatment were more likely to have diabetes ( . % v . %) compared to those who did not require icu admission. presence of diabetes increased mortality from covid- compared to patients without comorbidities ( . % v . %). in addition to the chinese studies, subsequent international studies have demonstrated that diabetes was a frequent comorbidity and a risk factor for adverse outcomes of covid- infection such as higher rates of icu admissions and refractoriness to anti-viral and anti-inflammatory therapies. [ ] [ ] [ ] [ ] the high risk of covid- infection in patients with combined hypertension and diabetes has been now highlighted in the literature which may be related to the fact that the severe acute respiratory syndrome corona virus- (sars-cov- ) is a cause of endothelial dysfunction and endothelial dysfunction could represent a common link between hypertension, diabetes and covid- . the criteria of patients with diabetes infected with the covid- virus are less specified. in this brief analysis, we report the characteristics of patients with diabetes admitted to hospital in the uk with covid- infection. a retrospective single-centre case report enrolling consecutive patients with diabetes admitted to a district general hospital in the uk with covid- infection from the period of rd of march to th of april . identification of cases with diabetes was verified by the confirmed diagnosis in medical records or by the use of hypoglycaemic medications. identification of covid- status was undertaken in line with public health england (phe) which recommends screening of cases if they present with clinical or radiological evidence of pneumonia, acute respiratory distress syndrome or influenza like illness associated with fever and additional respiratory symptom of persistent cough, hoarseness of voice, nasal discharge, shortness of breath, sore throat, wheezing and sneezing. patients meeting the above criteria then had nasopharyngeal and oropharyngeal swabs sent to our local laboratory for identification of -ncov nucleic acid by reverse transcription polymerase chain reaction (rt-pcr). patients who tested negative by rt-pcr but still have a high index of clinical suspicion were re-tested with a further swab for rt-pcr. medical records were reviewed and patients' demographic, medical and social history was collected. laboratory and radiological information were available in the electronic records. we used a standardised data collection sheet which was used by the authors to capture all the relevant information for each patient. to assess frailty, we used the clinical frailty score (cfs) which classifies patients in a range of very fit (score ) to terminally ill (score ). as the study was retrospective, only available data in medical records were collected but other relevant tests, which are not routinely done in our practice, such as il- and cardiac enzymes were not available and this was a limitation of this study. we used descriptive statistics and calculated % confidence interval for comparison between proportions. patients outcomes such as discharged alive from hospital, died or required icu admission were extracted from electronic medical records. study was approved by our local research and development department. a total of consecutive patients with covid- infection were admitted to hospital during data collection over two-week period, of whom ( . ) patients had diabetes mellitus. demographics of patients with diabetes are displayed in table . all patients were white british, had type diabetes, mean (sd) age . ( . ) years, majority ( patients, %) were ≥ years old and predominantly men ( , . %). source of infection was not very clear in most patients, but no patient reported animal contact, which may suggest that all infections were due to human to human transmission. two patients reported recent travel to spain and to a mediterranean cruise respectively. pre-existing comorbidities were present in % of patients with diabetes with a mean (sd) of . ( . ). all patients with diabetes were either overweight ( , . %) or obese ( , . %). about one third of patients ( , . %) scored ≥ in cfs indicating frailty. mean (sd) duration of diabetes was ( . ) years and about one third of patients ( , . %) were on insulin treatment in addition to oral hypoglycaemic therapy. the use of angiotensin converting enzyme (ace) inhibitors, angiotensin receptor blockers (arbs) and non-steroidal anti-inflammatory drugs (nsaids) was common { ( . %), ( %) and ( . %) respectively}. diabetes tended to be uncontrolled with a mean (sd) hba c of . ( . ) mmol/mol and ( %) patients had hba c > . mmol/mol. common presenting symptoms were fever ( patients, . %), general fatigue ( , . %), cough ( , . %), shortness of breath ( , %), gastrointestinal symptoms ( , . %) and acute confusion ( , . %). one patient presented with diabetic ketoacidosis. in comparison to those without diabetes, patients with diabetes had significantly higher prevalence of hypertension ( % v . %, a difference of . %, % ci . to . ) and chronic kidney disease ( . v . , a difference of % ( . to . ). patients with diabetes were significantly more obese than those without diabetes ( . % v . % a difference of . %, % ci . to . ). majority of patients had abnormal opacifications in the chest x-ray and abnormal systemic laboratory results. comparison of patients with to those without diabetes is summarised in table . all patients with diabetes were treated in acute medical wards and no patients were escalated to icu. supportive care was the only therapy given and no specific antiviral treatment was tried in this cohort. most patients ( , %) had recovered fully and discharged home but ( %) patients have died. the patients who died were not considered for icu admission or escalation plans due to the severity of illness and their comorbidity burden. we present case series with type diabetes admitted to hospital with covid- infection. in the chinese covid- affected patients, diabetes was found to be a risk factor for infection but the characteristics of patients with diabetes vulnerable to this infection have not been specified. our cohort represented . % of all covid- patients admitted during study period. diabetes prevalence has been shown to be % in one study and % in another. , we aimed to collect clinical data on these patients including their clinical presentations, laboratory findings, metabolic profile and their progression. our cohort had a mean age of . years and % of patients were ≥ years, which appears to be older than the chinses cases that have a median age of . years and only . % of them were above the age of years. about half of our patients presented with respiratory symptoms (fever . %, cough . % and shortness of breath %). most prominent was the general nonspecific symptoms of being generally unwell or fatigued ( . %) and gastrointestinal symptoms ( . %). of note, gastrointestinal symptoms were not common in the chinese population for example only . % had diarrhoea. although in another chinese study by wang et al, % of patients initially presented with nausea and diarrhoea - days before the onset of fever and dyspnoea. metabolic profile showed that our patients had uncontrolled and long duration of diabetes. poor glycaemic control may be associated with impairment of the immune response to viral infections and may predispose to potential secondary bacterial infections. the most striking feature was that all patients were either overweight or obese. obesity is a risk factor for severe infection. it has been shown that obesity is associated with the severity and the longer duration of viral infections. central obesity, which is the predominant type in persons with diabetes, is particularly associated with higher risk. the increased secretion of cytokines characterises a chronic low-grade inflammation in central obesity and may induce an impaired immune response. other factors may be related to the fact that obesity may mechanically impair ventilation with reduced aeration of the lung bases that leads to accumulation of secretions and increased risk of infections. similar to our case series, a study from new jersey has demonstrated that covid- infection is associated with hyperglycaemia and obesity. also, in a small study of outpatients with diabetes and covid- , the reported median bmi was . and a range that reaches as high as . kg/m . the prevalence of hypertension was a common finding in our cohort ( patients, %) and most patients used either ace inhibitors or arbs. hypertension was also the most common ( %) comorbidity found in the chinese population infected with covid- . although less prevalent than in our cohort, but this is likely to be due to the fact that all our patients are diabetic and diabetes usually coexists with other cardiovascular diseases especially hypertension which has been shown to be associated with worse outcomes in covid- . [ ] [ ] [ ] [ ] is not clear whether hypertension itself increases the risk of infection or it is due to the fact that many hypertensive patients are using ace inhibitors or arbs. the covid- virus gains entry to the pulmonary cells through binding to membrane ace receptors. the ace inhibitors and arbs appear to increase ace receptors expression and may increase covid- infectivity and illness severity. the concentration of glycated sars-cov- viral particles and glycated ace in the lung epithelium may explain the severity of covid- infection. binding of ace by sars-cov- in covid- also suggests that prolonged uncontrolled hyperglycaemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. on the contrary to this, these medications may reduce the pulmonary and systemic inflammatory response by decreasing cytokines and therefore may be beneficial. recent data from a small italian study of patients with covid- has demonstrated that anti-hypertensive therapy of ace inhibitors, arbs or calcium channel blockers did not affect the outcome. therefore, this issue remains needing further exploration in future larger studies. we did not demonstrate higher mortality in our diabetes cohort compared to those without diabetes. this could be due to the small study sample. also our cohort, although had overall less tightly controlled diabetes, their admission random blood glucose was not grossly elevated. data from the us showed that mortality rate was higher for patients with uncontrolled hyperglycaemia compared to those without hyperglycaemia. also, hyperglycaemia related mortality was . % compared to . % for patients with diabetes but no hyperglycaemia suggesting that hyperglycaemia itself, rather than diabetes, played a crucial role in adverse outcome. also, a recent study has shown that insulin infusion to tighten blood glucose control in the immediate post-admission period was associated with a significant reduction of inflammatory cytokines and pro-coagulant state which may reduce the risk of disease progression. about one third of our cohort was frail. frailty is a syndrome that is characterised by multisystem dysregulation that leads to reduced physiologic reserve and increased risk of adverse health outcomes. dysregulation in the innate and adaptive immunity also leads to chronic inflammation, increase in inflammatory markers and increased susceptibility to sever infections. in a recent multicentre european cohort study, frailty, assessed by cfs, proportionately predicted mortality. a limitations of this study is the small number of population included which may limit its generalisability. also, no patients in our cohort was admitted to icu, which may be just a reflection of the small study sample. also of note, the cause of death in patients who died in this cohort was severe sepsis and these patients were not considered for further escalation to icu treatment due to the perceived poor prognosis of their high comorbidity burden. patients with diabetes hospitalised for covid- were significantly more obese and had higher prevalence of comorbidities, in particular hypertension and chronic kidney disease, than those without diabetes. other features of patients with diabetes and covid- infection include long duration of diabetes, less tight glycaemic control and the common use of ace inhibitors, arbs and nsaids. preventative measures should continue to develop to improve the metabolic profile of people with diabetes to reduce their risk of infection. overweight and obesity appeared to be a striking feature affecting all patients in this cohort. it is not yet clear whether the new weight reducing hypoglycaemic therapy will have an effect in reducing risk of infections in people with diabetes. although a specific anti-viral drug is urgently required, a multi-target agent is also required to help regulate the dysregulated neuro-endocrine-immune system that is common in metabolic diseases including diabetes, cardiovascular disease, atherosclerosis, insulin resistance, hypertension, dyslipidaemia and obesity. research is urgently required to develop protective vaccination. due to vulnerability of the characterised group in our cohort these criteria should be considered in future vaccination programmes. the viral entry into the cell membrane through the ace receptors needs further exploration and future trials are needed to investigate the role of the current blockers of angiotensin aldosterone pathway in viral infections. the role of hypoglycaemic medications such as dipeptidyl peptidase- (dpp- ) inhibitors, which may act as receptor for covid- and the glucagon-like peptide- receptor agonist (glp- ra), that may reduce inflammation, will need further investigation. , key points  patients with diabetes hospitalised for covid- are significantly more obese and had higher prevalence of comorbidities, in particular hypertension and chronic kidney disease, compared to those without diabetes. ci=confidence interval, copd=chronic obstructive pulmonary disease, cvd=cardiovascular disease, ckd=chronic kidney disease, cld=chronic liver disease, cfs=clinical frailty score, bmi=body mass index, aki=acute kidney injury, crp=c-reactive protein, cxr=chest x-ray, icu=intensive care unit. *significant difference. the continuing -ncov epidemic threat of novel coronaviruses to global health -the latest novel coronavirus outbreak in wuhan, china prevalence of comorbidities in the novel wuhan coronavirus (covid- ) infection: a systematic review and meta-analysis clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan the novel coronavirus pneumonia emergency response epidemiology team. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) -china impact of diabetes mellitus on clinical outcomes in patients affected by covid- outcomes in patients with hyperglycemia affected by covid- : 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patients with viral pneumonia: the mulbsta score the effect of frailty on survival in patients with covid- (cope): a multicentre, european, observational cohort study comorbid diabetes results in immune dysregulation and enhanced disease severity following mers-cov infection coronavirus infections and type diabetes-shared pathways with therapeutic implications key: cord- - qarauys authors: assaloni, roberta; carnevale pellino, vittoria; puci, mariangela v.; ferraro, ottavia e.; lovecchio, nicola; girelli, angela; vandoni, matteo title: coronavirus disease (covid- ): how does the exercise practice in active people with type diabetes change? a preliminary survey date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: qarauys abstract aims coronavirus disease (covid- ) could lead persons with pre-existing medical conditions to severe respiratory infections. the italian government introduced quarantine to limit viral transmission. this measure could lead people with type diabetes (pwt d) to disrupt daily care routine including pa practice with difficulties in glycemia management. this study aims to explore pa level in pwt d before and during quarantine and to describe variation in glycemia values. methods an online survey investigating medical factors and the perceived and pa level in pre-established period before and after the introduction of quarantine was developed. comparison between pre and post quarantine was assessed by wilcoxon signed ranks test for continuous variables. results a total of subjects satisfied the eligibility criteria ( . % males, . ± . years). we found a decrease of pa level (godin scale score ± . vs . ± . points), steps number and minutes of exercise (respectively . ± vs . ± . and ± vs ± ) and an increase of glycemia values ( . ± . mg/dlvs . ± . mg/dl) conclusions pwt d reported a decrease in exercise and worst glycemia. although pwt d tried to remain active, their pa level was inadequate to prevent glycemia rising. the difficult to maintain a glycemic control could expose patients to diabetes complications and to an higher risk to counteract infections. the on-going coronavirus disease , an acute infectious respiratory that could lead to a severe pneumonia till to death, has become the world's leading health headline causing public concerns [ , ] . on january , , the world health organization (who) declared that the new coronavirus outbreak is a public health emergency [ ] . further, on february , , the covid- expanded in italy causing the largest and deadly epidemic in the country [ ] . who warned that the most at-risk populations are older and people with pre-existing medical conditions such as high blood pressure, heart disease, lung disease, cancer and diabetes [ ] . in particular, people with type (pwt d) and poor glucose control, in particular high glycated hemoglobin (hba c) or/and insulin resistance, showed higher risk to counteract infections due to the impaired body immune response, this also holds true with covid- [ , ] . for this reason, pwt d should manage blood glucose levels with frequent glycemia controls and subsequent insulin delivery adaptations and improving their life style to prevent serious illness [ ] . moreover, it seems that the routine care of diabetes that included also diet and physical activity (pa) were disrupted during the current pandemic, these may contribute to worsening outcomes [ ] [ ] [ ] . in accordance to istituto superiore della sanità (iss), the italian government implemented extraordinary measures to limit viral transmission throughout people and the territory, imposed national quarantine, reduced social interaction and travelling and "stay at home" as a basic means of limiting people's exposure to the virus [ ] . unfortunately, the mandated restrictions on travel and on participating in outdoor activities, including regular pa and exercise, inevitably disrupted the daily routine activities of millions of people [ , ] . although containing the virus spread remains a priority, it is also necessary to act on multiple aspects of public health. unfortunately, few public health guidelines for the public in terms of maintaining daily exercise or pa routines were developed [ ] . pwt d have been advised to follow general guidance on risk reduction, including social distancing and were emphasized the importance of good glycemic control. the major strategies to control glycaemia levels and reduce the risk of hyper or hypoglycemia are: more frequent blood glucose monitoring, diet and maintain the regular practice of pa [ , [ ] [ ] [ ] [ ] . we hypothesize that quarantine reduced social and environmental exposure and consequently pa practices (gym and outdoor activities) with possible health impairment. in particular, in pwt d, even in active people, the reduction of pa could have altered euglycemia maintenance. regular and safe exercise practice should preserve good psycho-physical wellbeing and the protective effects of it. despite the closure of green areas, gyms and swimming facilities, we assume that an increased use of technology, such as specific training channels, applications and resources posted on social media could help people to train at home. the aim of this study is to explore the pa level in italian people with type diabetes before and after the national quarantine introduced to contrast covid- disease and describe variation in glycemia values. we conducted an observational study. pwt d were recruited through an online survey developed by sport scientists and diabetologists through surveymonkey software (surveymonkey inc , california, usa) in italy. the inclusion criteria for pwt d were age> years, hba c < mmol/mol (< %) and the capacity to understand italian language. the exclusion criteria were uncontrolled diabetes, comorbidities that do not allow exercise practice, ongoing covid- infection and cognitive impairments. participants were asked to fill out a survey consisting of multiple features referred to two periods: before the outbroken of covid- disease and after the introduction of national quarantine. all the participants were asked to completed the written informed consent to the threat of data before to be enrolled in the study: "we guarantee the confidentiality of the information anthropometric characteristics such as body weight (kg) and height (m), socio-demographical outcomes and medical factors such as the duration of disease (yrs) and the self-reported values of the last (mmol/mol;%) hba c were collected by online survey to describe the sample. pa level was investigated into pre-established days before the outbreak of covid- disease and after the introduction of national quarantine . the perceived pa level was explored through the godin-leisure time exercise questionnaire [ ] . the godin-leisure time exercise questionnaire is a self-reported questionnaire that investigated leisure activity during a day period of different intensity exercise (strenuous, moderate and light). the weekly leisure activity score was previously described by godin et al ( ) . to obtain pa level, we ask to report the number of steps and minutes of exercise of subjects with an activity tracker (at). patients reported their glycaemia values (mg/dl) through the mean values ( days) showed by system connected to continuous glucose monitoring in the two periods of the study: two weeks before and two weeks after quarantine beginning. then, the modifications of subjective perception of metabolic compensation (optimal, good or low) before quarantine while glycemia trend (ameliorated, stable, worsted with glycemia rising and/or glycemia fluctuation) and changes in insulin delivery (stable, increase or decrease) during quarantine were investigated. quantitative variables were expressed by mean ± standard deviation (sd) and qualitative variables by frequencies or percentage as appropriate. the assumption of normality of data was tested by shapiro-wilk test. comparison between pre and during quarantine was assessed by a paired t-test and wilcoxon signed ranks test for continuous variables. a p-value of less than . was considered statistically significant. all analyses were performed using stata software. a total of pwt d answered to the survey. the quality control of data was made in order to evaluate discrepant responses, missing data and ineligibility criteria. a total of subjects satisfied the eligibility criteria ( figure ). the . % of sample was males, the mean age was . ± . years. the mean height and weight were . ± . m and . ± . and the mean bmi was ± . kg/m (table ). in the period before the quarantine . % practiced exercise in different modalities ( . % in autonomy), during the quarantine . % maintained exercise in autonomy. godin scale score showed an active pa level (score > points) both in pre and during quarantine, but during quarantine we observed a significant decrease (respectively ± . points vs . ± . points; p< . ).we observed, also, a significant increase in the mean values of glycemia during the quarantine (pre quarantine . ± . mg/dl vs during quarantine . ± . mg/dl; p<. ) (table ) . further, we investigated the variation of perceived metabolic compensation and the insulin delivery finding that during the quarantine the . % of pwt d perceived worst metabolic compensation due to increased glycemia mean values and glycemic variability; . % of pwt d had to modify the insulin delivery and, in particular % of them, had to modify both the basal and rapid dosage. (data not shown). the sub-sample of subject with at confirmed a low pa level during national quarantine, in fact, we found a decrease in steps number and in minutes of exercise (respectively . ± vs . ± . steps number; ± vs ± minutes of exercise; p<. ). also glycemia and gss follow the same trend of whole sample (table ). the covid- pandemic is considered the worst public health concern in the last decades that resulted the largest and severest measures to contrast the diffusion of the disease [ ] . people of all ages risk to counteract this virus but the most at-risk populations are older and people with pre-existing medical conditions such as diabetes [ ] . people with uncontrolled type diabetes showed higher risk to get infections so they should manage blood glucose levels as close as possible to their goal to prevent serious complications related to the disease such as onset and progression of microvascular (neuropathy, nephropathy and retinopathy) and macrovascular complications [ ] . the movement limitations imposed by italian government created difficulties to patients in maintaining routine care with limitation of option of pa and more complex management of diabetes [ , ] . in our study, pwt d reported a significant decrease both perceived and measured pa level and an increase of glycemia values during the national quarantine. in particular, more than % of patients reported a worst perceived of metabolic compensation and more than % of patients underlined a worst glycemia management and the necessity to modified insulin delivery. many researches supported the role of pa practice to maintain the euglycemia state and to reduce the glycemic rebound helping patients to better manage diabetes [ , , , , ] . the increased difficult to maintain good glycemic control could expose patients to general diabetes complications and, in particular, to higher risk to counteract infections. diabetologists had to advise patients to ameliorate diabetes control and suggested the strategies to pursue this aim. however, in this period, the entire health system was overloaded and pwt d have less possibilities to interact with clinicians with a possible repercussion on disease and therapy management. an encouraging aspect that emerge from our data is that pwt d tried to remain active in the quarantine period but, nevertheless their pa level was adequate, it seems that it was not sufficient to totally prevent glycemia rising. the main training methods used by pwt d trough application or video in internet and an implementation of this "tele-exercise" provided by sport specialist could help patients to remain active in a totally safe way. training is usually seen as a protective factor but, in this situation, it was almost halved and pwt d, to control adverse glycemic events, had to modify therapy increasing both rapid both basal insulin deliveries. in particular, when lifestyle decrease from active to sedentary, clinicians suggest pwt d to improve basal and bolus insulin delivery from to % and to adequate doses after - days. mean glycemia level increased according to pwt d perceptions of increased glycemic variability. rise of glycaemia and glycemic variability are indicators of poor glycemic control that usually restore in a long period. [ , ] . we are conscious of some limitations of this study. primary, due to the impossibility to recruit people in the quarantine, people responded on a voluntary base to the survey. this caused a bias to the sample, in fact, the majority of responders were active people. however, this aspect, enforce the validity of the results because, also in a sample of trained people, we found alterations in glycemia trend and difficulties in therapy management. furthermore, pa assessment could be affected by some bias due to self-reported questionnaires (wrong perception of actual pa) and accuracy of smartwatches. nevertheless, the values of both self-reported and objectively measured pa data showed the same trend of reduction of exercise. in conclusion, training level and performance are destined to decreased during the quarantine so it is conceivable that, also when usual training routine will be resumed, health benefits will be less substantial. for this reason, guidelines for pwt d on exercise during quarantine should be established. in our opinion and in accordance with previous studies, to face the less possibilities to exercise, aerobic exercise of moderate to vigorous should be performed with an accurate control of heart rate and circuit or resistance training should be preferred to classical body weight exercise [ ] [ ] [ ] [ ] . a new coronavirus associated with human respiratory disease in china the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak who. #covid coronavirus disease covid- trend estimation in the elderly italian region of sardinia prevalence of comorbidities in the novel wuhan coronavirus (covid- ) infection: a systematic review and meta-analysis covid- and diabetes mellitus: unveiling the interaction of two pandemics covid- : consider cytokine storm syndromes and immunosuppression perspective : covid- pandemic , corona viruses , and diabetes mellitus ranganath muniyappa and sriram gubbi clinical endocrine section , diabetes , endocrinology , and obesity branch , national institute of diabetes and digestive and kidney diseases myokines, physical activity, insulin resistance and autoimmune diseases . &atitle=myokines% c+physical+activity% c+insulin+resistance+and+autoimmune +diseases&stitle=immunol.+lett.&title=immunology+letters&volume= &issue=&spage= &epage= & aulast=d%c %adaz&aufirst=buenaventura+brito&auinit=b.b.&aufull=d%c %adaz+b.b.&coden=imle d&isbn=&pages= - &date= &auinit =b&auinitm=b effects of acute and chronic exercise on immunological parameters in the elderly aged: can physical activity counteract the effects of aging? . &atitle=effects+of+acute+and+chronic+exercise+on+immunological+parameters+in +the+elderly+aged% a+can+physical+activity+counteract+the+effects+of+aging% f&stitle=front.+im munol.&title=frontiers+in+immunology&volume= &issue=oct&spage=&epage=&aulast=sellami&aufir st=maha&auinit=m.&aufull=sellami+m.&coden=&isbn=&pages=-&date= &auinit =m&auinitm= role of physical activity in diabetes management and prevention covid- and italy: what next? guidelines for exercise testing and prescription acsm guidelines for exercise testing and preescripción wuhan coronavirus ( -ncov): the need to maintain regular physical activity while taking precautions biochemical, physiological and psychological changes during endurance exercise in people with type diabetes exercise for type diabetes mellitus management: general considerations and new directions glycemic control during consecutive days with prolonged walking exercise in individuals with type diabetes mellitus exercise management in type diabetes: a consensus statement impact of physical activity on glycemic control and prevalence of cardiovascular risk factors in adults with type diabetes: a cross-sectional multicenter study of , patients physical exercise-induced myokines and muscle-adipose tissue crosstalk: a review of current knowledge and the implications for health and metabolic diseases . &atitle=physical+exercise-induced+myokines+and+muscle-adipose+tissue+crosstalk% a+a+review+of+current+knowledge+and+the+implications+for+health+an d+metabolic+diseases&stitle=front.+physiol.&title=frontiers+in+physiology&volume= &issue=sep&sp age=&epage=&aulast=leal&aufirst=luana+g.&auinit=l.g.&aufull=leal+l.g.&coden=&isbn=&pages=-&date= &auinit =l&auinitm=g physical activity level and exercise in patients with diabetes mellitus. rev da assoc médica bras effects of high-intensity interval exercise versus moderate continuous exercise on glucose homeostasis and hormone response in patients with type diabetes mellitus using novel ultra-long-acting insulin sprint training increases muscle oxidative metabolism during high-intensity exercise in patients with type diabetes interleukin- blockade ameliorates the effect of exercise on cardiac fat in abdominally obese individuals resistance versus aerobic exercise acknowledgements: we would like to thank aniad italia, associazione diabetici della provincia di brescia and sweet team aniad fvg for the great support and help to develop the survey to people. key: cord- -c jm g authors: zhang, yan; cui, yanhui; shen, minxue; zhang, jianchu; liu, ben; dai, minhui; chen, lingli; han, duoduo; fan, yifei; zeng, yanjun; li, wen; lin, fengyu; li, sha; chen, xiang; pan, pinhua title: association of diabetes mellitus with disease severity and prognosis in covid- : a retrospective cohort study date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: c jm g abstract the novel coronavirus disease (covid- ) emerged in wuhan, china, and was characterized as a pandemic by the world health organization. diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with covid- has not been reported yet. methods in this cohort study, we retrospectively reviewed consecutive hospitalized covid- patients with or without diabetes at the west court of union hospital in wuhan, china, recruited from january to february , . the clinical features, treatment strategies and prognosis data were collected and analyzed. prognosis was followed up until march , . results of the hospitalized patients ( with diabetes) with covid- , the median age was years (range - ), and ( . %) were male. common symptoms included fever ( . %), dry cough ( . %), polypnea ( . %), and fatigue ( %). patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme mb at admission compared with those without diabetes. covid- patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death ( . % vs. . %). cox proportional hazard model showed that diabetes (adjusted hazard ratio [ahr]= . ; % confidence interval [ci]: . , . ) and fasting blood glucose (ahr= . ; % ci: . , . ) were associated with the fatality due to covid- , adjusting for potential confounders. conclusions diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with covid- . since december , china has been experiencing an outbreak of pneumonia with a novel coronavirus [ ] , which was officially named as severe acute respiratory who characterized covid- as a pandemic, as it has spread rapidly throughout china and more than countries in the following months after the outbreak, causing more than , confirmed cases and thousands of deaths by march , . sars-cov- belongs to the subgenus sarbecovirus (β-cov lineage b), and shares % of sequence with severe acute respiratory syndrome coronavirus (sars-cov), but only % homology with middle east respiratory syndrome coronavirus (mers-cov) [ , ] . china has had a climbing prevalence rate of diabetes in recent decades. according to the latest nationally representative cross-sectional survey among participants in in mainland china, the overall prevalence of diabetes was . % in adults and . % in the elderly [ ] . patients with diabetes are more susceptible to be infected by bacteria, viruses, and fungus than individuals without diabetes owing to relatively lower immune function [ , ] . as a result, these patients might be at an increased risk of sars-cov- infection and consequently poor prognosis. although many studies have described the clinical characteristics of covid- , so far [ , , , ] , information with respect to diabetes among these patients, has not been well characterized yet. in the current study, we retrospectively reviewed the clinical data of patients with laboratory-confirmed covid- , and compared the differences in clinical characteristics, laboratory markers, treatment strategies, and short-term prognosis including death between patients with and without diabetes. we hope that these findings will provide new insights into the risk stratification, disease management, and therapeutic strategies for covid- patients with diabetes. this was a retrospective cohort study among patients with covid- demographic, clinical features, laboratory and radiological findings, treatment strategy, and short-term prognosis data of the patients were obtained from their medical records. clinical outcomes were followed up to march , . all the data was checked by two senior physicians (p.p and j.z). all the patients enrolled in this study were laboratory-confirmed covid- patients, and the diagnostic criteria of covid- was based on the positive detection of viral nucleic acids. the severity of covid- was defined based on the diagnostic and treatment guidelines (version - ) by the national health committee of china. severe subtype was defined if a patient met one of the following criteria: ) respiratory distress with respiratory frequency ≥ /min; ) pulse oximeter oxygen saturation ≤ % at rest; ) oxygenation index (artery partial pressure of oxygen/inspired oxygen fraction, pao /fio ) ≤ mmhg. critically ill subtype followed the criteria mentioned above, and met one of the following criteria: ) needs mechanical ventilation due to respiratory failure; ) shock; ) combined with multiple organ failure requiring transfer to intensive care unit (icu). pharyngeal swab specimens were collected from each patient for viral nucleic acid detection of sars-cov- using a real-time reverse-transcriptase polymerase-chainreaction (rt-pcr) assay as previously described [ ] . the viral nucleic acid testing all data was reviewed and transferred to the standardized forms from the electronic medical records in the hospital, including case report forms, nursing records, laboratory and radiological findings. two senior physicians (p.p and j.z) independently reviewed the data. information on demographic data, symptoms, preexisting chronic comorbidities, computed tomographic images of chest, laboratory results were collected. all treatment strategies were recorded during the hospitalization, such as antiviral therapy, antibiotic therapy, use of corticosteroid, and respiratory support. the time from the onset of the illness to the hospital admission was also recorded. patients with diabetes were identified based on the patient's documented medical history and guidelines for the prevention and control of t d in china [ ] . cardiovascular disease including coronary artery disease, congestive heart failure, or a history of myocardial infarction were included; reports of isolated hypertension were not included. chronic pulmonary disease, chronic obstructive pulmonary disease (copd), allergic airway disease or the use of supplemental oxygen at home was included. the presence of ards was designated by the berlin definition [ ] . cardiac injury was identified when the serum level of hypersensitive cardiac troponin i (hstni) was above the upper limit of the normal range or new abnormalities were shown in electrocardiography and echocardiography [ ] . acute kidney injury (aki) was classified on the basis of the highest serum creatinine level or urine output criteria based on kdigo clinical practice guideline for aki [ ] . prognosis was defined based on the patient being discharged from hospital, not discharged yet, or death during hospitalization. the follow-up observation was conducted before march , . continuous variables were shown as median and interquartile range (iqr), and compared by the mann-whitney test since most laboratory data was with skewed distribution. categorical variables were presented as counts and proportions, and compared by chi-square test or fisher's exact test. the cox proportional hazard model was used to determine the associations of diabetes and fbg with fatality of covid- , and adjusted for potential confounders. adjusted hazard ratio (ahr) with % confidence interval (ci) was presented as the effect size. all statistical analyses and graphs were generated and plotted using the graphpad prism version . software (graphpad software inc) or spss version . (ibm, united states). a p value < . was considered statistically significant. a total of consecutive laboratory-confirmed patients with sars-cov- infection were included and analyzed in the study, and % of them had diabetes. demographic and clinical characteristics of the patients on admission were summarized by diabetes in the laboratory and radiological findings on admission of the covid- patients with or without diabetes were presented in interestingly, decreased eosinophil count was also common in these patients ( %), but no significant difference in eosinophil count and the ratio of patients with decreased eosinophil count was found in patients with or without dm. besides, a positive correlation between eosinophil and lymphocytes numbers on admission was observed (data not shown), which was consistent with previous study [ ] . other laboratory findings showed no significant differences between the two groups of patients with respect to serum levels of crp, pct, and ldh, but covid- patients next, we compared the severity, treatment, and short-term prognosis of the covid- patients with and without diabetes in table . compared with non-diabetes subjects, patients with diabetes were more likely to develop severely or critically ill subtypes (p= . ) with more complications including acute respiratory distress ( . % vs. . %, p= . ), acute cardiac injury ( . % vs. . %, p= . ), and had more antibiotic therapy ( . % vs. . %, p= . ), non-invasive and invasive mechanical ventilation (p= . ). as of march , , only . % patients were discharged from the hospital. patients with diabetes had a higher fatality rate than those without diabetes ( . % vs. . %, p= . ). table . analysis of severity, treatment and prognosis of covid- patients. to further assess the association of diabetes and fbg with the fatality of covid- , cox proportional hazard model was carried out, and the results ( in this retrospective cohort study, we characterized covid- patients with respect to demographics, clinical features, preexisting chronic comorbidities, treatment, and short-term prognosis. we found that covid- patients had a relatively high proportion ( %) of diabetes, and demonstrated that diabetes was associated with alterations in laboratory markers, more severe clinical subtypes at the time of presentation, and worse prognosis compared to those without diabetes, after to the best of our knowledge, this study was the first to investigate the clinical characteristics and prognosis of covid- patients with diabetes. the prevalence of diabetes mellitus is sharply climbing in china in the last few decades. according to the latest nationally representative cross-sectional survey in mainland china in , the estimated prevalence of diabetes in elderly participants (≥ years old) was . % [ ] . previous studies reported % to % prevalence of diabetes in covid- patients [ , , , ] . here, we reported a higher prevalence rate of diabetes in these patients, which might be due to the larger proportion of geriatric patients infected by sars-cov- in our study. the median age of all the participants was years old, which was older than the data previously reported [ , , ]. in the current study, . % of the patients were male, and the percentage is similar to that reported by wang et al [ ] and zhang et al [ ] . besides diabetes mellitus, hypertension ( . %) and cardiovascular diseases ( . %) were also common underlying chronic illness, and covid- patients with diabetes seemed to have more comorbidities of cardiovascular diseases and chronic kidney diseases in the current study. the laboratory findings on admission showed that leucocytes and neutrophils count and the proportion of increased leucocytes were higher in covid- patients with diabetes than those without, which might be explained by the fact that patients with diabetes were more susceptible to pathogens after a viral infection due to lower immune function. during hospitalization, patients with diabetes were more likely to receive antibiotic therapy as well. decreased lymphocytes count and eosinophil count were also common in these patients; this was consistent with the results of previous studies [ ] . however, no significant differences were found in the cell counts and percentage lymphocytes and eosinophil count between covid- patients with or without diabetes. the data revealed that covid- patients with diabetes had a higher nlr, which was recently reported as a predictor of severity of covid- in the early stage [ ] . we found that covid- patients with diabetes were more likely to develop severely or critically ill subtypes, including more complications with ards, acute cardiac injury, resulting in receiving more antibiotic therapy and mechanical ventilation. cox regression model indicated that both diabetes and fbg level on admission were independent predictors for the fatality of covid, after adjusting for potential confounders. based on these findings, we diligently concluded that diabetes was associated with deteriorating disease severity and worsening prognosis in patients with covid- . this is the first report to demonstrate that diabetes was associated with aggravating disease severity and poorer prognosis in covid- patients. an increasing number of studies have shown that patients with diabetes have had higher mortality and morbidity of severe medical illness, such as myocardial infarction. high fbg plays an independent predictive role in hospitalized critically ill patients than those without diabetes as well [ , , ] . diabetes has also been identified as a significant risk factor for severe disease following respiratory tract infections [ ] . several studies demonstrated that diabetes was associated with increased risks of severity and mortality after sars-cov and mers-cov infection [ , , , ] , and fbg level was an independent predictor for fatality in patients with sars [ ] . a very recent study indicated that well-controlled glycemia was associated with markedly improved outcomes of covid- patients combined with pre-existing t d [ ] . additionally, we found that covid- patients with diabetes also had preexisting cardiovascular disease, and were more susceptible to having acute cardiac injury during hospitalization, which might increase the possibility of short-term poor prognosis in patients with diabetes after sars-cov- infection. previous studies reported that patients with diabetes who received intensive glycemic control had lower risk of cardiovascular events [ ] . nevertheless, we could conclude that diabetes and fbg were independent predictive risks for poor outcomes in covid- patients after adjusting those confounders and mediators. diabetes results in a proinflammatory homeostatic immune response skewed toward helper t cell (th ) and t cells and a decrease in regulatory t cells (treg) [ ] . immune dysfunction of diabetes alone or following infection has been reported for a wide variety of immune cells, not just macrophages, monocytes and cd + t cells [ ] . a recent study reported the number of total t cells, cd + and cd + t cell subsets were substantially reduced and functionally exhausted in covid- patients, especially among geriatric and critically ill patients who required icu admission [ ] . kulcsar ka et al showed that diabetic mice presented a prolonged phase of severe disease and delayed recovery after mers-cov infection, which was attributed to dysregulated immune response with lower inflammatory monocytes/macrophages and cd + t cells [ ] . thus, optimal management of diabetes and intensive glycemic control may help prevent the occurrence of life-threatening infections and complications associated with diabetes mellitus, as well as to combat the increased susceptibility of infections due to impaired cellular and humoral immunity. our study was subject to a few limitations that should not go unnoticed. firstly, this study was a retrospective study, so we included a very small proportion of patients with laboratory-confirmed sars-cov- infection in wuhan. berkson bias might be introduced since asymptomatic patients and those with mild symptoms were less likely to be enrolled. secondly, due to the massive number of patients and the lack of medical resources, the interval from the onset of the illness to hospital admission was more than days for most patients, which could further complicate and deteriorate their condition. nevertheless, patients with diabetes had a similar interval from onset of illness to hospital admission compared with those without diabetes. thirdly, at the time of the study submission, most of the patients were not discharged yet, and the final survival outcome could not have been determined, and the long-term prognosis was not observed. fourthly, other diabetes-associated parameters, including glycated hemoglobin, "peak levels" or "postprandial levels" of plasma glucose could better reflect the association of plasma glucose control and mortality in patients with covid- if that data was available. in the current study, we demonstrated that diabetes mellitus is associated with greater disease severity and poorer short-term outcomes including death. stronger personal prophylactic strategies are advised for patients with diabetes, and more intensive surveillance and treatment should be considered when they are infected with sars-cov- , especially for geriatric patients or those with preexisting comorbidities. the authors declare no conflict of interests. < . ahr, adjusted hazard ratio; ci: confidence interval. dm: diabetes mellitus; fbg: fasting blood glucose. a adjusted for age. b additionally adjusted for preexisting cardiovascular disease and chronic kidney disease. c additionally adjusted for inflammatory biomarkers (leucocytes, neutrophils, lymphocyte, eosinophil, nlr, neutrophil-to-lymphocyte ratio; c-reactive protein, procalcitonin). epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding who. middle east respiratory syndrome coronavirus prevalence and ethnic pattern of diabetes and prediabetes in china in role of t lymphocytes in type diabetes and diabetesassociated inflammation immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections clinical features of patients infected with novel coronavirus in wuhan, china clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in clinical characteristics of novel coronavirus infection in china clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected: interim guidance clinical features and progression of acute respiratory distress syndrome in coronavirus disease guidelines for the prevention and control of type diabetes in china acute respiratory distress syndrome: the berlin definition association of cardiac injury with mortality in hospitalized patients with covid- in wuhan, china kidney disease: improving global outcomes (kdigo) acute kidney injury work group. kdigo clinical practice guideline for acute kidney injury clinical characteristics of patients infected with sars-cov- in wuhan neutrophil-to-lymphocyte ratio predicts severe illness patients with novel coronavirus in the early stage hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes intensive insulin therapy in the critically ill patients outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control the etiology of lower respiratory tract infections in people with diabetes plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with sars clinical presentation and outcomes of middle east respiratory syndrome in the republic of korea risk factors for severity and mortality in patients with mers-cov: analysis of publicly available data from saudi arabia association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes intensive glucose control in patients with type diabetes - -year follow-up reduction and functional exhaustion of t cells in patients with coronavirus disease comorbid diabetes results in immune dysregulation and enhanced disease severity following mers-cov infection pt (sec), median (iqr) dm, diabetes mellitus; iqr, interquartile range; wbc, white blood cell; nlr, neutrophil-to-lymphocyte ratio; crp, c-reactive protein ldh, lactate dehydrogenase; fbg, fasting blood glucose crea, serum creatine; bun, blood urea nitrogen; ck-mb, creatine kinase isoenzyme mb we thank all the patients involved in the study. we thank all the medical staff who are fighting against this public crisis. we also thank dr. abira afzal choudhry for proofreading this paper. key: cord- -dhl ynrc authors: unnikrishnan, ranjit; misra, anoop title: infections and diabetes: risks and mitigation with reference to india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: dhl ynrc background and aims: the link between diabetes and increased risk of infectious disease has long been recognized, but has re-entered sharp focus following the covid- pandemic. methods: a literature search was conducted in pubmed for articles in english on diabetes and infection. results: diabetes predisposes to infections through alterations in innate and acquired immune defenses. outcomes of infection are worse in people with uncontrolled diabetes, and infection can worsen hyperglycemia in hitherto well controlled diabetes (bidirectional relationship). diabetes does not increase the risk of infection with covid- per se, but predisposes to severe disease and poor outcomes. covid- has also been linked to deterioration of glycemic control as well as new-onset diabetes. conclusions: clinicians caring for people with diabetes should be aware of the increased risk of infections in this population, as well as the possibility of worsening hyperglycemia. a holistic approach with frequent monitoring of blood glucose levels and appropriate titration of medications, along with close attention to nutritional status, is essential to ensure the best possible outcomes. infectious disease is an important, yet oft-neglected corollary of uncontrolled diabetes mellitus. in the pre-insulin era, most deaths among individuals with type diabetes and many among type diabetes occurred as a result of uncontrolled infection. it is a matter of concern that even today, infections continue to cause significant morbidity and mortality in patients with diabetes, notwithstanding the recent advances in antihyperglycemic and antimicrobial therapeutic options. in this short review, we will review the mechanisms underlying increased susceptibility to infection in diabetes and briefly discuss the clinically relevant infections found in patients with diabetes, with particular reference to the ongoing covid- pandemic. indian situation has been highlighted whenever data are available. we searched pubmed for original and review articles in english published, using the following keywords: diabetes and infection, hyperglycemia covid- , tuberculosis, vaccination, infections, and diabetes in india, from till september, . the relationship between diabetes and infection has been known for long and has been traditionally considered as bidirectional ( fig. ) ( ). uncontrolled diabetes affects almost all components of immunity: . dysregulated innate immunity including defective neutrophil and macrophage function ( ) . abnormal complement function, which may be related in part to defects in neutrophil function and cytokine responses ( ) . defects in t-cell responses ( ) . defective humoral (antibody-mediated) immunity ( ) in addition, the widespread vasculopathy typical of longstanding uncontrolled diabetes interferes with the body's ability to combat infection by limiting the ingress of immune cells as well as antimicrobial factors, and by promoting tissue necrosis and gangrene. certain features of the hyperglycemic milieu contribute to the growth of specific micro-organisms (e.g. ketosis promoting the growth of fungi causing mucormycosis). the infections met with in diabetes patients can be broadly classified into two categories. . infections that are common in the non-diabetic population, that also affect people with diabetes, often with more severe clinical presentation and worse outcomes. . infections that are peculiar to individuals with diabetes and virtually unknown in the normal population. these include respiratory infections, genitourinary tract infections and skin and soft tissue infections (table ). in a series of patients with diabetes and infections attending a tertiary care centre in north india, the most commonly encountered infections were those of the soft tissues ( . %), respiratory tract ( . %) and genitourinary tract ( . %). infection of more than one site was present in . % of patients ( ) . diabetes has been shown to increase the risk of lower, but not upper respiratory tract infections ( ) . tuberculosis (tb) is a common comorbidity of diabetes, particularly in developing countries. india faces a double burden with the highest number of tb patients, and the second highest number of individuals with diabetes, living within its borders. the relationship between tb and diabetes is bidirectional; individuals with diabetes are more likely to contract tb, and individuals with diabetes are more likely to have diabetes compared to the general population ( ) . the greater risk of contracting tb in diabetes, as well as reactivation of latent tb, is postulated to be due to a combination of susceptibility to infection with oxidative stress and j o u r n a l p r e -p r o o f increased tissue inflammation ( ) . a recent systematic review on the co-prevalence of tb and diabetes in low and middle-income countries found that diabetes was found in . to % of individuals diagnosed with tb, and that . to % of individuals with diabetes had tb ( ) . tb in diabetes has certain peculiar characteristics that make diagnosis and management difficult (see box ) ( ). genitourinary infections found in patients with diabetes include urethritis, vaginitis, cystitis, and prostatitis. common causative organisms are gram negative bacteria such as e. coli and klebsiella and fungi such as candida. in indian patients with diabetes and uti, the most common organisms isolated were e. coli ( . %), klebsiella ( . %) and enterococcus ( . %) ( ) . infection with extended spectrum beta-lactamase producing e. coli was found to be more frequent in individuals with diabetes. also, nearly % of individuals with positive urine culture were found to be asymptomatic. however, current guidelines state that asymptomatic bacteriuria need not be treated, even among patients with diabetes ( ) . use of sodium-glucose cotransporter- inhibitors (sglt i) for management of hyperglycemia has been associated with increased risk of genital mycotic infections ( ); cystitis and upper urinary tract infections are less common but can occasionally occur ( ) . skin and soft tissue infections found in patients with diabetes include furuncles, carbuncles, and cellulitis. in india, more than % of all skin and soft tissue infections have been shown to be associated with staphylococci ( ) . infection is also an important component of the diabetic foot syndrome. most cases of diabetic foot infection have been shown to be polymicrobial in nature, with predominance of gram-negative organisms ( , , ) . prevalence of antimicrobial drug resistance was also found to be higher among patients with diabetes, which could be attributed, at least partially, to the production of biofilms by the causative organisms ( ) . the antimicrobial management of these conditions does not differ significantly from that in the population without diabetes. achievement and maintenance of tight glycemic control, most often requiring the use of intensive insulin therapy, is key to improving outcomes. covid- is an acute, predominantly respiratory viral illness caused by the novel severe acute respiratory syndrome coronavirus (sars-cov ). from studies conducted in china, europe, and the u.s., it appears that individuals with diabetes are not at higher risk of infection with sars-cov compared to the general population ( , ) (box ). however, it is clear that they do tend to have worse outcomes, with respect to development of more severe illness and mortality risk, than individuals without diabetes ( ) . while mortality due to covid- has been lower in south asian countries such as india, the sheer number of individuals with diabetes in this region represents a huge population at high risk of adverse outcomes due to this infection ( , ) . as individuals with diabetes tend to be older and to have higher burden of cardiometabolic risk factors such as obesity and hypertension (as well as cardiovascular disease per se), it is likely that their increased risk of adverse outcomes is mediated, to a large extent, through these comorbidities than by diabetes per se ( ) . recently, there have been reports of new-onset diabetes following infection with sars-cov , mainly from the u.s. ( ) , but increasingly from elsewhere in the world as well. new-onset hyperglycemia during covid infection can have multiple causes-weight gain following disordered diet and exercise during lockdown, mental stress, and unwarranted use of dexamethasone for mild to moderate cases of covid ( ) . it is also likely that the novel sars coronavirus has a direct diabetogenic potential by way of its effects on the pancreas. the angiotensin converting enzyme (ace ) receptor, by means of which sars-cov enters target cells, is also present on the pancreatic beta-cell ( ) . infection of the beta cell may lead to acute impairment of insulin secretion or even destruction of the beta cell, as has been reported for human herpesvirus infection in africa ( ). in individuals with pre-existing diabetes, the current covid pandemic and the public health/ governmental responses to it are also likely to impact glycemic control in significant ways. lack of accessibility to testing and care during lockdowns, increased snacking and reduced physical activity are likely to worsen diabetes control, and predispose patients to complications ( ) , although such deterioration has not been found in all studies ( ) . • a high index of suspicion is required for the diagnosis of most of these conditions. treatment involves, in addition to specific antimicrobial agents, early and aggressive surgical intervention wherever indicated. the prognosis for many of these conditions is poor, even with prompt treatment. while the deleterious effects of uncontrolled hyperglycemia on infection have been well characterized, there is less information available on whether controlling hyperglycemia can have beneficial effects on infection prevention and control ( ) . analysis of patients with type and type diabetes enrolled in primary care in england have shown a clear increase in long-term risk of infection with increasing hba c ( ) . in a population-based study from denmark, individuals with hba c of . % and above had j o u r n a l p r e -p r o o f hazards ratio of . for infections requiring hospitalisation, compared to individuals with hba c between . and . % ( ) . b. hyperglycemia and morbidity and mortality due to covid : during the ongoing covid pandemic, attempts have been made to link the severity of disease outcomes in covid- with the levels of background glycemic control, as well as the glucose levels at admission and during the course of hospitalization. higher hba c at hospitalization, indicating poor long-term glycemic control, has been associated with higher risk of inhospital death due to covid, although this has not been replicated in all studies ( ) . patients with higher blood glucose levels at admission tended to have the most florid lesions on chest imaging and were more likely to require icu admission and intubation and to die compared to those who had lower blood glucose levels ( ) . in-hospital hyperglycemia was associated with worse clinical outcomes among patients with covid studied in china and the u.s ( , ) . these findings reinforce the need for ensuring tight glycemic control in patients with diabetes during the current pandemic, and also for the maintenance of euglycemia in patients who are hospitalized for covid- . in this context, it should be remembered that some medications used for the treatment of severe covid (particularly corticosteroids) have the potential to raise blood glucose levels, and that the antidiabetic drug regimen will need to be appropriately titrated in patients receiving these treatments ( ) . even in the absence of these treatments, infection with sars-cov has been associated with extremely high insulin requirements among patients with diabetes, and the development of hyperglycemic crises in some cases ( ) . the presence of diabetes is associated with increased risk of treatment failure, relapse, and death in patients with tb ( ); similar results have been reported from india as well ( ) . the role of tight glycemic control in improving treatment outcomes in tb remains controversial ( ) . a study from china showed that treatment outcomes were worse among those with suboptimal glycemic control ( ) . similarly, mahishale et al ( ) showed that optimal glycemic control resulted in % reduction of sputum non-conversion at months of treatment compared to poor glycemic control. however, nandakumar et al ( ) found no correlation between diabetes control and tb treatment outcomes in their study conducted in malappuram district of kerala. in this context, it is interesting to note that recent studies have shown an association of poorly controlled diabetes with better outcomes in individuals with low body-mass index; this needs confirmation in larger studies ( ) . maintenance of tight glycemic control during the peri-and postoperative period has been found to be associated with a lower incidence of surgical site infections in patients with diabetes ( , ) . even though maintenance of tight glycemic control has been long considered one of the cornerstones of diabetic foot management, there is little evidence by way of randomized controlled trials to suggest that foot ulcer outcomes are improved by this approach ( ) ; such trials are urgently needed, considering the global magnitude of the problem of diabetic foot. in a retrospective study of more than patients with covid- from china, well controlled blood glucose (defined as glycemic variability between . to mmol/l) was associated with significantly lower mortality compared to higher blood glucose variability (> mmol/l) ( ) . the role of diet has often been overlooked while managing infections in patients with diabetes. some general points can be summarized from available studies: a. severe infection is a hypercatabolic state and any diet plan for patients with infection should take this into account, ensuring adequate intake of protein and micronutrients to promote healing. this is particularly relevant in the indian context, where the baseline protein intake is extremely low. particularly in patients with diabetes and tb without hepatic or renal insufficiency, it is recommended that proteins should be the major source of energy ( ) . b. supplementation of micronutrients for months has been shown to reduce the incidence of common infections (respiratory, skin, and urogenital) in patients with diabetes ( ) . a recent review ( ) on the role of micronutrient supplementation in diabetic foot ulcers concluded that while there was some evidence to support the role of vitamins a, c, d and e, and zinc in ulcer healing, the level of evidence was not strong enough to support any recommendations for routine supplementation with these nutrients. in patients with risk of limb ischemia and/or hypoalbuminemia, supplementation with arginine, glutamine and betahydroxy methyl butyrate has been shown to improve foot ulcer healing ( ) . c. supplementation of vitamin d has been shown to improve the proportion of sputum smear and culture conversion in patients with active pulmonary tb (with or without diabetes) ( ). d. similarly, vitamin d deficiency was associated with an increased risk of testing positive for covid- , raising the possibility that supplementation of this vitamin could reduce the risk of covid infection; however, it should be noted that this study was not restricted to individuals with diabetes ( ). recently, consensus guidelines have been published for balanced nutrition in the time of the covid pandemic ( ) . these can be summarized as follows. a. individuals not infected with covid, or those with mild to moderate disease, consume a balanced diet rich in vegetables, fruit, legumes, nuts, and whole grain as well as egg and lean meat wherever applicable. b. intake of probiotic-rich food is encouraged, and hydration should be maintained particularly when febrile. c. saturated fat and processed food should be avoided, as should extreme "fad" diets. d. the diet should provide at least g of protein per kg body weight per day in older persons and should contain adequate amounts of micronutrients such as vitamins a, c, and d, zinc, and selenium. e. in severely ill patients, these nutritional requirements should be met by way of oral supplementation wherever possible, with enteral and parenteral supplementation being reserved for the most severely ill individuals who cannot tolerate oral intake. as individuals with diabetes represent a vulnerable subgroup of the population with respect to susceptibility to infection, preventing these infections by means of vaccination assumes j o u r n a l p r e -p r o o f paramount importance. in addition to all routine immunisations recommended for the general population, the american diabetes association provides additional recommendations for the use of pneumococcal, influenza and hepatitis b vaccines in individuals with diabetes ( ) . attempts have been made to formulate similar recommendations for india also ( , ) ( table ) . in this context, it should also be noted that the nationwide lockdowns imposed in india and other countries to combat the spread of the covid- pandemic have had an adverse impact on the coverage of infection control and immunization programs directed against other communicable disease; these countries should gear up to face a recrudescence of many of these hitherto controlled infections in the near future ( ) . infectious disease continues to take a heavy toll of the population with diabetes even in the present day. the increased susceptibility of the individual with diabetes to infection has recently returned to sharp focus with the advent of the covid- pandemic, reiterating the need for achieving tight control of hyperglycemia and managing comorbidities appropriately j o u r n a l p r e -p r o o f in this population from the time of diagnosis of diabetes. also, there are certain unusual infections that appear to be exclusively found in patients with diabetes; the clinician dealing with patients with diabetes should be ever alert to the possibility of these infections, as prompt diagnosis may mean the difference between life and death in many cases. j o u r n a l p r e -p r o o f magnitude of the problem: • million people with diabetes worldwide ( million in india) • million infections with covid worldwide as of september ( . million in india) • diabetes per se not a risk factor for contracting covid infection • severe disease and adverse outcomes more likely in individuals with diabetes • poor outcomes may be linked to other comorbidities such as older age, obesity and hypertension, more frequent among people with diabetes • poor long-term (pre-infection) diabetes control, admission hyperglycemia and inpatient hyperglycemia linked with poor outcomes • covid infection can worsen diabetes control • new onset diabetes has been reported with covid mention ketoacidosis • some treatments used for covid treatment (e.g. steroids) can exacerbate hyperglycemia • adverse effect of pandemic and consequent lockdowns on routine diabetes care. this is likely to exacerbate diabetes control and also add new patients of diabetes to already high numbers. • patients unable to exercise regularly, access healthy diet and procure medications promptly. this will increase morbidity and even mortality. j o u r n a l p r e -p r o o f infections in patients with diabetes mellitus: a review of pathogenesis common infections in diabetes: pathogenesis, management and relationship to glycaemic control the role of diabetes mellitus in patients with bloodstream infections immune dysfunction in patients with diabetes mellitus (dm) type diabeets and its impact on the immune system pattern of infections in patients with diabetes mellitus--data from a tertiary care medical center in indian subcontinent increased risk of common infections in patients with type and type diabetes mellitus diabetes and tuberculosis: an important relationship coprevalence of type diabetes mellitus and tuberculosis in low-income and middleincome countries: a systematic review diabetes and tuberculosis: an appraisal clinical profile of urinary tract infections in diabetics and non-diabetics clinical practice guideline for the management of asymptomatic bacteriuria: update by the infectious diseases society of america genital infections with sodium glucose cotransporter- inhibitors: occurrence and management in patients with type diabetes mellitus case of acute unilateral emphysematous pyelonephritis and bacteraemia on treatment with canagliflozin epidemiology of diabetic foot infections in a reference tertiary hospital in india bacterial etiology of diabetic foot infections in south india microbiological and clinical characteristics of diabetic foot infections in northern india infections and diabetes prevalence and impact of cardiovascular metabolic diseases on covid- in china prevalence and impact of diabetes among people infected with sars-cov- covid- in people with diabetes: understanding the reasons for worse outcomes covid in south asians/asian indians: heterogeneity of data and implications for pathophysiology and research covid- in people living with diabetes: an international consensus clinical characteristics and risk factors for mortality of covid- patients with diabetes in wuhan, china: a two-center, retrospective study new-onset diabetes in covid- national diabetes obesity and cholesterol foundation (ndoc), and diabetes expert group, india. strict glycemic control is needed in times of covid epidemic in india: a call for action for all physicians novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure ketosis-prone type diabetes mellitus and human herpesvirus infection in sub-saharan africans increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis acceptability and utilization of newer technologies and effects on glycemic control in type diabetes: lessons learnt from lockdown diabetes and infection: assessing the association with glycaemic control in population-based studies glycemic control and risk of infections among people with type or type diabetes in a large primary care cohort study impact of glycemic control on risk of infections in patients with type diabetes: a population-based cohort study factors associated with covid- -related hospital death in the linked electronic health records of million adult nhs patients admission hyperglycemia and radiological findings of sars-cov in patients with and without diabetes clinical characteristics of patients with diabetes and covid- in wuhan, china glycemic characteristics and clinical outcomes of covid- patients hospitalized in the united states guidance on the management of diabetic ketoacidosis in the exceptional circumstances of the covid- pandemic the impact of diabetes on tuberculosis treatment outcomes: a systematic review effect of diabetes on treatment outcome of smear-positive pulmonary tuberculosis--a report from south india effect of glycemic control and type of diabetes treatment on unsuccessful tb treatment outcomes among people with tb-diabetes: a systematic review the influence of diabetes, glycemic control, and diabetesrelated comorbidities on pulmonary tuberculosis effect of poor glycemic control in newly diagnosed patients with smear-positive pulmonary tuberculosis and type- diabetes mellitus outcome of tuberculosis treatment in patients with diabetes mellitus treated in the revised national tuberculosis control programme in malappuram district impact of diabetes and low body mass index on tuberculosis treatment outcomes postoperative tight glycemic control significantly reduces postoperative infection rates in patients undergoing surgery: a meta-analysis long-term glycemic control and postoperative infectious complications does improving glycemic control accelerate healing of diabetis foot ulcers? association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes insights on medical nutrition therapy for type diabetes mellitus: an indian perspective micronutrients decrease incidence of common infections in type diabetic outpatients micronutrients and natural compounds status and their effects on wound healing in the diabetic foot ulcer effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial effects of vitamin d supplementation on the outcomes of patients with pulmonary tuberculosis: a systematic review and meta-analysis association of vitamin d status and other clinical characteristics with covid- test results balanced nutrition is needed in times of covid epidemic in india: a call for action for all nutritionists and physicians comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes suggested use of vaccines in diabetes rssdi-esi clinical practice recommendations for the management of type diabetes mellitus covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india j o u r n a l p r e -p r o o f • diabetes confers increased risk of common and uncommon infections.• individuals with diabetes have worse outcomes with covid- .• there is a bidirectional link between tuberculosis and diabetes.• good glycemic control improves outcomes in most infections. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: key: cord- -l hfmmbc authors: chowdhury, subhankar; goswami, soumik title: covid- and type diabetes: dealing with the difficult duo date: - - journal: int j diabetes dev ctries doi: . /s - - -z sha: doc_id: cord_uid: l hfmmbc background: coronavirus disease (covid- ) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. the bulk of the evolving evidence in diabetes and covid- relates to type diabetes (t d). since there are a significant number of patients with type diabetes (t d) with unique concerns and challenges during the ongoing covid- pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. methods: we systematically searched the pubmed database up to may , , and retrieved all the articles published on t d and covid- . results: we found relevant articles, each of which carried a part of the evidence regarding the risk of contracting covid- in patients with t d, effect of covid- on development of t d, outcomes in t d with covid- , and special management issues in t d in the light of covid- . these have been documented in the present review. conclusion: covid- with t d presents special challenges. while the available evidence does shed some light, we need more evidence to deal with this difficult duo. coronavirus disease (covid- ) epidemic caused by severe acute respiratory syndrome coronavirus (sars-cov- ) emerged in wuhan, china, in december and has progressed rapidly into a pandemic since the first quarter of [ ] . covid- is commonly characterised by fever, cough, fatigue, shortness of breath, pneumonia, and other respiratory tract symptoms and may even progress to death in some [ ] . patients with older age, hypertension, male gender, heart disease, cerebrovascular disease, kidney disease, hyperglycemia, or history of smoking have been shown to have a higher risk of developing more severe disease and subsequent mortality [ ] [ ] [ ] [ ] . there have been several publications from the global scientific community on covid-! in type diabetes (t d) but markedly fewer looking at type diabetes (t d). t d constitutes about % of all diagnosed cases of diabetes and its global incidence is increasing at about % every year [ ] . given the global burden of t d and unique challenges in treating t d (more so in developing nations like india), this narrative review attempts to address key questions regarding covid- and t d. we systematically searched the pubmed database up to may , , and retrieved articles published on t d and covid- besides looking at relevant websites and related guidelines to form this review. diabetes patients have an increased risk of infection compared with the general population and the risk is even greater in those with t d than in t d [ ] . these include bacterial, viral, and fungal infections of the respiratory tract, urinary tract, gastrointestinal system (including liver), skin and soft tissue, head and neck, and other systemic infections (e.g. hiv) [ ] . this increased risk of infection is due to hyperglycemiainduced immune dysfunction (damage to the neutrophil function, depression of the antioxidant system, and humoral immunity), micro-and macro-angiopathies, and greater requirement of medical interventions in these patients [ ] . interestingly, in reports from italy and china, covid- cases with type diabetes were apparently not reported despite a large number of people being infected and hospitalised [ ] [ ] [ ] . possible explanations for the same include a younger age of t d patients, lower prevalence of t d, and overexpression of cd + t lymphocytes in t d which might play a protective role (cd + t lymphocytes show an increased apoptosis leading to lymphocytopenia in sars-cov infection) [ ] . however, population cohort studies covering all individuals registered with a general practice in england show that t d patients do contract covid- infection requiring hospitalisation in some [ , ] . presently, as testing for covid- is still limited and as there could be many asymptomatic individuals with the infection, it remains unclear whether t dm patients are more likely or less likely to contract covid- . a study in regions with a high prevalence of t d (e.g. scandinavian region) looking at the prevalence of covid- infection with widespread community screening in those with and without t d could possibly provide an answer. since it is well established that uncontrolled hyperglycemia impairs immune function in all forms of diabetes, it would be logical to presume that t d, particularly if not well controlled, could have an increased risk of infection and intensifying glycemic control could serve as a means of primary prevention [ , ] . viral infections are well known to be associated with the development of pancreatic autoantibodies leading to t d in genetically predisposed individuals and coronaviruses were identified as one of the incriminating pathogens in the teddy study [ , ] . viral infections trigger autoimmune insulitis and pancreatic β-cell destruction through several mechanisms-virus amplification cycle and/or circulating viral antigens may directly damage β-cells and also lead to the release of sequestered islet antigens which are presented by overexpressed major histocompatibility complex class i proteins to the immune system, increasing the risk of autoantibody generation. viral epitopes sharing homology to autoantigens could lead to cross-reactive antibody production against β-cells (molecular mimicry hypothesis). also, viral infection leads to cytokine release and t cell activation which could hasten the development of t d in genetically predisposed individuals [ ] . sars-cov- might also bind to ace in the pancreas and cause pancreatic injury, particularly in severe covid- cases, thereby hastening the development of overt t d in susceptible individuals [ ] . as t d development has already been related to coronavirus respiratory infections, it is very likely that an increasing incidence of t dm may be triggered by the present pandemic and appropriately designed studies are necessary in this regard. till such published evidence becomes available, practitioners have to be on an active lookout for the development of t d after covid- in predisposed individuals. there is a report of an individual presenting with diabetic ketoacidosis (dka) as an inaugural feature of t d where dka symptoms were masked by covid- symptoms; this is an area where we need to be vigilant as well [ ] . while t d and its associated comorbidities have established themselves as risk factors for increased hospitalisation, requirement of intensive care, and mortality with covid- , early anecdotal reports from global infection hotspots suggested that children with diabetes had a similar disease pattern compared with children without diabetes (less severe manifestations than adults) [ , ] . on the contrary, a large population cohort study assessing the risk of in-hospital death for individuals registered with a general practice in england showed that people with t d had • ( • - • ) odds of dying in hospital with covid- compared with those without diabetes which was attenuated to • when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease, or heart failure [ ] . however, this study also found a very low absolute risk of in-hospital death for people with diabetes under years of age implying that age was a stronger risk influencer than diabetes status [ ] . another study from england using national diabetes and mortality data showed that the adjusted hazard ratio (hr) for mortality in covid-! with t d of hba c > % compared with hba c . - % was · [ ] . this study also found a ushaped relationship between body mass index (bmi) and covid- mortality with hrs for bmi > kg/m compared with - . kg/m being · ( · - · ) for t d [ ] . evidence from these studies coupled with the fact that glycosylation of ace receptors (which is necessary for cell entry of sars-cov ) can be boosted by hyperglycemia makes a strong case for intensifying glycemic control for improving outcomes in t d with covid- [ ] . a. effect of chloroquine and hydroxychloroquine: there has been an increase in the use of chloroquine and hydroxychloroquine, both for the prophylaxis and treatment of covid- . both these agents have been reported to cause hypoglycemia in patients with and without diabetes (even in those not on insulin or sulphonylureas) [ , ] . chloroquine is postulated to reduce blood glucose (bg) levels by stimulating insulin secretion and also by activating akt to stimulate glucose uptake and glycogen synthase [ ] . hydroxychloroquine decreases insulin degradation at the cellular level, increases intracellular insulin accumulation, and stimulates insulin-mediated glucose transport [ ] . there is a published report of an individual with t d on insulin developing hypoglycemia after taking chloroquine prophylaxis while visiting a malaria endemic area following which this patient even maintained euglycemia without insulin for a temporary period [ ] . therefore, patients with t d who are administered chloroquine or hydroxychloroquine need to be monitored closely for hypoglycemia and their insulin doses adjusted as necessary. b. effect of "lockdown": many countries across the world have imposed "lockdown" measures with restriction of movement and mandatory quarantine of individuals with or at risk of infection. while these measures have been lifted in certain countries, there is a distinct possibility of re-imposition of these measures if a "second wave" of infection appears. since t d is known to be greatly affected by alterations in daily routine, there are concerns that "lockdown" can worsen glycemic control in t d due to restriction of outdoor physical activity, psychological stress on account of lack of physical interaction with acquaintances, irregular sleep pattern, and intake of less healthy diet [ , ] . however, interestingly, there are several publications which have pointed to the contrary-there was either no deterioration in glycemic control or even improvement in glycemic control in t d during "lockdown", particularly in those who continued exercising and in those who did not go out for work [ ] [ ] [ ] . possible explanations include greater parental control and absence of school-related stress in children and adolescents, eating every meal at home with regular timing and more consistent and precise carbohydrate counting, and reduction of workplace-related stress. besides slowing of daily activities which might have helped in glycemic control, patients' apprehension of worsening of covid outcomes could have contributed to improved compliance with physician advice resulting in good bg control. however, these studies have primarily looked at adolescents using a hybrid closed loop system and adults using continuous glucose monitoring with good glycemic control at baseline because of which these findings might not be generalisable to those with poorer control and/or not having access to these new technological tools. another concern is interruption in the availability of insulin and glucose meter test strips in relatively remote area due to logistic issues associated with the "lockdown". in view of this, patients would be well advised to ensure sufficient stocks of essential medical supplies besides maintaining a regular schedule and staying physically active indoors in the interest of good disease control. patients should be encouraged to pursue in-home physical activity (e.g. bodyweight exercise, jump rope, online lessons) as it can not only help improve glycemic control but also for psychological well-being, since physical activity reduces stress and anxiety and improves mood and sleep quality [ , ] . c. risk of dka: while contracting an illness might increase the risk of development of dka in those with known t d, there are reports of delayed diagnosis of new-onset t d leading to presentation with severe dka [ ] . fear of contracting covid- in a hospital setting, reduced access to hospital emergency departments due to travel restrictions, and hospital services remaining closed for non-covid- -related ailments could be some of the causes for this. another reason could be delayed diagnosis on the part of doctors who are preoccupied with covid- and might not consider dka in the differential diagnosis when a patient presents with suspected symptoms either over the telephone or in person. certain features of dka overlap with viral illnesses in children and physicians should be on their toes to look out for polyuria, polydipsia, weight loss, kussmaul's respiration, and a fruity odour in breath. d. prevention of dka: t d patients who are ill should be advised to follow "sick day rules" which are recommended for any stressful situation to reduce the risk of dka [ ] . these include the following: . insulin should never be stopped. . the insulin dose may need to be increased and it might be necessary to take additional doses of rapid acting insulin to bring down the bg levels ( food (rice-lentil broths and sugar-containing fluids) to provide energy and avoid starvation ketosis. . when the child is feeling sick or vomiting and ketone levels are negative or low (trace or small) with bg < - mg/dl, sugar-containing fluids in small amounts (at least ml/h) should be administered to keep bg up. . bg should be maintained between and mg/ dl in otherwise stable individuals. in the following situations, t d patients should promptly get in touch with their treating doctor: when not sure what to do . if they vomit repeatedly (not able to hold down any food or drink for more than h) . if vomiting persists beyond h (particularly in young children) . if bg stays high for more than h . if they develop symptoms which could be indicative of their developing diabetic ketoacidosis (nausea, vomiting, abdominal pain, shortness of breath, confusion). . if blood ketones remain elevated > . mmol/l or urine ketones remain large despite extra insulin and hydration . in very young children (< years) e. management of dka: intravenous (iv) insulin is the standard of care for dka but may pose a challenge in present times as it often requires admission to the intensive care unit (icu). icu beds may be reserved for or be at full capacity with covid- patients besides icu admission leading to an inappropriate risk of infection in young people with t d. in this setting, it may be necessary to manage uncomplicated mild to moderate dka outside the icu setting with subcutaneous (sc) insulin [ ] . sc rapid acting insulin analogs reach peak effect in - min and can be used for the treatment of uncomplicated mild to moderate dka outside the icu setting [ ] . sc regular insulin is an alternative if rapid acting analogs are unavailable. sc rapid acting analogs (lispro/aspart) can be started at a dose of . u/kg h after the commencement of iv fluid replacement. bg levels should be monitored every - h to maintain levels of around mg/dl until dka resolves. sc doses should be injected every h until dka resolution and the dose can be brought down to . u/kg if bg continues to decrease by > mg/dl per hour. however, sc insulin may be unsuitable for those with severe dehydration or serious comorbid conditions. sc regular insulin every h can be used if ph > = at a starting dose of . - . u/kg which can be subsequently increased or decreased stepwise by - % depending on bg values. the dosing frequency can be increased to every h if acidosis does not improve [ , ] . basal insulin should be initiated once dka has resolved and oral intake is tolerated. once dka has resolved and the child is able to drink adequately, the remaining volume of calculated fluid and potassium deficit can be administered orally to facilitate early hospital discharge thereby optimising the use of healthcare resources and also reducing the risk of contracting covid- . intramuscular (im) insulin may be used instead of sc insulin in those with poor tissue perfusion [ ] . in individuals with t d and dka on continuous glucose monitoring system (cgms), confirmatory bg monitoring with finger-prick capillary blood glucose should be performed in view of issues with cgms accuracy in the presence of ketosis and rapidly changing bg levels [ ] . f. psycho-social issues: a questionnaire-based danish cross-sectional study involving adult diabetes patients of whom one-third had t d found that those with t d were more likely to worry about being significantly affected due to diabetes and not being able to manage [ ] . therefore, special attention should be given to those with t d in order to manage their anxieties by providing proper information, counselling, peer support, and access to support helplines. g. use of technology: the covid- pandemic has put the spotlight on telemedicine and brought it to the forefront of diabetes management. telemedicine consultation minimises the risk of virus transmission by maintaining physical distancing thereby alleviating the anxiety of t d patients and their caregivers. it also avoids the cost, time, and inconvenience of travel and waiting at the reception before consultation thereby increasing time for school or work. however, telemedicine does have its share of limitations including inability to perform a proper physical examination, lack of widespread availability of necessary internet-related infrastructure in several developing countries, and difficulty to establish rapport and address behavior modification in patients [ , ] . in settings with access to more advanced technology, remote monitoring of electronic data (cgms, connected insulin pens, connected insulin pumps) enables physicians and other health-care professionals to intervene timely in patients whose condition is deteriorating based on available metrics which could help improve clinical outcomes [ ] . the present covid- pandemic has changed the way we deal with a number of diseases including t d. since we are in the midst of a relatively new and dynamic situation with evolving evidence, we need to be cautious and also rely on logical thinking and common sense to deal with the difficult duo of covid- and t d more effectively. authors' contributions both authors have contributed equally in all aspects. conflicts of interest the authors declare that they have no conflict of interest. early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia for the china medical treatment expert group for covid- risk factors for severity and mortality in adult covid- inpatients in wuhan prevalence and risk factors of mortality among hospitalized patients with covid- : a systematic review and meta-analysis predictors of mortality for patients with covid- pneumonia caused by sars-cov- : a prospective cohort study kidney disease is associated with in-hospital death of patients with covid- incidence and trends of childhood type diabetes worldwide - risk of infection in type and type diabetes compared with the general population: a matched cohort study. cook diabetes care mar infections in patients with diabetes mellitus: a review of pathogenesis covid- lombardy. icu network baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region characteristic of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention prevalence and impact of diabetes among people infected with sars-cov- lack of type diabetes involvement in sars-cov- population: only a particular coincidence? diabetes research and clinical practice -and-diabetes-paper- -full-manuscript.pdf. accessed on th modification of-defensin- by dicarbonyls methylglyoxal and glyoxal inhibits antibacterial and chemotactic function in vitro practical recommendations for the management of diabetes in patients with covid- type diabetes triggered by covid- pandemic: a potential outbreak? respiratory infections are 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diabetic ketoacidosis: low-dose insulin therapy by various routes diabetes and covid- : psychosocial consequences of the covid- pandemic in people with diabetes in denmark-what characterizes people with high levels of covid- -related worries? integrating continuous glucose monitor data directly into the electronic health record: proof of concept managing newonset type diabetes during the covid- pandemic: challenges and opportunities how covid- rapidly transformed clinical practice at the harold schnitzer diabetes health center now and for the future publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -yeucn x authors: altobelli, emma; angeletti, paolo matteo; profeta, valerio f.; petrocelli, reimondo title: lifestyle risk factors for type diabetes mellitus and national diabetes care systems in european countries date: - - journal: nutrients doi: . /nu sha: doc_id: cord_uid: yeucn x background. diabetes is increasing by . % per year in males and . % in females. lifestyle risk factors are related to diabetes. the aim of this work is to highlight within eu- countries the distribution percentages of some lifestyle risk factors and some components of diabetes health care. methods. a literature search was conducted to highlight the presence of diabetes registries, which are fundamental tools for disease surveillance and health planning; the presence of a national diabetes plan (ndp); the care setting; and methods used for reimbursement of drugs, devices, and coverage of any comorbidities associated with diabetes. a multiple correspondence analysis (mca) was carried out to evaluate the possible associations between the variables considered. results. the highest percentages of diabetes (> %) are registered in bulgaria, malta, and hungary. concerning the prevalence of overweight, no european country shows overall percentages of less than %. regarding obesity, % of countries show prevalence rates of %. the record for physical inactivity belongs to malta, with % of individuals being inactive. the percentage of physical inactivity for females is higher than for males across europe. in total, % of the countries have an insurance-based health system, while countries have public national health systems. further, % of countries have an ndp, while % of the eu countries have established a prevalence register for diabetes. conclusions. prevalence rates for type dm in the range of – % are noted in % of eu- countries. in total, out of eu countries show a high prevalence rate for overweight, while % of eu- countries have an obesity prevalence rate of %. diabetes treatment is entrusted to general practitioners in most countries. the results of this work highlight the differences between countries, but also between genders. type diabetes mellitus represents the paradigm of chronic diseases in which there is a close association between family and environmental factors. it is now a health problem with enormous global impact, with estimates of continuous growth [ ] . an important universally recognized risk factor is high calorie intake with limited intake of fiber, which results in an increased accumulation of visceral fat, an increase in body mass index (bmi), and increase in abdominal circumference [ ] . table and figures and summarize the information related to the income and distribution percentages of the following risk factors: overweight, obesity, physical inactivity, and type diabetes. data came from eurostat datasets [ ] and we used the map creator software to build the maps (figures and ) . a literature search was conducted to highlight the presence of diabetes registries as fundamental tools for disease surveillance and health planning ( a literature search was conducted to highlight the presence of diabetes registries as fundamental tools for disease surveillance and health planning ( table ). the keywords used were registries or incidence or prevalence and diabetes mellitus; insulin-dependent registries or incidence or population based and diabetes mellitus, insulin-dependent; "prevalence" or "registries" or "population based" and "diabetes mellitus, type " and "epidemiology"; considering publications from the last years, in english, over years of age. the prisma [ ] method was used to select bibliographic entries ( figure ). only references to type diabetes registries were selected. the data covered the type of health system, presence or absence of a national diabetes plan (ndp), presence of a population-based register, care setting, methods for reimbursement of drugs, devices and coverage of any comorbidities associated with diabetes, and the prevalence of and mortality from diabetes, gathered from the institutional sites of individual european countries to investigate the presence of national data and policies for diabetes control. furthermore, to ensure the completeness of the data, the following sources of information were consulted: eurostat [ ] , who diabetes country profiles [ ] , european commission (ec) [ ], international federation of diabetes (ifd) [ ], foundation of european nurses for diabetes (fend) [ ] , and the world bank [ ] . all data are reported in table . full-text articles excluded, with reasons n = type diabetes registries n= paper without studies included in qualitative synthesis (n = ) (n = eu- countries n = outside eu- countries) the data covered the type of health system, presence or absence of a national diabetes plan (ndp), presence of a population-based register, care setting, methods for reimbursement of drugs, devices and coverage of any comorbidities associated with diabetes, and the prevalence of and mortality from diabetes, gathered from the institutional sites of individual european countries to investigate the presence of national data and policies for diabetes control. furthermore, to ensure the completeness of the data, the following sources of information were consulted: eurostat [ ] , who diabetes country profiles [ ] , european commission (ec) [ ], international federation of diabetes (ifd) [ ], foundation of european nurses for diabetes (fend) [ ] , and the world bank [ ] . all data are reported in table . a multiple correspondence analysis (mca) was carried out in order to to evaluate the possible association between the variables taken into consideration, including eurostat data for the countries of the european union, data relating to mortality per , inhabitants and the mortality trend [ ] , the prevalence of diabetes [ ] , the organization of the health system [ , , ] , the presence of a national diabetes plan, the year of approval [ , ] , the general practitioners and diabetic centers involved, and the cost percentage of diabetes of the total health expenditure [ ] . the variables listed above were classified as follows: percentage of diabetes (≤ %, > %), diabetes mortality (≤ per , , greater than > per , ), mortality trend (growth, stable and in reduction), and percentage cost of diabetes of total health expenditure (≤ %, > %). the mca was conducted using sas statistical software. the graphical representation takes into account the variables that contributed most to the variance. countries belonging to the european union show high income rates, except for bulgaria and romania. the highest percentages of diabetes (> %) are registered in bulgaria, malta, and hungary. values for diabetes of between and % are shown for % of the countries, including the czech republic, croatia, estonia, france, italy, greece, lithuania, latvia, poland, portugal, romania, slovakia, slovenia, and spain; while values between and % are shown for austria, belgium, cyprus, denmark, finland, luxembourg, germany, ireland, sweden, the united kingdom, and the netherlands. regarding men, seven countries ( %) have a diabetes percentage rate higher than %: bulgaria, czech republic, estonia, hungary, malta, spain. regarding women, bulgaria shows a rate of %. concerning overweight individuals, no european country shows overall percentages of less than %. in fact, as many as out of countries ( % of european countries) show a high percentage of overweight of %; the remaining countries show percentages of between and %. overweight affects % of men in countries (czech republic, estonia, luxembourg, malta, spain, and uk) and percentages between - % are shown for states. only latvia has a percentage just below %. the figures for women are globally similar, with the exception of austria, where the percentage of overweight is slightly lower ( . %). in out of countries, the percentage of female overweight is between and %, while in countries the percentage exceeds % (czech republic, denmark, estonia, greece, latvia, lithuania, malta, poland, spain, uk). regarding obesity, % of european countries show values of obesity of %: bulgaria, croatia, czech republic, estonia, france, greece, france, hungary, ireland, latvia, lithuania, malta, poland, slovakia, slovenia, spain, uk). percentages in the range of . - . % are shown for cyprus, italy and romania. the remaining countries show obesity percentages ranging between and %. regarding gender, obesity rates are above % for men in countries (czech republic, estonia, luxemburg, uk), while the lowest values are recorded in austria, portugal, and romania. particularly relevant is that in some countries (czech republic, malta, estonia, and uk) the percentage of obese women is greater than %. instead, the percentage exceeds % in countries (bulgaria, cyprus, france, hungary, ireland, lithuania, poland, slovakia, slovenia, and spain). on the other hand, the percentages of physical inactivity are more variable from country to country. the highest value for physical inactivity belongs to malta with %, followed by countries in southern europe (italy, spain, portugal) and northern europe (belgium and the united kingdom). it is important to underline that the percentage of physical inactivity in females is higher than in males across europe. a total of , references were identified through database searching were, while were identified through manual searching. of these, references were excluded because they were duplicates. of the remaining papers, were selected as potentially valid for the systematic review. nutrients , , of a further papers were excluded for not containing the requested information. in total, papers were analyzed, of which covered type dm and covered type dm (figure prisma flow chart). of the latter , were eu- countries and were from outside the eu- . all results are described in table . european health systems vary from country to country, and even within individual countries. however, in most european countries ( %) there are insurance-based health systems, while in countries there are public national health systems. in % of countries, there are national diabetes plans. in total, % of the countries belonging to the european union have established a prevalence register for diabetes. diabetes care is mainly entrusted to the general practitioner in countries, while in the remaining countries it is entrusted to diabetes centers. in health systems where health care is totally managed by the state government, the latter provides coverage for drugs, devices, and associated comorbidities, except for latvia. in insurance systems, on the other hand, only in belgium is there full coverage for expenses relating to drugs, devices, and comorbidities, while in the remaining countries there are shares for different copayments. mortality is extremely variable; the lowest values are found in finland, while the highest values are present in the islands malta and cyprus. there are only two countries with values above / , , which are croatia and czech republic; while mortality values of between and / . are found in austria, portugal. and hungary. seven out of countries show mortality values of between and , including bulgaria, denmark, germany, italy, latvia, poland, and sweden. in total, % of european countries show mortality values of between and / , , including belgium, estonia, france, greece, ireland, lithuania, luxembourg, romania, slovakia, spain, uk, and the netherlands. the country and year of approval of each national diabetes plan represent the first dimension, which account for about % of the variance; the prevalence and mortality trends represent the second dimensions, which account for around % of the variance. all results are represented in figure . nutrients , , x for peer review of trend, and a health expenditure for diabetes < % of the total national health expenditure. the cloud of points represents the presence of an ndp, health expenditure for diabetes < %, and the presence of the national health service. the chronicity control system is represented by the chronic care model (ccm), which was developed in the mid- s by wagner [ , ] . this model covers the needs of health organizations and citizens. the ccm provides six levels of implementation: the organization of care systems with the removal of barriers; self-management with support from a caregiver; support for decisions on prevention or treatment strategies based on medical evidence; delivery of services; a system for recording and monitoring care and community and public health resources [ ] . for diabetes mellitus, this means a combination of programs the first quadrant includes the following countries and variables-finland, the united kingdom, ireland, sweden, belgium, austria, luxembourg, the netherlands, each showing a mortality rate below . , diabetes < %, stable mortality trend, and with diabetes care entrusted to general practitioners. in this quadrant, a cloud of points can be seen, showing mortality < / , diabetes < % for austria and netherlands, with diabetes care entrusted to general practitioners. the following countries and variables represent the second quadrant-estonia, bulgaria, poland, romania, lithuania, latvia, france, and germany, each showing health expenditure for diabetes > % compared to the total health expenditure, an increasing mortality trend, the absence of a national diabetes plan for diabetes, and health insurance. in this quadrant, an aggregation zone can be highlighted, which includes the absence of a national diabetes plan, a rising mortality trend, and health insurance. hungary, the czech republic, slovenia, greece, croatia, cyprus, malta, and the geographical area of eastern europe represent the third quadrant, each having a mortality rate greater than %, the approval after of the ndp, a % of diabetes > %, and the presence of diabetes services. it is important to underline that a point of clouds includes mortality greater than %, percentage of diabetes > %, and approval year of the ndp after . the fourth quadrant includes portugal, italy, spain, slovak republic, denmark, each showing the presence of a ndp, a ndp approved before , a national health system, a decreasing mortality trend, and a health expenditure for diabetes < % of the total national health expenditure. the cloud of points represents the presence of an ndp, health expenditure for diabetes < %, and the presence of the national health service. the chronicity control system is represented by the chronic care model (ccm), which was developed in the mid- s by wagner [ , ] . this model covers the needs of health organizations and citizens. the ccm provides six levels of implementation: the organization of care systems with the removal of barriers; self-management with support from a caregiver; support for decisions on prevention or treatment strategies based on medical evidence; delivery of services; a system for recording and monitoring care and community and public health resources [ ] . for diabetes mellitus, this means a combination of programs aimed at nutrition education, autonomous control of blood glucose with related strategies, psychological support, and personal empowerment [ ] . the growth estimates for diabetes in europe are quite clear-an increase from . million cases in to . million cases in [ ]. these data are even more alarming in light of the recent sars-cov pandemic, posing a problem to healthcare stakeholders. in fact, diabetics are more susceptible to lower respiratory tract infections due to the abnormal neutrophil function induced by hyperglycemia [ ] . data from clinical studies show the increased susceptibility of diabetics affected by atypical pneumonia [ ] . in this context, the enhancement of telemedicine services appears to be a priority in the control of chronic diseases, especially in lockdown periods. a recent meta-analysis has shown that telemedicine for diabetes treatment is cost effective for both retinal screening and telemonitoring [ ] . another work highlights how the control of the diabetic via telematics allows better control of glycated hemoglobin [ ] , which is the main marker of diabetes progression [ ] . an important aspect to consider is the organization of diabetes services. the economic crisis of the period - severely tested the health systems of individual countries, with progressive cuts to some services or increases in copayment quotas. some health systems, by virtue of their organization or recent reform, have been able to cope with these new economic scenarios, while others have found themselves in more difficulty; the effects of the recent economic crisis are still fully visible in terms of mortality trends [ ] . the close associations between the organizational and financial aspects can be deduced from the distribution of the variables obtained from the analysis of the reports. in fact, it is clear that the activation of a national diabetes plan can contribute to the reduction of the prevalence of mortality from dm and the containment of the global costs of diabetes. our results show that in countries where there is a national health system (uk, italy, spain, portugal) or an insurance system with high social protection (the netherlands, france), excellent performance is noted in the control of diabetic disease and its comorbidities. in fact, the guarantee of access to therapies and control and prevention of complications contribute to reducing mortality, while at the same time lead to significant savings. these results are most evident in countries where a national diabetes control plan has been in place for at least years. another aspect that emerges from our analysis is the care setting. in fact, it seems that the management of diabetes by practitioners compared to diabetic centers guarantees better results in terms of the prevalence of and mortality from t dm, as underlined by the aforementioned meta-analysis of gupta et al. [ ] . access to care or better delivery of care represents one of the cornerstones of the ccm model. in our opinion, a similar system should also cover obese individuals by actively involving them in prevention policies, emphasizing self-care by self-management [ ] . our data show that obesity and being overweight are closely related to physical inactivity, especially in females, representing a gender gap. an emphasis on this theme was noted for the women's football world championship [ ] . countries should make greater efforts to guarantee women access to sports activities, promoting the removal of sociocultural barriers and with ad hoc investments; for example, it has been shown that quality public transport and travel infrastructure for pedestrians could reduce the gender gap, allowing women to practice physical activity with greater ease and accessibility [ ] . this is a fundamental aspect, especially in light of the fact that physical inactivity is one of the determinants of non-communicable diseases [ ] and one of the main determinants of the increase in bmi, and therefore of obesity [ ] . in fact, it has been estimated that by , in eu- countries obesity will reduce life expectancy rates from . to . years and that . % of health budgets will be used to treat complications associated with obesity. moreover, the consequent economic effects of obesity directly reduce productive activities [ , ] . in conclusion, % of eu countries show type dm prevalence rates in the range of - %. in addition, of the eu- countries show a high percentage of overweight, while % of eu- countries have an obesity prevalence rate of %. the record for physical inactivity belongs to malta. in general, physical inactivity rates are higher for females than males. regarding care organizations, national public insurance is present in % of countries. diabetes treatment is entrusted to general practitioners in most countries. the results of this work highlight the differences between countries, but also between genders. the patterns identified could indicate cultural and gender trends to which future public health interventions should be addressed. greater attention should be given to the fight against risk factors for non-communicable diseases, particularly diabetes, considering its high prevalence. this must be a priority for citizens at higher risk. the authors declare no conflict of interest. the founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. international diabetes federation: brussels ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism environmental/lifestyle factors in the pathogenesis and prevention of type diabetes variation and trends in incidence of childhood diabetes in europe genetic and environmental factors affect the 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prisma statement death due to diabetes mellitus, by sex who. diabetes country profiles. available online diabetes in europe policy puzzle: the state we are in. int. diabetes nurs country and lending groups global healthcare expenditure on diabetes for and organizing care for patients with chronic illness organizing care for patients with chronic illness revisited effectiveness of chronic care models for the management of type diabetes mellitus in europe: a systematic review and meta-analysis joint action on chronic diseases and promoting healthy ageing across the life cycle (ja-chrodis). health promotion interventions in type diabetes covid- infection in italian people with diabetes: lessons learned for our future (an experience to be used) diabetes and infection: is there a link?-a mini-review telemedicine cost-effectiveness for diabetes management: a systematic review does telemedicine improve treatment outcomes for diabetes? a meta-analysis of results from randomized controlled trials action to control cardiovascular risk in diabete study group effects di intensive glucose bassaering in type diabetes financial crisis, austerity, and health in europe foucault at the bedside: a critical analysis of empowering a healthy lifestyle time to tackle the physical activity gender gap large-scale physical activity data reveal worldwide activity inequality the role of obesity and lifestyle behaviours in a productive workforce the heavy burden of obesity: the economics of prevention, oecd health policy studies key: cord- -gmlsoo z authors: avilés-santa, m. larissa; monroig-rivera, alberto; soto-soto, alvin; lindberg, nangel m. title: current state of diabetes mellitus prevalence, awareness, treatment, and control in latin america: challenges and innovative solutions to improve health outcomes across the continent date: - - journal: curr diab rep doi: . /s - - - sha: doc_id: cord_uid: gmlsoo z purpose of review: latin america is the scenario of great inequalities where about million human beings live with diabetes. through this review, we aimed at describing the current state of the prevalence, awareness, treatment, and control of diabetes mellitus and completion of selected guidelines of care across latin america and identify opportunities to advance research that promotes better health outcomes. recent findings: the prevalence of diabetes mellitus has been consistently increasing across the region, with some variation: higher prevalence in mexico, haiti, and puerto rico and lower in colombia, ecuador, dominican republic, peru, and uruguay. prevalence assessment methods vary, and potentially underestimating the real number of persons with diabetes. diabetes unawareness varies widely, with up to % of persons with diabetes who do not know they may have the disease. glycemic, blood pressure, and ldl-c control and completion of guidelines to prevent microvascular complications are not consistently assessed across studies, and the achievement of control goals is suboptimal. on the other hand, multiple interventions, point-of-care/rapid assessment tools, and alternative models of health care delivery have been proposed and tested throughout latin america. summary: the prevalence of diabetes mellitus continues to rise across latin america, and the number of those with the disease may be underestimated. however, some local governments are embedding more comprehensive diabetes assessments in their local national surveys. clinicians and public health advocates in the region have proposed and initiated various multi-level interventions to address this enormous challenge in the region. within the last couple of decades, non-communicable diseases (ncds) have gained worldwide attention, especially in low-and middle-income countries (lmic), where they have been increasingly recognized and prevalent [ , ] . among the ncds, diabetes mellitus has become a global health challenge [ , , ] . type diabetes mellitus-the most common form of diabetes-due to its rather silent disruption may be a current uninvited companion to over million persons worldwide. in , it was estimated that the number of persons with diabetes in latin america (latam) was . million [ , ] and is predicted that by , the number will increase to . million, and to . million by [ ] . because of its multi-organ and multi-system impact, diabetes has been associated with both acute and long-term complications that affect not only health care needs and costs but also wellbeing and productivity [ , ] . within the last decade, it has also been recognized as one of the leading causes of death in some latam countries [ ] [ ] [ ] [ ] [ ] [ ] [ ] and an important risk factor this article is part of the topical collection on diabetes epidemiology for cardiovascular diseases (cvd), which is the leading cause of death in latam [ , ] . far from being a monolithic group, the latam population is highly heterogeneous, with various populations reflecting diverse genetic ancestry, ethnicity, culture of origin, sociopolitical contexts, environmental exposures, and beliefs and practices [ , ] . levels of inequality in latam remain among the highest in the world [ ] [ ] [ ] [ ] . all these factorscoupled with biological susceptibility, income, education, access health care, cultural influences on nutrition, health, selfimage, and self-care-influence the development of diabetes in latam. we conducted a review of the most current publications on the state of prevalence, awareness, treatment, and control of diabetes mellitus across latam. by laying out a detailed accounting of what is known, we aim to identify population, clinical, and health care needs, and opportunities for future research studies and potential interventions. we conducted the search using the pubmed electronic database as the primary scientific literature source. latam was defined as the countries in the western hemisphere which were previously colonized by spain, portugal, or france. a combination of keywords was used to define the scope of the searches: diabetes prevalence, awareness, treatment, control, guidelines of care, adherence, retinopathy, nephropathy, neuropathy, foot care, fundoscopic exam, and urine albumin, and searched under latam and by each individual country. hispanics/latinos living in the usa were not included in the search. we limited the search to publications since to reflect the most recent research on the prevalence of diabetes across latam countries, assessments of awareness, treatment, and control of diabetes (glycemic control), blood pressure and low-density lipoprotein cholesterol (ldl-c), and adherence to guidelines for care recommended by the american diabetes association (ada) [ ] [ ] [ ] and the latin american diabetes association (alad) [ ] , and specifically hemoglobin a c (hba c) measurement, fundoscopic exam, foot exam, and urine albumin excretion test. we included literature written in english, spanish, french, and portuguese. in addition to pubmed, when available, we manually searched each country's ministry of health and the pan american health organization (paho) websites and accessed published and downloadable national health surveys performed during the selected timeframe. since most available studies did not distinguish between type and type diabetes mellitus, our review is centered on diabetes mellitus (diabetes, henceforth) in general. because their specific mechanisms of disease and clinical implications, gestational diabetes mellitus, and type diabetes merit separate reviews. the earliest contemporary reports on the prevalence of diabetes mellitus among adults throughout latam date from the s and s [ ] [ ] [ ] , when most countries were beginning to experience epidemiologic transitions [ , ] . in , barceló reported an incidence of type diabetes in latam in the range . cases/ , in venezuela to . cases/ , in puerto rico [ ] . however, the authors highlighted a handful of reports on the prevalence of type diabetes and underlined the near absence of surveillance for the disease throughout the latam region [ ] . from to , the prevalence of diabetes mellitus across latam has been assessed within individual countries and through multinational studies and ranged between and . % (fig. , table ). in our review, some national surveys assessed the prevalence of diabetes via population representative samples [ , , , , - , , , , , , , , , , - , , , , , , ] and used similar population sampling methods (e.g., multi-stage, clustered, probabilistic sampling), whereas other studies focused on specific geographic regions or communities [ , , , , , - , - , , , - , , - , - , , - ] , recruited participants from clinical settings [ , , , , ] , or focused on specific age groups [ , , - , , , ] . also, the age range of the population surveyed-and consequently, age-adjustment estimates-varied among surveys. most of the studies (especially national surveys) reported the overall prevalence of diabetes without differentiating between type and type diabetes mellitus and many estimated the prevalence of the disease based on selfreport (being aware of having diabetes and/or taking antihyperglycemic medications) only. some national surveys and independent studies estimated the prevalence based on the sum of self-report and identifying individuals without history of diabetes but hyperglycemia within the diabetes range [ , ] . the latter group was considered to have "suspected," "undiagnosed," or "unknown" diabetes. hyperglycemia within the diabetes range was assessed by measuring fasting blood or plasma glucose (fbg or fpg) only, fbg/fpg and -h oral glucose tolerance test (ogtt), fbg/fpg and hemoglobin a c (hba c), hba c only, or the combination of fbg/fpg, ogtt, and hba c, or glucose levels in urine. some studies measured capillary blood glucose (cbg), while most studies measured venous blood or plasma glucose. while multiple studies used the ada/alad-recommended glucose/hba c cut points for the diagnosis of diabetes [ , ] , some studies used different thresholds (e.g., fasting glucose ≥ mg/dl (per cbg), random blood glucose ≥ mg/dl, or random blood glucose ≥ mg/dl). although the differences in the methodology described above limit the ability to perform cross-sectional or trend comparisons among countries, we note several commonalities. during - , some countries reported an increase in the prevalence of diabetes [ , , - , , - , , , ] , consistent with previously published reviews [ , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . compared with the rest of the region, and as previously reported [ , , , , ] , diabetes prevalence varies across the region, with higher prevalence in mexico ( . %), haiti ( . % in women and . % in men), and puerto rico ( . - . % in the population aged ≥ years and . % in the population aged ≥ years), and lower in colombia ( . % in the population aged ≥ years, but . % in age group ≥ years), dominican republic ( . %), ecuador ( . %), peru ( . %), and uruguay ( . - . %) (fig. , table ). multiple studies reported a greater prevalence of diabetes among women [ , , , , , , - , , , , , , , , , , , - , , , , , ] , and with increasing age, especially over age years [ , , , , , , - , , , , , , , ] . some studies reported an inverse relationship between diabetes and socioeconomic status (ses) [ , , ] or educational attainment [ , , , , , , , , , , , , ] . other studies reported a direct relationship between having health insurance and self-reported diabetes [ , , , ] , implying that persons who have health insurance-proxy of access to health care services-would be aware of their health issues and report them accordingly. this interaction also poses questions about not only the access to health care but also the timeliness and quality of the care, and health literacy (or the lack of) that persons in the lowest ses-and at the highest risk of diabetes-would experience. some studies reported a lower prevalence of diabetes among indigenous populations [ , , ] , with one study proposing that exposure to urbanicity was associated with an increased prevalence of diabetes among some indigenous communities [ ] . indeed, rural to urban migration (or living in rural compared with urban areas) has been associated with increased prevalence or risk of developing diabetes in peru [ , ] , and multiple countries reported a lower diabetes prevalence in rural compared with urban settings [ , , , , , - , , ] . the number of epidemiological studies published since indicates greater public health awareness about diabetes mellitus across latam. multiple countries have performed at least one national survey on chronic non-communicable diseases in which self-reported diabetes mellitus and/or elevated glycemia has been included (table ) . some surveys have also included at least one laboratory test (i.e., fasting or random blood glucose measurement or hba c), which could identify individuals at risk of developing diabetes or those who may have it and are not aware of it. because hyperglycemia may be mediated by at least two mechanisms of disease-increased hepatic glucose output manifested as fasting hyperglycemia and uncoupled postprandial insulin secretion manifested as postprandial hyperglycemia [ , ] -a single blood test or measurement may not identify all or most of individuals affected by the disease [ ] . therefore, the actual prevalence of diabetes may still be underestimated in many countries, as highlighted in previous reviews [ , , ] . the etiologies of diabetes mellitus are complex. thus, the increasing prevalence of diabetes experienced across latam may reflect the convergence or interaction of multiple factors [ , , ] . for instance, the increasing prevalence of overweight and obesity documented across latam has paralleled the increasing prevalence of diabetes in the region [ , , , ] . in addition to increased adiposity, type diabetes mellitus and insulin resistance have also been linked to malnutrition (at different life stages) in some lmics [ , [ ] [ ] [ ] . stress associated with chronic poverty, intergenerational poverty, natural disasters, and other adverse events [ , , , ] has been linked to chronic systemic inflammation and epigenetic changes, potential common denominators of multiple ncds [ , ] . many latam major cities may be epicenters where a fragile built environment and infrastructure and changes in lifestyle and nutrition intersect increasing the cumulative risk of developing diabetes in low-income communities [ , , , , , , ] . increased life expectancy has been associated with increased diabetes prevalence [ , , , , ] , whereas higher educational attainment, increased access to health care, and higher health literacy level are associated with increased awareness of the disease [ ] . these are all factors to consider upon designing comprehensive diabetes prevention and treatment strategies across latam countries. in addition, the growing prevalence of diabetes mellitus across latam and the complexity of the disease suggest opportunities to create or strengthen collaborations towards its prevention and early detection [ ] [ ] [ ] [ ] . for example, multinational and multidisciplinary researchpublic health-health care policy-clinical care partnerships which already exist in formal or informal platforms may be well-positioned to evaluate the impact of nutrition, health insurance, housing, and other public policies [ , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] on health outcomes and assess their potential translation into preventive strategies at the public health and clinical care levels. at the same time, the eventual implementation of such strategies will be strengthened by local governments' commitment to prioritize the prevention and treatment of ncds, in this case, diabetes, as previously voiced by experts and advocates in the region [ , , [ ] [ ] [ ] [ ] . diabetes awareness, treatment, and control although fewer than studies focused on prevalence, a considerable number of reports centered on diabetes awareness, treatment, and control across latam were published between and ( , ] . most studies did not use the term "diabetes awareness," but equated it (or more appropriately, diabetes unawareness) to "suspected," "undiagnosed," "unknown," or "new" diabetes or "elevated glycemia." "undiagnosed" diabetes-a proxy for lack of diabetes awareness-ranged widely from . to % across studies and countries ( table ). the prevalence of undiagnosed diabetes was higher in guatemala ( . %), uruguay ( . %), puerto rico ( . - %), honduras ( . - . % range), mexico ( . - % range), and nicaragua ( . %) and lower in colombia (bogota) ( . %), the southernmost countries of south america ( . %), and costa rica ( . - . %). irazola et al. [ ] described that diabetes awareness slightly increased with educational attainment. however, associations between undiagnosed diabetes with age, sex, educational attainment, ses, or geographic location were not published by most studies. the observed range of undiagnosed diabetes suggests that the actual prevalence of diabetes across latam could exceed previous estimates [ , ] and that a potentially significant proportion of persons with diabetes for whom both macroand microvascular complications may be present but not assessed and treated. therefore, current estimates of the prevalence of diabetes across continents may not fully account for the necessary resources to provide adequate health care for latin americans with diabetes [ , , , ] . considering the workforce and resources needed to screen the millions of persons across the region who are at risk of diabetes or have the disease and are not aware, experts have proposed diabetes predictive models requiring specific easily obtained clinical data points that could be readily used in primary care settings [ ] [ ] [ ] . also, the finnish diabetes risk score (findrisc) has been proposed, tested, or modified to screen and identify individuals at high risk of developing diabetes in latin america [ ] [ ] [ ] [ ] [ ] . point-of-care tests for hba c and urine microalbumin have also been proposed as alternatives to identify persons with "undiagnosed diabetes" and/or those at risk of chronic kidney disease (ckd) in low-resource and remote settings in latam [ ] [ ] [ ] [ ] . the standardization, reliability, and repeatability of some of these tests, as well as the clinical and public health benefit derived from their integration into the health care systems, may need to be determined [ ] . however, these and other emerging diagnostic technologies [ , ] are promising alternatives that could be incorporated to assess the prevalence of diabetes and implement timely interventions. the percent of persons with diabetes following any treatment for diabetes ranged from . to % across studies ( table ). prescription and/or use of antihyperglycemic medications was mostly assessed via interviews, although a few studies evaluated medical records. most individuals reported taking oral antihyperglycemic medications either as monotherapy or as a combination of oral medications, while a smaller percent reported using insulin alone or in combination with oral medications. five ( %) to . % only followed diet/exercise prescription [ , , , , , ] , and . to . % were not taking any medications [ , , , , ] . receiving or adhering to pharmacological treatment was positively associated with having health insurance [ ], and receiving medical care in private rather than public health care settings [ , ] . at least one study observed better pharmacologic treatment adherence with female sex [ ] . achievement of ada/alad-recommended glycemic goals [ , ] was assessed by multiple studies. the percentage of persons attaining hba c < % ranged from . to %. however, some studies defined glycemic control based on fasting or random blood glucose thresholds and reported attainment of glycemic control in the . to . % range. attainment of glycemic control was associated with higher socioeconomic status (ses) [ ] , having health insurance [ ] , and better access and services [ ] . not attaining glycemic control was associated with longer duration of diabetes [ , , ] , taking insulin (alone or in combination with oral antihyperglycemic medications) [ ] , forgetfulness (e.g., taking multiple medication for more than one condition) [ ] , complex therapeutic regimes [ ] , inadequate access to health care services [ ] , and availability or health insurance coverage of medications [ ] , among other factors. in addition to glycemic control, a smaller number of studies examined the attainment of ada/aladrecommended blood pressure and ldl-c-blood pressure < / mmhg and ldl-c < mg/dl-for patients with diabetes [ , ] . the percentage achieving blood pressure goals ranged from to %, and the percent achieving ldl-c goals ranged from to . % table ). the percent achieving optimal glycemic, blood pressure, and ldl-c levels altogether was reported by a handful of studies and up to . % ( table ) . the findings described above denote critical aspects of the state of diabetes care in latin america. the achievement of glycemic goals reported by the studies included in our review is similar to previously published studies [ , , , , ] . this implies seriously chronic and inadequate glycemic control at the population level across the region. the inclusion of questions on treatment for glycemic control, medical, and self-care in some national surveys increases our understanding of health-seeking behaviors, both patients' and clinicians' adherence to recommended guidelines of care, and challenges related to the utilization of health care services and availability of medications. the smaller number of studies reporting on the attainment of blood pressure and ldl-c goals and the proportion of patients achieving those goals also poses questions about the prevention of macrovascular complications in persons with diabetes in latin america, considering the raising prevalence of cvd in the region [ , ] . of note, most national surveys report prevalence and treatment and/or control of diabetes, hypertension, and blood cholesterol and the prevalence of tobacco use individually. since diabetes involves multiple organs and deserves a holistic care approach, reporting on the co-existence of other cv risk factors with diabetes would enhance critical understanding of cv risk and health care needs. also, some surveys collected biospecimens, but the test results were not included in the reports. it is possible that they are analyzed and published later. yet including test results in the surveys would offer a more comprehensive picture of the status of diabetes prevention and care needs [ , , ] to plan interventions accordingly. various studies included in our review reported on participants' receiving or following ada/alad-recommended guidelines of care [ ] for early detection and prevention of microvascular disease-annual fundoscopic exam, examination for peripheral neuropathy and comprehensive foot examination, annual function/urine albumin excretion testing, and hba c tested at least times per years [ - , , , , , , , , , , , , , , , , ] (table ) . some studies assessed the completion of several guidelines, whereas most studies focused on a few. the completion of the selected ada guidelines varied, ranging from . to . % for the foot exam, from . to % for the fundoscopic exam, and from . to . % for the urine albumin excretion test. most studies (especially national surveys) inquired about having hba c checked within the previous months. the affirmative response ranged from . to . %. in addition to inquiring about hba c testing, some surveys asked whether the participant's blood glucose had been tested (by a health care professional). having private health insurance was associated with a greater number of affirmative responses to the latter [ , , ] . despite the smaller number of studies evaluating the completion of the ada guidelines for foot care and prevention of microvascular disease, and the varied guideline completion rates previously described (table ) , the prevalence of long-term microvascular complications associated with diabetes has been documented across latam. for instance, in the studies included on our review and others published during the same time frame, the rate of foot ulcers ranged from . to . % [ , [ ] [ ] [ ] , and nontraumatic lower extremity amputations attributable to diabetes ranges from . to . % [ , , , , [ ] [ ] [ ] [ ] [ ] , and the prevalence of diabetic retinopathy ranged from . to % [ , , , , ] . ckd has become a major public health concern across central america [ ] [ ] [ ] , and the increasing prevalence of diabetes could exacerbate the incidence of ckd-and eventually end-stage renal disease and its associated health complications-in the region [ ] [ ] [ ] . the findings described above underline not just the urgent need to prevent diabetes but also to prevent complications among those with established disease, and the potentially underestimated burden on patients, societies, and health care systems across latam. in this regard, several innovative models of health care for patients with diabetes have been proposed and tested throughout latam. combining care of diabetes and other chronic conditions would be expected to maximize time and resources and improve health outcome. although combining diabetes and chronic pulmonary disease care did not demonstrate a difference in outcomes [ ] , this model could be revisited. also, interventions at the health care system element of the chronic care model might need to be adapted to the local health care system [ ] or synchronized with interventions at other levels. improvement of health care system structure and processes [ ] would assure timely access to patient information and enhance clinician decisionmaking. integrating social determinants of health into diabetes care demonstrated objective improvements in patient knowledge and cardiometabolic parameters [ ] . enhancing medical continuing education [ ] , an intervention combining diabetes prevention and self-management [ ] , co-creating interventions with community stakeholders and other countries [ , ] are other examples of alternatives to improve diabetes care throughout the region. another major regional example of efforts to implement better care for patients with [ ] , telehealth, mobile clinics, and other non-traditional health care delivery models. in addition, a non-exhaustive list of examples of past or current interventions, policies, and initiatives is provided in table [ , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . interventions in the list include tele-ophthalmology [ , , , ] , teambased foot self-care education [ ] , diabetic retinopathy education and screening at a community pharmacy [ ] , rapid assessment/diagnostic tools to screen for or detect retinopathy, nephropathy, and risk of developing foot ulcers [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] and are examples of clinical research and/or implementation activities designed to strengthen the prevention and early detection of diabetes-associated complications and improve health outcomes throughout latam. many interventions on diabetes care have focused on patients and/or clinicians as the primary recipients or enablers of the interventions. because of the complex nature of the disease and the multiple factors that mediate treatment effectiveness, interventions involving other levels or elements within the health care organization or system [ , , , [ ] [ ] [ ] or the health care workforce [ , , ] could be considered. interventions involving other sectors (e.g., housing, infrastructure, national or local policies) could uncover very valuable and needed strategies to enhance treatment effectiveness and potentially reduce health care costs in the long-term. the feasibility and sustainability of such research efforts-and subsequent policies-would need to be demonstrated and supported locally [ ] . multiple studies in our review reported a higher prevalence of diabetes among women [ , , , , , , - , , , , , , , , , , , - , , , , , ] . while the mediating factors for this sex difference need further study (e.g., history of gdm, which was outside of the scope of this review), the increased prevalence of diabetes among women in some latam countries would be expected to have implications for health and health care, and potentially future generations [ ] [ ] [ ] . since diabetes may increase women's risk for cvd, including stroke [ ] , cognitive decline [ , ] , or some cancers [ , ] , timely and comprehensive preventive care for women of all ages would need to be prioritized. due to the epidemiologic transition already experienced by some countries throughout latam, the population pyramid is also shifting towards a greater proportion of older adults. studies included in our review consistently reported an increased prevalence of diabetes with age. diabetes care challenges specific to this age group include risk of obesity or undernutrition [ , ] , increased risk for disability [ ] , economic barriers to appropriate access to health care [ ] , disruption in funding of health insurance [ ] , disparate completion of diabetes care guidelines based on health insurance coverage [ ] , inequalities in access to and utilization of health care services [ ] [ ] [ ] , complex medical care needs and frailty [ ] , cultural beliefs, mental health, and lack of family or social support [ ] , among others. prevention of diabetes and its complications and reliable continuity of care and social support [ ] need to be especially tailored for this population across the region. a few studies in our review reported a low prevalence of diabetes among some indigenous populations in latam [ , , ] , in parallel to some previous reports [ ] [ ] [ ] [ ] about other indigenous groups in the region and in contrast with the higher prevalence of diabetes among american indians in the usa [ ] and the first nations in canada [ ] . however, other studies in our review and in the current literature have documented elevated diabetes prevalence or risk among indigenous and other socioeconomically disadvantaged ethnic groups [ , , , , , , , , , [ ] [ ] [ ] [ ] [ ] . some of the diabetes prevalence studies included in our review focused on or mentioned participants from indigenous groups [ , , , , ] and other underrepresented groups (e.g., garifuna, afro-panamanian, afro-peruvian, afro-ecuadorian) [ , , , , ] . however, a few studies have evaluated diabetes care, prevalence, and/or prevention of macro-or microvascular complications, diabetes management interventions, other health care needs and access to health care among indigenous populations [ , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , and none on the other groups (that we could identify through our search). understanding the protective mechanisms (e.g., biochemical, immune, epigenetic) against diabetes experienced by some indigenous populations would be relevant to millions at high risk of developing diabetes. at the same time, the increased prevalence of the metabolic syndrome and diabetes experienced by some indigenous groups and other ethnic groups may increase their risk not only for cvd and other diabetes long-term complications but also for re-emerging [ ] - mexico, honduras interactive voice response (ivr) support calls for chronic disease management for spanish speakers-the investigators report cumulative findings in honduras, mexico, and spanish-speakers in the u.s. involvement of caregivers enhanced engagement. by self-report, there was improved medication adherence and self-management was similar across sites. piette, [ ] honduras cloud-computing model -the investigators tested a mobile phone-based intervention of weekly voip calls and ivr with patients with diabetes and automated emails to clinicians and voicemail reports to family caregivers for six weeks. improved self-care and diabetes management and significant improvement in glycemic control were reported. piette, [ ] bolivia structured caregiver feedback -the investigators assessed whether automated telephone feedback to caregivers ("carepartners") increased engagement in mobile-health support among patients with diabetes and hypertension in bolivia. significantly greater engagement was observed. patients who spoke indigenous languages at home were more than x as likely to complete the ivr calls. piette, [ ] bolivia mobile health program for chronic disease self-management in bolivia -assessment and implementation of ivr for weeks. it was associated with improved medication adherence, self-reported health status, and satisfaction. prestes, [ ] - argentina diapremintegrated diabetes care program including systemic changes education, registry and disease management flood, [ ] guatemala implementation and outcomes of a comprehensive type diabetes program in rural guatemala through a non-government organization and involving nurse-directed care flood, [ ] rural guatemala implementation of a multi-level quality improvement program for ambulatory diabetes care based on input from patients and other stakeholders flood, [ ] - rural guatemala home-based type diabetes self-managementintervention delivered by diabetes educator at home and synchronized with clinic follow-up. mayan communities tapia-conyer, [ ] gallardo-rincón, [ ] to present mexico casalud model -is a comprehensive primary health care model implemented in mexico that enables proactive prevention and disease management using innovative technologies and a patient-centered approach. the program was pilot tested in and implemented nationwide in . infectious diseases, like tuberculosis [ ] [ ] [ ] . therefore, disease prevention and health care models that account and reach these populations need to be considered. through this review, we have highlighted the most current reports on prevalence, awareness, treatment, control, and adherence to recommended guidelines of care for diabetes mellitus across latam published from to . during that time frame, a considerable number of surveys assessing the prevalence of the disease and an increasing body of reports on the achievement of treatment and care goals were identified. such reports demonstrate the imperative need to garner a more comprehensive understanding of the extent of diabetes across countries, and both past and ongoing efforts to establish effective and sustainable models of prevention and high-quality care able to reach and serve all peoples across the region. during the writing of this manuscript, latin america had been recognized as the new epicenter of the sars-cov- (covid- ) pandemic [ ] . the effects of the disease in persons with diabetes in the region are beginning to be uncovered [ ] [ ] [ ] , while some solutions are proposed [ , ] . the magnitude of the impact of the pandemic on the health and health care needs of persons with diabetes mellitus and other ncds-let alone on the health care systems infrastructures-in the region are yet to be known. the task ahead is substantial and will require multidisciplinary and cross-sectoral strategies and collaborations to reduce diabetes burden and improve health outcomes across latin america. acknowledgments the authors would like to thank ms. jill pope (kaiser permanente center for health research) for her valuable review of the manuscript and the ponce health sciences university for creating the opportunity for am-r and as-s to work in this review. understanding the rise of cardiometabolic diseases in low-and middle-income countries global burden of diabetes, - : prevalence, numerical estimates, and 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region) critical review of social, environmental and health risk factors in the mexican indigenous population and their capacity to respond to the covid- covid- pandemic triggers telemedicine regulation and intensifies diabetes management technology adoption in brazil publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- - kozsv z authors: dewidar, bedair; kahl, sabine; pafili, kalliopi; roden, michael title: metabolic liver disease in diabetes – from mechanisms to clinical trials date: - - journal: metabolism doi: . /j.metabol. . sha: doc_id: cord_uid: kozsv z abstract non-alcoholic fatty liver disease (nafld) comprises fatty liver (steatosis), non-alcoholic steatohepatitis (nash) and fibrosis/cirrhosis and may lead to end-stage liver failure or hepatocellular carcinoma. nafld is tightly associated with the most frequent metabolic disorders, such as obesity, metabolic syndrome, and type diabetes mellitus (t dm). both multisystem diseases share several common mechanisms. alterations of tissue communications include excessive lipid and later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis and ectopic fat deposition in skeletal muscle. on the hepatocellular level, this leads to insulin resistance due to abnormal lipid handling and mitochondrial function. over time, cellular oxidative stress and activation of inflammatory pathways, again supported by multiorgan crosstalk, determine nafld progression. recent studies show that particularly the severe insulin resistant diabetes (sird) subgroup (cluster) associates with nafld and its accelerated progression and increases the risk of diabetes-related cardiovascular and kidney diseases, underpinning the critical role of insulin resistance. consequently, lifestyle modification and certain drug classes used to treat t dm have demonstrated effectiveness for treating nafld, but also some novel therapeutic concepts may be beneficial for both nafld and t dm. this review addresses the bidirectional relationship between mechanisms underlying t dm and nafld, the relevance of novel biomarkers for improving the diagnostic modalities and the identification of subgroups at specific risk of disease progression. also, the role of metabolism-related drugs in nafld is discussed in light of the recent clinical trials. finally, this review highlights some challenges to be addressed by future studies on nafld in the context of t dm. nonalcoholic fatty liver diseases (nafld) is currently defined by lipid deposition that exceeds more than % of hepatocytes, as assessed from liver biopsy, and/or by more than . % hepatocellular fat content per liver weight, as assessed from magnetic resonance (mr) methods, in the absence of significant alcohol consumption and other causes of fatty liver [ , ] . nafld, which affects about % of the population [ ] , comprises a broad range of abnormalities ranging from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (nash), characterized by inflammation, necrosis, and hepatocellular ballooning, and progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma (hcc) [ ] . some gene variants promote risk of nafld by altering lipid droplet formation and de novo lipogenesis (dnl), such as variants of patatin-like phospholipase domain-containing protein (pnpla ) and glucokinase regulatory protein [ ] , or by decreasing very-low-density lipoproteins (vldl) export as shown for a missense mutation (e k) in transmembrane superfamily member (tm sf ) [ ] . nevertheless, nafld is tightly associated with common acquired metabolic diseases such as obesity and type diabetes (t dm). the mutual relationship between both diseases is illustrated by several epidemiological data. the prevalence of steatosis and nash has been estimated to be and %, respectively, in t dm [ ] . the age-adjusted relative risk of nafld is about . fold higher in t dm compared to healthy humans [ ] . t dm is also an emerging risk factor for nash progression to advanced fibrosis, cirrhosis and hcc [ , ] . diabetes was even a better predictor for hcc development in people with nash and cirrhosis compared to other metabolic risk factors such as hyperlipidemia, body mass index (bmi) and hypertension [ ] . recently, a consensus panel has proposed to rename nafld a metabolic-dysfunction-associated fatty liver disease (mafld) based on the presence of overweight/obesity, t dm and evidence of so-called "metabolic dysregulation" [ ] . future will tell, if this will help to better understand the multiple relationships between nafld and t dm. in this context, nafld per se associates with more than double risk of incident diabetes pointing to specific liver-related mechanisms [ , ] . moreover, multicenter studies in skandinavia and germany have recently found that diabetes can be stratified into subtypes j o u r n a l p r e -p r o o f the circulation. on the contrary, a recent study demonstrated that obesity-induced insulin resistance preceded inflammation in adipose tissues of mice [ ] . indeed, adipose tissue inflammation might be a protective feedback mechanism as its local inhibition in mice induced ectopic lipid accumulation in liver, glucose intolerance, and systemic inflammation [ ] . besides released inflammatory cytokines and ffa, adipose tissue could still communicate with the liver and muscle through secretion of different adipokines such as adiponectin and leptin. persons with nash have lower serum adiponectin compared to those with nafld with or without normal liver enzymes [ ] . by contrast, the circulating levels of leptin were higher in people with nafld and t dm, probably due to increased leptin resistance, and were associated with disease severity [ ] . increased ffa influx to skeletal muscle promotes accumulation of intramyocellular lipid (imcl). reduced mitochondrial oxidation contributes as well to imcl as shown in aging and insulin-resistant humans [ ] . consequently, skeletal muscle exhibits insulin resistance, which often precedes the onset of t dm and insulin resistance in the liver [ ] . lipid intermediate metabolites, in particular sn , diacylglycerols (dag), link imcl to skeletal muscle insulin resistance through activation of protein kinase c-theta (pkcθ) resulting in its translocation from cytoplasm to the plasma membrane [ ] . muscles of insulin resistant humans with obesity and t dm showed increased dag content and pkcθ activity as compared to healthy humans [ ] . mutation studies highlighted serine amino acid residue (ser ) of irs to be a substrate for activated pkcθ [ ] . as a consequence of skeletal muscle insulin resistance, postprandial energy storage shifts from glycogen synthesis in the muscle into triacylglycerol (tag) in the liver, promoting nafld development [ ] . gut microbiome is increasingly recognized as a modulator of liver pathogenesis through what is called the "gut-liver axis" [ ] . distinctive alterations of gut microbiome were reported in humans having nash and t dm [ ] . the intestinal microbiome alters host metabolism by modulating the production of short-chain fatty acids (scfa) e.g. butyrate, acetate, and propionate, which have beneficial effects on insulin sensitivity, lipid and glucose metabolism [ ] . also, intestinal dysbiosis could associate with increased intestinal permeability permitting translocation of bacterial lipopolysaccharide (lps) into the systemic circulation, j o u r n a l p r e -p r o o f which could induce fat deposition in the liver, nash progression, weight gain, and diabetes [ ] . moreover, intestinal microbiome could suppress the expression of fasting-induced adipocyte factor (fiaf) in intestinal epithelium, which functions as an inhibitor of circulating lipoprotein lipase, resulting in increased tag storage in the peripheral tissues [ ] . also, ethanol-producing microbiome could increase blood alcohol concentration in nash, which is metabolized in the liver generating high levels of reactive oxygen species (ros). the last mechanism could explain the histological similarity between nash and alcoholic steatohepatitis [ ] . furthermore, microbiota metabolize liver-derived primary bile acids into secondary bile acids. the latter are reabsorbed into bloodstream and may act as signaling molecules via a variety of receptors including farnesoid x receptor (fxr), which regulates the transcription of different metabolic genes involved in bile acid synthesis, transport, lipogenesis, and glucose homeostasis [ ] . insulin resistance in both skeletal muscle and adipose tissues initiates liver steatosis by providing precursors and substrates for dnl and mitochondrial β-oxidation e.g. glucose, ffa and glycerol [ ] . although reesterification of ffa derived from diet and adipose tissue is the dominant contributor to tag pool in the liver ( %), it did not increase in people with nafld. on the other side, dnl-derived ffa contribute by about %, which is severalfold higher as compared to individuals without nafld ( %) [ ] . later, insulin resistance of the liver develops, resulting in increased gluconeogenesis and elevation of endogenous glucose production (egp) from the liver, which contributes to fasting hyperglycemia in individuals with t dm [ ] . insulin signaling inhibits typically hepatic gluconeogenesis through akt-induced phosphorylation of forkhead box (foxo ) and induces lipogenesis through activation of sterol regulatory element-binding proteins (srebp c) and mammalian target of rapamycin complex (mtorc ) pathways. during hepatic insulin resistance, insulin does not suppress gluconeogenesis efficiently, while dnl is preserved or even increased. to explain this discrepancy, pathway-selective hepatic insulin resistance was postulated, which means that only one arm of insulin signaling is defective i.e. akt/foxo leading to reduced insulin-mediated suppression of gluconeogenesis, whereas insulin-activated srebp- c/mtorc pathway remains intact and activates lipogenesis [ ] . actually, dnl was reduced after induction of hepatic insulin resistance by feeding mice with j o u r n a l p r e -p r o o f a high-fat diet (hfd) [ ] , which challenges the concept of selective hepatic insulin resistance and suggest the existence of alternate mechanisms that contribute to increased dnl and gluconeogenesis in insulin-resistant liver, for example, hyperinsulinemia, insulinindependent re-esterification of adipose tissue-derived ffa, and increased acetyl coa generation from β-oxidation of ffa, which allosterically activates pyruvate carboxylase enzyme, leading to enhanced gluconeogenesis [ ] . in addition, increased blood glucose level can activate carbohydrate response element-binding protein (chrebp) signaling pathway, thereby stimulating expression of several glycolytic genes, which provide additional metabolic precursors for dnl [ ] . in line, chrebp overexpression induced stearoyl-coa desaturase (scd ) expression, an enzyme responsible for the biosynthesis of monounsaturated fatty acids (mufa), resulting in increased liver fat content [ ] . pkc epsilon (pkcε) is crucial in mediating hepatic insulin resistance and once activated by dag, it translocates to the cell membrane, and phosphorylates specific threonine residue (thr in human and thr in mouse) on insulin receptor leading to destabilization of the active configuration of insulin receptor kinase and inhibition of its tyrosine kinase activity [ ] (figure ). in general, both hyperglycemia and toxic lipids such as ceramides, dag, ffa, and cholesterol can induce deleterious effects on liver cells (glucolipotoxicity), which might initiate nafld progression from simple steatosis to nash and fibrosis via various mechanisms, including cell death, oxidative stress, endoplasmic reticulum (er) stress and mitochondrial disorders [ ] . alterations in the activity and abundance of oxidative phosphorylation (oxphos) proteins and antioxidant enzymes were described in various animal models of nafld [ ] . impaired hepatic mitochondrial function was evident as well in t dm and nash [ , ] . in a mouse model of choline-deficient diet-induced nafld, mitochondrial oxphos was increased at weeks but lost at a later time point [ ] . also, the higher maximal respiration rate of liver mitochondria was severalfold higher in insulin-resistant obese individuals with fatty liver as compared to lean individuals [ ] . these studies highlight the flexibility of mitochondria to adapt to increased metabolic inputs to keep energy homeostasis and to protect against the harmful effects of increased ffa and tag in the liver. in nash, mitochondrial flexibility was lost, which was associated with increased ros production and exhaustion of protective antioxidant enzymes [ ] (figure ). whether loss of mitochondrial flexibility is a cause or consequence for nafld progression remains obscure. depletion of atp due to j o u r n a l p r e -p r o o f mitochondrial disorders, together with hyperglycemia and lipid overload could be inducers for another signaling pathway, termed unfolded protein response "upr", which is adaptive response to resolve unfolded or misfolded proteins and to restore er homeostasis [ , ] . prolonged upr stress can activate jnk and nf-kb signaling pathways, which are involved in insulin resistance, liver steatosis, and inflammation [ ] . furthermore, er stress could increase insulin resistance through induction of lipin- expression, which is a phosphatase enzyme that catalyzes biosynthesis of dag leading to activation of dag/pkcε axis [ ] . interestingly, upr could also increase liver steatosis through activation of srebp- c signaling pathway [ ] . elevated ros and upr are well-identified pathways that could induce hepatocytes death in nash. hepatocytes apoptosis and necroptosis are the main forms of cell death in human steatohepatitis and diet-induced mouse models of nash [ ] . the key fibrogenic liver cells, hepatic stellate cells (hscs), usually exist in a quiescent state and get activated by engulfment of apoptotic bodies, the inflammatory milieu, or damage-associated molecular patterns (damps) released from stressed and dying hepatocytes [ ] . interestingly, ffa-mediated lipotoxic effects stimulate hepatocytes to release extracellular vesicles (evs) with distinctive micrornas (mirna) profile that increase the expression of fibrogenic genes in the surrounding hscs [ ] (figure ). free cholesterol could directly sensitize hscs to the action of tumor growth factor (tgf)-β, a potent fibrogenic cytokine [ ] . treatment of human and rat immortalized hscs cell lines with saturated fatty acid increased the expression of various profibrogenic genes [ ] . macrophages aggregate as well around dead hepatocytes forming a crown-like structure, a phenomenon that exists only in persons with nash but not in those with simple steatosis [ ] . recruitment of more inflammatory cells from systemic circulation is facilitated by "find me" signals that are released from dead cells [ ] . inhibition of inflammatory monocytes recruitment via inhibition of c-c chemokine receptors type and type (ccr /ccr ) suppressed fibrogenesis and steatohepatitis in murine nash [ ] . macrophages can modulate also hepatic insulin resistance and favor tag accumulation in hepatocytes through secretion of il- β that downregulates peroxisome proliferator-activated receptor (ppar) α, a key transcriptional pathway involved in fatty acid oxidation [ ] . liver sinusoidal cells (lsecs) are fenestrated cells that exist in close vicinity to hepatocytes, j o u r n a l p r e -p r o o f macrophages and hscs, which, under physiological conditions, regulate lipid transport, maintain the quiescence of kupffer cells, resident liver macrophages, and hscs [ ] . at early stage of nafld, lsecs lose their fenestrae, a process termed capillarization, which could favor liver steatosis and initiate hscs activation [ ] (figure ). during nash, lsecs display a pro-inflammatory phenotype that promotes steatohepatitis [ ] . autophagy is a self-degradative process which is used by the cells to remove misfolded proteins and damaged organelles [ ] . singh et al. showed that the cells can use autophagic process as lipolytic mechanism to mobilize lipids from intracellular lipid store, which is termed in this case "macrolipophagy" [ ] . various in vitro and in vivo studies showed that autophagy was decreased in fatty hepatocytes [ ] . impairment of autophagy by palmitic acid in macrophages induces inflammatory il- β production [ ] . on the other side, selective loss of autophagic activity reduced liver fibrogenesis in cultured hscs [ ] and protected against diet-induced insulin resistance [ ] . the results highlight that the net effect of autophagy on nafld might depend on the tissue or type of the cells that show autophagic dysfunction and the stage of nafld. the liver biopsy is considered the gold standard for nafld diagnosis, especially for distinguishing steatosis from inflammation and fibrosis [ ] . nevertheless, this technique has several limitations not only resulting from the invasive procedure and rare post-interventional complications, but also due to the small tissue volume, which might not be representative for the whole liver and may not take into account inhomogeneous distribution of nafldassociated alterations. novel imaging modalities such as ultrasound-or mr-based techniques are of increasing value, as recently reviewed [ ] , but are still not generally available, so that there is an urgent need for noninvasive screening tools. non-invasive detection of nash and fibrosis remains challenging today. biomarker-based panels such as aspartate aminotransferase (ast)/platelets count ratio index, fibrosis- (fib- ) index, fibrotest, fibrospect ii, and nafld fibrosis score (nfs) offer variable diagnostic efficacy for assessing different stages of liver fibrosis [ , ] . although combination of these panels could enhance their predictive values [ ] , they still suffer from limited accuracy even compared to the alanine aminotransferase (alt) and ast, particularly in t dm [ ] . in this regard, transient elastography looks like a promising alternative in diabetes clinics for detection of liver fibrosis in nafld [ ] . numerous biomarkers have been developed to specifically track features of nash progression and fibrosis. cytokeratin (ck) , an intermediate filament protein that is cleaved during cell death to ck m and ck m , has been intensively investigated as a surrogate of nash-associated liver cell damage, but a recent meta-analysis of studies reported a maximum sensitivity of . for nash diagnosis [ ] and suboptimal diagnostic value was shown in t dm [ ] . the ecm turnover marker, type iii procollagen, can offer a diagnostic efficacy of . and . to detect moderate and advanced liver fibrosis in t dm, respectively [ ] . in , the european associations for the study of the liver, obesity and diabetes (easl-easo-easd) jointly released recommendations for diagnosis and monitoring of disease severity in persons with suspected nafld and metabolic risk factors [ ] . people with metabolic risk factors, such as t dm, should undergo assessment by abdominal ultrasound, serum transaminases and fibrosis markers (e. g. fib- , nfs). elevated transaminases or steatosis plus abnormal fibrosis test shall require referral to a specialist. this strategy has raised the question of a possible overreferral when adhering to these guidelines [ ] . however, recent analyses show that a refined strategy of specific combining indices such as fli and fib- could reduce the number of people with t dm for further diagnostic work up to a reasonable size [ ] . this retrospective analysis also found that certain non-invasive biomarkers are consistently associated with different patterns of diabetes-related complications. analyses of the plasma metabolomic of insulin-resistant individuals with nafld suggested that bile salts, e. g. glycocholate, taurocholate, and glycochenodeoxycholate allow to detect nash in one study [ ] , while another study reported an association with insulin resistance j o u r n a l p r e -p r o o f but not with liver necroinflammation [ ] . also amino acids, specifically a glutamate-serineglycine index, was associated with hepatic insulin resistance and transaminases and discriminated individuals with fibrosis grade - from those with grade - independently of bmi [ ] . the diagnostic performance of a serum-based lipidomic analysis was substantially lower for nafld detection in t dm compared to healthy individuals [ ] . nevertheless, certain sphingolipid species were recently found to be increased in insulin-resistant nash and to correlate with hepatic oxidative stress and inflammation [ ] . one circulating small noncoding rna, mirna- , was found to be more than . fold in steatosis and further doubled in nash [ ] . this mirna was also higher in t dm with nafld than in those without nafld and provided better prediction of nafld when combined with ldl and waist-to-hip ratio [ ] . moreover, extracellular vesicles (ev), which among other cargo also transport mirna, may be promising biomarkers for nafld as shown by higher serum levels in people with nafld, obesity and diabetes [ ] . recently, metagenomics data derived from gut microbiota alterations allowed to detect advanced fibrosis in nafld patients, of whom % had t dm, with a robust diagnostic accuracy (auroc: . ) [ ] . the current guidelines recommend only lifestyle modification and -for certain groupsbariatric or metabolic surgery to treat nafld [ , ] . although the numerous activities in this field, no pharmacological treatment is currently approved or expecting approval for the use in nafld with or without concomitant t dm (table and ), except for obeticholic acid (oca). marketing authorization application for oca has been submitted to the u.s. food and drug administration (fda) and european medicines agency (ema), awaiting fda decision by june [ ] . against this background, current guidelines and recommendations primarily advise lifestyle modification (healthy nutrition and exercise) and weight loss in overweight/obese persons. the easl-easo-easd guidelines recommend to consider pharmacological treatment in people with nash when combined with fibrosis and in those with less severe disease, but high risk conditions for disease progression such as t dm [ ] . the american association for the study of liver diseases (aasld) recommends to limit pharmacological treatment to those with biopsy-proven nash and fibrosis [ ] . j o u r n a l p r e -p r o o f weight management and physical exercise are key to the treatment of both nafld and t dm. a proof-of-concept study showed that a hypocaloric diet with weight loss of ~ kg within weeks not only normalized fasting egp and thereby hyperglycemia, but decreased hepatic tag content down to normal concentrations in obese t dm humans with nafld [ ] . subsequent studies in larger cohorts extended these results by demonstrating that a very low-caloric diet with weight loss of about % rapidly normalized liver fat content in in dividuals with t dm, which persisted for one year if weight loss was maintained [ ] . interestingly, mediterranean, low-saturated fat and high plant-based protein diets also improve steatosis in nafld combined with t dm despite minor or no relevant weight loss [ , ] . in addition, physical activity and exercise training interventions can also decrease liver fat content, which may not be exclusively depending on concomitant weight loss [ ] . although the beneficial effects of structured behavioral treatment to improve histological endpoints, likely extend beyond reduction of hepatic fat content to ameliorating the grade and stage of inflammation and fibrosis [ ] , only a minority of the people manages to adhere to dietary weight loss and exercise programs, which raises the issue of other therapeutic approaches [ ] . weight-loss inducing drugs could be an attractive option for persons with nafld with a bmi > kg/m or > kg/m in the presence of at least one metabolic comorbidity, as an adjunct treatment to lifestyle modifications [ , ] . currently, the most-popular weight-loss inducing medications associated with at least % body weight decrease in one year as compared to placebo are orlistat, the fixed combination of phentermine and topiramate or naltrexone and bupropion, and the glucagon-like peptide- (glp- ) receptor agonist (glp- ra), liraglutide [ ] . of these drugs, orlistat treatment failed to improve liver histology when compared to placebo [ ] , while no reports are available for topiramate, naltrexone, bupropion and phentermine regarding hepatic endpoints in humans with nafld [ ] . only bariatric or metabolic surgery is a therapeutic option to induce sustained weight loss partricularly in people with combined nafld and t dm. in obese humans, bariatric surgery resulted in % resolution of nash within one year [ ] and in % complete remission of t dm [ ] . surgical weight loss improves glucose metabolism and insulin sensitivity by different mechanisms such as increased glp- secretion [ ] and epigenetic modification [ , ] . several antihyperglycemic drug classes were or are currently being investigated in clinical trials and preclinical models to evaluate their efficacy for people with nafld and with or without t dm. metformin reduces body weight, hepatic gluconeogenesis -by yet unclear mechanisms [ ] , and the risk of macrovascular complications, which is still controversially discussed due to lack of optimally designed clinical trials [ ] . despite its action on hepatic metabolism, former small-scale studies reported conflicting results [ , ] (table ) and recent metaanalysis failed to demonstrate any effect of metformin on liver histology [ ] . nevertheless, epidemiological, observational and preclinical studies suggest that metformin may reduce the risk of hcc and also in t dm, possibly by promoting apoptosis, but controlled clinical trials are not available [ ] . dpp degrades incretins such as glp- so that dpp- i treatment increases the postprandial levels of endogenous glp- , which leads to lower glucose peaks after meals [ , ] . in individuals with nafld with prediabetes or recent onset diabetes, sitagliptin did not improve liver steatosis or liver fibrosis compared to placebo as assessed by mr-based techniques [ ] . in line, another recent trial reported no benefits for sitagliptin versus placebo on liver fibrosis or steatohepatitis in t dm [ ] (table ) . in contrast, a moderate reduction in liver fat content was observed with vildagliptin in individuals with t dm [ ] . j o u r n a l p r e -p r o o f the actions of endogenous glp- are mimicked by glp- receptor agonists (glp- ra), which effectively reduce blood glucose levels and also reduce the risk for cvd in t dm [ ] . in individuals with nafld and t dm, liraglutide in combination with metformin reduced liver, subcutaneous, and visceral fat [ ] . also, liraglutide improved hepatic steatosis measured by mr-based methods as well as resolved biopsy-proven nash without worsening of fibrosis [ , ] (table ) . however, a recent subanalysis did not detect an effect of liraglutide on liver fat content quantified by h-mrs [ ] (table ) . respective trials with semaglutide and dulaglutide are still waiting for results (nct , nct ). in an animal model of t dm, exenatide also counteracted hcc development by suppression of stat -regulated genes [ ] . glucose-dependent insulinotropic polypeptide (gip) represents the second important incretin with proposed beneficial effects on peripheral energy metabolism [ ] . tirzepatide, a novel dual agonist for gip and glp- receptors with probably greater efficacy than glp- ra [ ] , decreased transaminases and surrogate markers of liver injury paralleled by increased circulating adiponectin levels in people with t dm [ ] . a clinical trial on nash resolution is currently ongoing in persons with nash with or without t dm (nct ). sglt i inhibit reabsorption of glucose in the proximal renal tubule resulting in glucosuria and calory loss, thus effectively reducing blood glucose level and body weight in t dm. moreover, sglt is show beneficial effects on cardiovascular risk and progression of nephropathy [ , ] . most, but not all recent randomized controlled trials (rcts) showed that sglt i treatment resulted in reduction in liver fat content compared to placebo [ ] [ ] [ ] [ ] [ ] (table ) . in an open-label pilot study in liver-biopsy proven cohort of nash with t dm, treatment with empagliflozin for months reduced liver steatosis, ballooning and fibrosis and induced nash resolution in approximately half of those persons [ ] . animal models further suggested anti-inflammatory, anti-oxidant and pro-apoptotic actions of sglt i with cardio-protective effects as well as inhibition of nash progression and tumor growth of hcc [ , ] . the dual sglt / i, licogliflozin, is expected to block both intestinal and renal glucose (re)absorption [ ] and currently investigated to evaluate its efficacy on resolution of nash as monotherapy and as combination therapy with the fxr agonist, tropifexor, in people with nash and fibrosis (nct ). first results hint at improvement of transaminases and reduction of steatosis by licogliflozin in nash [ ] . ppars is a family of nuclear receptors composed of multiple isoforms with wide tissue distribution [ ] . the ppar-γ agonist pioglitazone had convincing efficacy on nash resolution in individuals with and without t dm, but with conflicting results on fibrosis [ ] [ ] [ ] (table ) . of note, pioglitazone has been withdrawn in many european countries because of its disadvantageous safety profile [ ] . however, pioglitazone exerts beneficial effects on cardiovascular outcomes in persons with t dm and a history of cvd [ ] . it has been proposed that non-ppar-γ dependent mechanisms, as the inhibition of the mitochondrial pyruvate carrier (mpc), might mediate the beneficial effects of pioglitazone on nafld [ ] . however, a novel drug with ppar-γ sparing effects and mpc binding activity did not improve histological components of nash in individuals with t dm compared to placebo [ ] . elafibranor is a dual agonist for ppar-α and ppar-δ without ppar-γ stimulation [ ] . based on a post-hoc analysis, nash was resolved without worsening of fibrosis in a higher percentage of people with and without t dm in the elafibranor group as compared to the placebo [ ] and a follow-up study on these findings has been initiated ( table ) . recent announcements on an interim analysis state that elafibranor treatment failed to resolve nash and improve fibrosis when compared to placebo [ ] . saroglitazar is another dual ppar-α/γ agonist with higher affinity for ppar-α. in a mouse model of nash, saroglitazar reduced liver steatosis, inflammation and prevented fibrosis development and a respective clinical trial is ongoing [ ] ( table ) . lanifibranor is a pan-ppar agonist for ppar-α, β, and γ receptors focused on treatment of liver fibrosis and nash (nct ). in an animal model of liver fibrosis, lanifibranor decreased hepatic collagen deposition [ ] . several other strategies for pharmacological targeting of nash have emerged over the last few years; however, these strategies are not specifically designed for t dm, but for the whole nafld collective. they comprise antiinflammatory drugs, but also modulators of other pathways, which are briefly summarized in the following sections. j o u r n a l p r e -p r o o f fxr can be activated by bile acids in a negative feedback mechanism to suppress bile acid synthesis [ ] . oca is a potent semisynthetic and selective fxr agonist approved for treatment of primary biliary cholangitis [ ] . oca treatment resulted in histologic improvement of nash in people with and without t dm compared to placebo [ , ] ; however, concerns were raised about oca-induced changes in plasma lipoprotein profile [ ] . tropifexor, another potent fxr agonist [ ] , is currently being tested in combinatorial approaches of nash treatment (cenicriviroc and licogliflozin; nct ). oltipraz is a synthetic dithiolethione with antisteatotic effects by inhibiting the activity of lxr-α. it activates adenosine monophosphate activated protein kinase (ampk) and inactivates s k , affecting lxr-α thus reducing lipogenesis and increasing lipid oxidation [ ] . a recent -week phase clinical trial found decreased steatosis measured by h-mrs with oltipraz compared to placebo treatment [ ] and a respective phase clinical trial is ongoing ( table ). chemokine receptors type (ccr ) and type (ccr ) are expressed on various inflammatory and fibrogenic cells [ ] . cenicriviroc is a ccr /crr dual antagonist that reduced insulin resistance, liver inflammation and fibrosis in diet-induced models of nash [ ] . in recent rcts in a nash cohort with fibrosis, cenicriviroc treatment did not improve nas but may reduce liver fibrosis [ , ] . currently, there is an ongoing clinical trial to evaluate the effects of cenicriviroc on fibrosis in nash ( table ) . both people with obesity, metabolic syndrome or t dm as well as those with nafld are at increased risk for dyslipidemia. statins, inhibitors of -hydroxy- -methyl-glutaryl-coenzyme a (hmg-coa) reductase, are generally safe and have unmet efficacy to decreased serum ldl and prevent cardiovascular outcomes, despite slightly increasing the risk of t dm [ ] . use of statins associated with a % lower relative risk of hepatic decompensation and mortality in cirrhosis and a trend towards lower fibrosis progression in non-cirrhotic liver diseases [ ] . however, the data on liver histology ist limited [ ] so that statins are not currently recommended for the management of nafld [ ] . the inhibitor of intestinal j o u r n a l p r e -p r o o f cholesterol absorption, ezetimibe, decreased the histological nas, but not consistently liver fat content in an analysis of the few available studies [ ] . fenofibrate, a ppar-α agonist, does not affect or even increase liver fat content or volume [ , ] . nevertheless, the combination of statins with certain anti-nash drugs, such as oca, could be beneficial to counteract drug-related increases in ldl during long-term treatment. inhibition of dnl in nafld may be achieved by inhibition of acc as this enzyme catalyzes the conversion of acetyl coa into malonyl coa, which acts as a substrate for fatty acid synthesis and inhibitor for fatty acid β-oxidation [ ] . in a recent clinical trial in individuals with nash with and without t dm, treatment with the dual acc and acc inhibitor gs- decreased liver steatosis without improvement of fibrosis [ ] . the major concern of this strategy is that decreased dnl in nafld might channel lipids towards other harmful directions, e.g. increased blood lipids [ ] . scd is a key enzyme for hepatic lipogenesis that catalyzes the conversion of saturated fatty acids to mufa and its downregulation protected mice from high carbohydrate-induced liver steatosis [ ] . a clinical trial with aramchol, an inhibitor of scd , showed a reduction in liver fat content, resolution of nash and improvement of liver fibrosis in persons with nafld with prediabetes or t dm [ ] . these results paved the way for a respective phase clinical trial ( table ) . mitochondrial uncoupling describes any process that uncouples the electron transport from atp synthesis in mitochondria [ ] . , -dinitrophenol (dnp) was widely used for the treatment of obesity before its discontinuation due to life-threatening serious adverse events [ ] . to overcome the side effects of dnp, improved formulas of dnp were recently developed to decrease the toxic to effective dose ratio (dnp-methyl ether (dnpme) and controlled-release mitochondrial protonophore (crmp)) [ , ] . oral crmp targets mainly the liver due to the first-pass effect and decreased hepatic insulin resistance, hepatic steatosis and liver fibrosis in a methionine-choline deficient rat model of nash [ ] . crmp was also effective in nonhuman primates with diet-induced nafld for reduction of hepatic steatosis and egp [ ] . thyroid hormone deficiency has been associated with nafld development [ ] . thyroid hormone analogues decreased liver fat, liver transaminases, and inflammatory and fibrosis markers in animal models of nash [ ] . resmetirom is a liver-targeted highly selective thr-β agonist which showed efficacy in reducing liver fat content in nash with and without t dm [ ] . currently, there is ongoing clinical trial for evaluation of long-term outcomes of resmetirom and its efficacy on nash resolution ( table ). vitamin e is a potent antioxidant [ ] . in nash without t dm, vitamin e improved nas without worsening of fibrosis [ ] . despite concerns regarding adverse effects of long term vitamin e usage, treatment with vitamin e for ≥ years reduced the risk of liver failure in a nash cohort with advanced fibrosis and with or without t dm [ ] . therapeutic manipulation of intestinal microbiome is still in its infancy. rodent data showed efficacy for fecal microbiota transplantation in improving nafld in a diet-induced nash model [ ] . also, modulation of the intestinal microbiota by antibiotic treatment reduced liver transaminases in nafld [ ] . the use of prebiotics and probiotics in obese nafld/nash is currently not supported by high-quality clinical studies with mr-or biopsy-based endpoints [ ]. the evidence for shared pathophysiological mechanisms between t dm and nafld will help to develop strategies for detecting and treating both diseases and preventing their leading complication, cvd. altered lipid and energy metabolism, insulin resistance, low-grade inflammation and intestinal dysbiosis represent key targets. in addition to weight loss by lifestyle modification or bariatric surgery, glp- ra and sglt i are promising antihyperglycemic concepts with beneficial effects on nafld and cvd. in addition, many j o u r n a l p r e -p r o o f metabolism-based drugs are currently studied comprising ppar agonists, endocrine dual coagonists to modulators of hepatic metabolism or microbiota. nevertheless, several roadblocks need to be overcome to reduce the burden of nafld in t dm. first, there is still lack of preclinical animal models that encapsulate essential features of human nash and diabetes. second, available biomarkers lack diagnostic efficacy to identify nafld progression. innovative strategies such as cluster analysis already enabled detection of a diabetes subtype (sird) with high risk of nafld [ ] . combination with computational integration of multiomics data shall identify specific disease signatures and pave the way to precision medicine and targeted management of t dm and nafld. finally, studies on so-called endpoints are scarce, which may be due to the need of long-term studies to evaluate liver-related mortality, to the current neglect to accept cvd morbidity and mortality as nafld outcome and to ongoing discussions on the relevance of surrogate markers. the research of the authors is supported in part by grants from the german federal ministry phase iii registered interventional trials on "clinicaltrials.gov" for nafld as accessed on th april . bl, baseline; ccr / , c-c chemokine receptors type and type ; fxr, farnesoid x receptor; hba c , glycated haemoglobin; lxr, liver x receptor; mpc, mitochondrial pyruvate carrier; na, data not available; nafld, non-alcoholic fatty liver disease; nfs, nafld fibrosis score; ppar, peroxisome proliferator-activated receptor; nash, non-alcoholic steatohepatitis; scd, stearoyl-coa desaturase; sglt, sodium-glucose cotransporter; thr, thyroid hormone receptor; t dm, type diabetes. *only placebo-controlled, randomized clinical trials are listed, except for saroglitazar, a -arm 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transplant-free survival and hepatic decompensation among patients with nonalcoholic steatohepatitis and advanced fibrosis total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease key: cord- -gn hg oc authors: infante, marco; ricordi, camillo; fabbri, andrea title: antihyperglycemic properties of hydroxychloroquine in patients with diabetes: risks and benefits at the time of covid‐ pandemic date: - - journal: j diabetes doi: . / - . sha: doc_id: cord_uid: gn hg oc the antimalarial drug hydroxychloroquine (hcq) has long been used as a disease‐modifying antirheumatic drug for the treatment of several inflammatory rheumatic diseases. over the last three decades, various studies have shown that hcq plays also a role in the regulation of glucose homeostasis. although the mechanisms of action underlying the glucose‐lowering properties of hcq are still not entirely clear, evidence suggests that this drug may exert multifaceted effects on glucose regulation, including improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance and reduction of systemic inflammation. preliminary studies have shown the safety and efficacy of hcq (at a dose ranging from to mg/day) in patients with type diabetes over a short‐term period. in , hcq has been approved in india as an add‐on hypoglycemic agent for patients with uncontrolled type diabetes. however, large randomized controlled trials are needed to establish the safety and efficacy profile of hcq in patients with type diabetes over a long‐term period. with regard to the covid‐ pandemic, several medications (including hcq) have been used as off‐label drugs due to the lack of proven effective therapies. however, emerging evidence shows limited benefit from hcq use in covid‐ in general. the aim of this manuscript is to comprehensively summarize the current knowledge on the antihyperglycemic properties of hcq and to critically evaluate the potential risks and benefits related to hcq use in patients with diabetes, even in light of the current pandemic scenario. this article is protected by copyright. all rights reserved. since the s, the antimalarial drugs chloroquine and hydroxychloroquine (hcq) have been used as disease-modifying antirheumatic drugs (dmards) for the treatment of several inflammatory rheumatic diseases, including rheumatoid arthritis (ra) and systemic lupus erythematosus (sle). ( ) importantly, hcq has shown a good safety and tolerability profile in most patients, even during pregnancy and breastfeeding. ( , ) intriguingly, a growing body of evidence coming from studies conducted over the last three decades suggests that hcq plays also a role in the regulation of glucose homeostasis in individuals with and without diabetes. ( ) although the exact mechanisms of action underlying the glucose-lowering properties of hcq are still not entirely clear and may differ between patients with and without diabetes, pre-clinical and clinical data suggest that hcq could exert multifaceted effects on glucose homeostasis, namely: improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance and intracellular insulin and insulin-receptor complex degradation, increase of adiponectin levels, reduction of systemic inflammation, and/or reduction of inflammation-induced insulin resistance in adipocytes and skeletal muscle cells. ( ) ( ) ( ) in this regard, a randomized study is currently underway at washington university (metahcq, metabolic effects of hydroxychloroquine; clinicaltrials.gov identifier: nct ) to evaluate the effects of - week hcq administration (at a dose of mg/day) on insulin sensitivity (determined by this article is protected by copyright. all rights reserved. accepted article hyperinsulinemic euglycemic clamp), fasting blood glucose, lipid profile and serum biomarkers of inflammation in subjects with t d. remarkably, several studies demonstrated that hcq use is associated with a significantly reduced risk of developing diabetes in non-diabetic subjects with inflammatory rheumatic diseases, including ra, ( ) ( ) ( ) sle, ( ) psoriasis, ( ) and sjögren syndrome. ( ) in the early s, an italian -month randomized, placebo-controlled trial conducted by quatraro et al. ( ) in t d subjects first showed that the addition of hcq ( mg/day) to glibenclamide or insulin led to a significant reduction in glycated hemoglobin (hba c), accompanied by a % reduction in daily insulin dose among patients on insulin therapy. thereafter, a canadian randomized, placebo-controlled trial conducted in obese patients with t d refractory to sulfonylureas showed that the addition of hcq (up to a maximum of mg bid) reduced hba c by an absolute amount of . % more than placebo after months. ( ) no significant hcq-related side effects were reported in these studies, except for a severe hypoglycemic episode occurred in one patient treated with hcq in combination with insulin. ( ) moreover, a retrospective study conducted in diabetic patients with concomitant rheumatic diseases (ra and sle) showed that hcq, when compared to methotrexate, was associated with a significantly greater reduction in hba c from pre-treatment baseline to its lowest value within months of treatment initiation. ( ) more recently, a -week prospective randomized trial ( ) and two real-world, prospective observational studies of short duration (up to - weeks) ( , ) conducted in india have shown that the use of hcq ( mg/day) as an add-on treatment in patients with t d uncontrolled on a combination of two or more oral hypoglycemic agents (including metformin, sulfonylureas, pioglitazone, dpp- inhibitors, sglt inhibitors, and alpha-glucosidase inhibitors) was welltolerated and led to a significant improvement of glucose control (assessed by hba c, fasting-and postprandial blood glucose) from baseline (without occurrence of severe hypoglycemia). this article is protected by copyright. all rights reserved. in india, diabetes has reached epidemic proportions over the last years and newer antidiabetic drugs pose affordability challenges due to their high cost. based on the aforementioned preliminary results, hcq (at a dose of mg/day) has been approved in by the drug controller general of india (dcgi) as a third-line (add-on) hypoglycemic agent for patients with inadequately controlled t d despite lifestyle management associated with sulfonylurea and metformin combination therapy. ( , ) thereafter, a vibrant debate about hcq safety in t d has arisen within the indian scientific community. ( ) ( ) ( ) ( ) animal and human studies support the existence of different molecular mechanisms underlying the antihyperglycemic properties of hcq (and chloroquine). a study conducted by halaby et al. ( ) in cultured rat muscle cells and in a rat model of insulin resistance demonstrated that chloroquine can promote insulin-mediated glucose uptake and glycogen synthase activity by activating akt. in , powrie et al. ( ) conducted a randomized, placebo-controlled trial in patients with t d (referred to as "non-insulin-dependent diabetes mellitus") who were not receiving any antidiabetic medication and were only adopting dietary measures for diabetes management. the authors performed a hyperinsulinemic euglycemic clamp before and after a -day treatment with chloroquine ( mg administered four times daily) or placebo, using a stable isotopically labelled d-glucose to calculate hepatic glucose production (ra, rate of glucose appearance) and glucose utilization (rd, rate of glucose disappearance). notably, chloroquine led to a significant reduction in fasting plasma glucose and a significant rise in the total amount of exogenous glucose required to maintain euglycemia during the whole experiment, due to an increase in rd (without changes in ra). also, chloroquine administration resulted in a % reduction in metabolic clearance rate of insulin at low-dose insulin infusion. more importantly, fasting c-peptide levels significantly increased throughout the study after chloroquine treatment, despite the initially lower plasma glucose values. a decreased feedback inhibition of c-peptide secretion was also reported during low-and high-dose insulin infusion (by . % and . %, respectively) ( ) . overall, these data suggest that chloroquine can improve fasting glucose levels in subjects with t d by: (i) increasing peripheral glucose disposal (as evidenced by the increased overall glucose infusion rate required to maintain euglycemia, associated with an increase in rd), (ii) reducing hepatic insulin clearance, and (iii) increasing endogenous insulin secretion both in the fasting state and during hyperinsulinemia. the assumption of the authors that chloroquine has a direct insulinotropic effect on pancreatic beta cells is strengthened by the fact that c-peptide has a negligible hepatic clearance and approximately half of the produced c-peptide is metabolized by the kidneys; in particular, the majority of total cpeptide produced is degraded via peritubular uptake and approximately % is excreted unchanged in the urine. ( , ) however, these findings cannot be directly translated to hcq, even though chloroquine and hcq display similar pharmacodynamic properties. ( ) thus, further investigation is warranted in this direction. a study conducted by emami et al. ( ) in diabetic rats showed that hcq increased circulating insulin levels and reduced blood glucose levels in a concentration-dependent manner. in a subsequent study, the same authors found that hcq can inhibit cytosolic insulin-metabolizing enzyme and intracellular insulin degradation in rat liver cells. ( ) in , mercer et al. ( ) showed that hcq therapy (at a dose of . mg/kg/day) for weeks was associated with a significantly increase in insulin sensitivity index (isi) -assessed by a -min oral glucose tolerance test (ogtt) -along with trends toward reduced insulin resistance (assessed by homa-ir) in non-diabetic obese subjects without systemic inflammatory conditions. thereafter, wasko et al. ( ) confirmed similar results in a -week randomized, placebo-controlled study, showing that hcq ( mg/day) improved both beta-cell function (determined by the disposition index) and isi (assessed by intravenous glucose tolerance test) in non-diabetic overweight or obese subjects. at variance with these findings, a randomized, placebo-controlled this article is protected by copyright. all rights reserved. accepted article cross-over trial conducted by solomon et al. ( ) in non-diabetic subjects with stable ra showed that treatment with hcq for weeks (at a dose of . mg/kg/day, and not to exceed mg/day) produced no significant change in isi (assessed by -min ogtt) and insulin resistance (assessed by homa-ir) compared to placebo. these results may indicate that hcq can prevent development of diabetes in patients with inflammatory rheumatic diseases -as it has been widely demonstrated - ( ) ( ) ( ) ( ) ( ) through additional mechanisms other than improvement in insulin sensitivity. hcq is a well-known anti-inflammatory and immunomodulatory agent able to reduce the production of pro-inflammatory cytokines, and is therefore used as a dmard for the treatment of several inflammatory rheumatic diseases. ( , ) with regard to the anti-inflammatory effects of hcq in t d, amit gupta ( ) has recently shown that diabetic patients with higher baseline levels of highsensitivity c-reactive protein (hs-crp > mg/l) exhibited a more pronounced, although not significant, improvement in glucose control from baseline to weeks after the initiation of hcq therapy, as compared to patients with lower baseline levels of hs-crp (≤ mg/l). furthermore, patients with higher baseline hs-crp levels also exhibited higher (although not significant) baseline levels of hba c, fasting-and postprandial glucose levels. ( ) the previously mentioned study by wasko et al. ( ) conducted in non-diabetic overweight or obese subjects also found that hcq (at a dose of mg/day) significantly increased plasma levels of the adipokine adiponectin, which plays a key role in insulin resistance and metabolic syndrome by exerting anti-inflammatory actions and increasing insulin sensitivity. ( ) ( ) ( ) importantly, hcq use up to weeks (at a dose of up to mg/day) in patients with t d has also led to an improved lipid profile, which consisted of a significant reduction in total cholesterol, ldl-cholesterol and non-hdl cholesterol in different studies. ( , , ) a randomized, placebocontrolled cross-over trial also found a significant reduction in total cholesterol and ldlcholesterol after weeks of hcq therapy (at a dose of . mg/kg/day, and not to exceed mg/day) in non-diabetic patients with ra. ( ) nevertheless, it is still not clear whether the potential this article is protected by copyright. all rights reserved. accepted article lipid-lowering properties of hcq may depend on its anti-inflammatory actions rather than on other hcq-related mechanisms. interestingly, type diabetes (t d) trialnet international network is currently investigating the potential ability of hcq to prevent or delay the progression from normal glucose tolerance to impaired glucose tolerance or symptomatic t d in subjects with islet autoimmunity, who are at increased risk of developing t d (clinicaltrials.gov identifier: nct ). therefore, participants enrolled in this study are subjects in the stage (islet autoimmunity) of t d pathophysiology. ( ) however, the current lack of data on safety and efficacy of hcq in patients with established t d does not allow for any conclusion concerning the use of this drug in t d. altogether, these findings suggest that hcq regulates glucose homeostasis by virtue of multifaceted effects, which may allow for classifying this drug as an antidiabetic medication potentially acting as an insulin-sensitizing agent (insulin sensitizer), an anti-inflammatory agent and/or an insulinotropic agent (secretagogue) (figure ). since chronic low-grade inflammation and islet inflammation have been linked to insulin resistance and beta-cell dysfunction in t d, respectively, ( , ( ) ( ) ( ) the anti-inflammatory actions of hcq may be at the interface between its insulin-sensitizing effects and its insulinotropic properties. on the basis of pre-clinical data in animals, hcq appears to have the ability to: (i) inhibit intracellular insulin and insulin-receptor complex degradation, (ii) increase circulating insulin levels, (iii) reduce blood glucose levels, and (iv) promote glucose uptake and glycogen synthase activity in skeletal muscle cells. thus, it is tempting to speculate that hcq is able to inhibit glucagon secretion by pancreatic alpha-cells and/or glucagon action in the liver. additionally, it is still not clear whether the putative effect of hcq on endogenous insulin secretion is mediated by a direct stimulatory effect on beta-cells, and/or by indirect effects involving the reduction of islet inflammation and/or the reduction of glucotoxicityand lipotoxicity-related beta-cell dysfunction following the improvement in metabolic control. moreover, the lack of severe hypoglycemic episodes observed across the studies investigating the this article is protected by copyright. all rights reserved. accepted article use of hcq as an antidiabetic medication in t d (even when hcq was administered in combination with sulfonylureas) may underlie a putative glucose-dependent insulin secretion mechanism mediated by hcq. yet, the occurrence of severe hypoglycemic episodes cannot be excluded in these studies, since they did not employ continuous glucose monitoring. notwithstanding, we believe that all these speculations and unanswered questions may prompt the researchers to conduct future mechanistic studies in order to elucidate the exact mechanisms underlying the antihyperglycemic properties of hcq in both subjects with and without diabetes. even though hcq is considered as one of the safest dmard and has been widely used for the treatment of ra and sle, ( ) data on long-term safety and efficacy of hcq in diabetes are still lacking. therefore, the use of hcq in patients with diabetes should be carefully evaluated, particularly in subjects with established microvascular and/or macrovascular complications. the most dreaded complication deriving from hcq use is retinal toxicity. ( ) however, current evidence suggests that high-dose and long-term (> years) use represent the most important predictors of hcq-induced retinopathy. ( ) therefore, the american academy of ophthalmology recommends a maximum hcq dose of ≤ mg/kg actual body weight per day to markedly minimize the risk of retinopathy. ( ) also, hcq-mediated cardiotoxic effects (including potentially lethal heart rhythm disorders, such as prolonged qt interval, ventricular arrhythmia and torsades de pointes) have been reported. ( , ( ) ( ) ( ) thus, baseline electrocardiography to evaluate for prolonged qt interval is advisable prior to and following the initiation of hcq, particularly in high-risk subjects such as hospitalized patients and individuals taking other qt interval-prolonging drugs (e.g. macrolides such as azithromycin, quinolones, antihistamines, antiviral and antifungal drugs, antiarrhythmic medications, etc.). ( , ( ) ( ) ( ) risk factors for potentially lethal cardiac arrhythmias induced by hcq include: (i) coexisting cardiac conditions such as cardiomyopathy, left ventricular this article is protected by copyright. all rights reserved. accepted article dysfunction, ventricular hypertrophy, coronary artery disease, heart failure, or bradycardia; (ii) history of bradycardia, prolonged qt interval, ventricular arrhythmia or (unexplained) syncope; (iii) family history of premature sudden cardiac death or cardiac ion channelopathies; (iv) pacemaker and implantable cardioverter-defibrillator use; (v) electrolyte abnormalities such as hypokalemia and hypomagnesemia; (vi) genetic and autoimmune channelopathies; (vii) systemic inflammation; (viii) concomitant use of azithromycin or other qt interval-prolonging agents. ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) with regard to the renal function, chronic kidney disease can result in reduced hcq clearance, increased drug bioavailability and subsequent augmented risk of hcq-related side effects. ( ) furthermore, certain drugs (such as tamoxifen, glycosides, methotrexate and ciclosporin) can influence the pharmacokinetics of hcq. ( ) these drug interactions can increase the risk of hcqrelated side effects and therefore require careful consideration. besides the well-known contraindications to hcq use (including known hypersensitivity to aminoquinoline compounds), ( , ) other conditions or circumstances under which hcq should be contraindicated or used with caution in the context of diabetes include the following:  pre-existing retinopathy/maculopathy, history or risk for macular edema, and concomitant use of other oculo-toxic agents. ( , )  diabetes complicated by hypoglycemia unawareness, repeated episodes of severe hypoglycemia and/or malnutrition, due to the potential risk for severe hypoglycemic episodes. although hcqinduced severe hypoglycemia has mainly been documented in non-diabetic subjects, ( ) ( ) ( ) there have been a few reports of severe hypoglycemic episodes occurred with the use of hcq in patients with newly diagnosed t d ( ) and established t d treated with multiple daily injection insulin therapy. ( , )  pre-existing cardiomyopathy or heart failure, due to the possible risk of hcq-related cardiotoxicity. ( ) this article is protected by copyright. all rights reserved.  pre-existing myopathy and/or neuropathy, due to the potential risk of hcq-induced neuromyotoxicity. ( ) ( ) ( ) ( ) ( ) ( )  glucose- -phosphate dehydrogenase (g pd) deficiency, due to the potential increased risk of hcq-related hemolysis crisis. ( ) interestingly, heymann et al. ( ) found a significantly higher proportion of g pd-deficient patients among the diabetic population aged - years. however, a large retrospective study of patients with rheumatic diseases examined the relationship between hcq use and hemolytic anemia in g pd-deficient patients, showing that % of patients had g pd deficiency ( subjects, all african american) and only of them had episodes of hemolysis that occurred while not taking hcq. ( ) based on these findings, authors did not support routine measurement of g pd levels or withholding hcq therapy in african american patients with g pd deficiency. ( ) importantly, a proper risk-benefit assessment of hcq use in diabetic patients should also be considered in relation to the current coronavirus disease (covid- ) pandemic caused by the novel coronavirus sars-cov- (severe acute respiratory syndrome coronavirus ) ( , ) and declared a global pandemic by the who on march , . so far, several medications (including hcq and chloroquine) have been used in hospital settings as off-label drugs for covid- due to the current lack of proven effective therapies. ( , ) however, a recent observational study conducted on , consecutive hospitalized patients with covid- and moderate-to-severe respiratory illness showed that hcq did not have a significant impact on the risk of intubation or death over a median follow-up period of . days. ( , ) despite the observational design of this study, these findings dot not support hcq use for treatment of covid- importantly, diabetes has reached epidemic proportions over the last years, ( ) affecting approximately million people worldwide according to recent estimates. ( ) also, emerging evidence suggests that diabetes represents one of the most prevalent comorbidities in patients with covid- , ( ) ( ) ( ) as well as a major risk factor for a worse prognosis of the disease. ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) in light of these remarks, a pre-emptive and careful evaluation of all the potential risks and benefits related to hcq is critical for a proper and cautious use of this drug in subjects with diabetes, particularly in the context of covid- . over the last decades, several studies have shown that hcq plays an important role in the regulation of glucose homeostasis through multifaceted effects, including improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance and intracellular insulin and insulin-receptor complex degradation, and reduction of systemic inflammation, among others ( figure ). different studies have shown the safety and efficacy of hcq use (at a dose ranging from to mg/day) in patients with t d over a short-term period (up to months). ( , , , , ) in , hcq (at a dose of mg/day) has been approved in india as an addon hypoglycemic agent for patients with inadequately controlled type diabetes despite lifestyle management associated with sulfonylurea and metformin combination therapy. nevertheless, concerns on long-term safety of hcq in patients with t d still persist due to the lack of robust data. thus, large randomized controlled trials of long duration are warranted to establish the longterm safety and efficacy of this drug in the context of t d. with regard to the current pandemic scenario, emerging evidence shows that patients with diabetes have a greater risk for adverse outcomes following covid- infection. although findings from clinical studies have suggested this article is protected by copyright. all rights reserved. accepted article limited benefit from hcq in covid- in general, ( ) several randomized controlled trials are currently investigating the use of hcq for prophylaxis of covid- . ( ) moreover, guidelines from different countries have listed some investigational drugs (including hcq) as potential adjuvant treatment options, whilst cautioning to take into account the individual risk of harm. ( , ) therefore, a careful risk-benefit assessment of hcq is required for the most cautious use of this drug in subjects with diabetes. accepted article without diabetes suggests that hydroxychloroquine regulates glucose homeostasis by virtue of multifaceted effects, including increase of insulin secretion, improvement of insulin sensitivity, reduction of hepatic insulin clearance and intracellular insulin and insulin-receptor complex degradation, increase of adiponectin levels, reduction of systemic inflammation, and/or reduction of inflammation-induced insulin resistance in adipocytes and skeletal muscle cells. altogether, these actions may allow for classifying hydroxychloroquine as an antidiabetic agent by acting as an insulin-sensitizing agent, an anti-inflammatory agent and/or an insulinotropic agent (secretagogue). since chronic low-grade inflammation and islet inflammation have been linked to insulin resistance and beta-cell dysfunction in type diabetes, respectively, the 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patients association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. a new job for an old drug? the effectiveness of hydroxychloroquine in patients with type diabetes mellitus who are refractory to sulfonylureas--a randomized trial changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases efficacy and safety of hydroxychloroquine in the treatment of type diabetes mellitus: a double blind, randomized comparison with pioglitazone -p: effectiveness of hydroxychloroquine (hcq) mg in uncontrolled t d patients on dual therapy of metformin and sulfonylurea: a real-world experience in india expert group consensus opinion: role of anti-inflammatory agents in the management of type- diabetes rssdi clinical practice recommendations for the management of type diabetes mellitus hydroxychloroquine in diabetes and dyslipidaemia: primum non nocere drug approvals in india drug approvals in india -authors' reply the marketing of unproven drugs for diabetes and dyslipidaemia in india chloroquine stimulates glucose uptake and glycogen synthase in muscle cells through activation of akt mode of action of chloroquine in patients with non-insulin-dependent diabetes mellitus the clinical utility of c-peptide measurement in the care of patients with diabetes a practical review of c-peptide testing in diabetes insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats hydroxychloroquine improves insulin sensitivity in obese 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patient with systemic lupus erythematosus due to hydroxychloroquine considerations for drug interactions on qtc in exploratory covid- (coronavirus disease ) treatment. circulation guidance on minimizing risk of drug-induced ventricular arrhythmia during treatment of covid- : a statement from the canadian heart rhythm society cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of covid- patients: a scientific statement from the indian heart rhythm society is the type of diabetes treatment relevant to outcome of covid- ? risk of qt interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease assessment of qt intervals in a case series of patients with coronavirus disease (covid- ) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit coronavirus disease , and qt prolongation the long qt syndrome family 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antimalarial myopathy: an underdiagnosed complication? prospective longitudinal study of patients pearls & oy-sters: hydroxychloroquine-induced toxic myopathy mimics pompe disease: critical role of genetic test covid- infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose- -phosphate dehydrogenase deficiency glucose- -phosphate dehydrogenase deficiency and type diabetes examination of hydroxychloroquine use and hemolytic anemia in g pdh-deficient patients a pneumonia outbreak associated with a new coronavirus of probable bat origin covid- -navigating the uncharted observational study of hydroxychloroquine in hospitalized patients with covid- the urgency of care during the covid- pandemic -learning as we go type diabetes: demystifying the global epidemic global and regional diabetes prevalence estimates for and projections for and : results from the international diabetes federation diabetes atlas, covid- in critically ill patients in the seattle region -case series comorbidity and its impact on patients with covid- in china: a nationwide analysis clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study diabetes is a risk factor for the progression and prognosis of covid- prevalence and impact of diabetes among people infected with sars-cov- diabetes mellitus is associated with increased mortality and severity of disease in covid- pneumonia -a systematic review, meta-analysis, and metaregression accepted article endocrine and metabolic link to coronavirus infection covid- pandemic, corona viruses, and diabetes mellitus coronavirus infections and type diabetes-shared pathways with therapeutic implications role of adjunctive treatment strategies in covid- and a review of international and national clinical guidelines lombardy section italian society infectious and tropical diseases -. vademecum for the treatment of people with covid- no funding received. we would like to thank dr. nathalia padilla for her contribution to the comprehensive review of the literature. none declared. this article is protected by copyright. all rights reserved.accepted article key: cord- -fhkbcp z authors: hwang, yerin; khasag, altaisaikhan; jia, weiping; jenkins, alicia; huang, chien-ning; yabe, daisuke; kim, doo-man; kadowaki, takashi; lee, moon-kyu title: diabetes and covid- : idf perspective in the western pacific region date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: fhkbcp z abstract the world health organization (who) declared a pandemic, the highest risk level in the infectious disease alert phase, on march . in the western pacific region (wpr), , confirmed cases with , deaths had been reported as of june . in people with diabetes covid- can be more difficult to treat due to the wide fluctuations in blood glucose levels or presence of comorbidities such as diabetes complications, including cardiovascular disease and renal damage, which are recognized risks for adverse outcomes. national diabetes associations and governments have established guidelines for subjects with diabetes in relation to covid- , and are trying to supply emergency and their regularly required medical products for them. the wpr is so large and composed of such diverse countries and covid- situations, no one conclusion or program applies. instead we could see a diverse covid- pandemic profile in the wpr, and several creative diagnostic and therapeutic measures undertaken. this includes drive-through screening facilities, high-speed rt-pcr technologies, convalescent patients’ plasma therapy, which potentially had some positive contributions in combatting covid- in the wpr as well as globally. although the numbers of confirmed cases are currently decreasing in the region, the covid- pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of covid- . in january , a novel coronavirus ( -ncov, covid- ) from a cluster of pneumonia cases of unknown etiology was discovered in wuhan, china in people with diabetes covid- can be more difficult to treat due to wide fluctuations in blood glucose levels or presence of comorbidities such as acute and chronic diabetes complications, including cvd and renal disease, which even in the general population with covid- are recognized risk factors for poor outcomes, including death , , , . to mitigate covid- infection and poor outcomes many national diabetes associations and governments have established covid- guidelines for subjects with diabetes, and are trying to supply the emergency and routinely required medical products for them. the following is a summary of the current situation of each country in the western pacific region related to covid- . western pacific region (wpr) ) australia -in australia, as at june , there have been , positive cases and deaths. the first covid- positive case in australia was confirmed on january th in a person returning from wuhan china. this was followed by a lag phase with a doubling of positive cases approximately every - days. however, by march st , when covid- positive cases in australia exceeded , with deaths, australia was clearly on the exponential part of the curve . with introduced measures the number of new cases has substantially reduced since mid-april. since early may, daily testing nationally has ranged between , and , tests. details regarding diabetes status are not yet available. health personnel availability and support -reconfiguring wards-expanding or establishing new icus, with separate facilities for those with and without covid- : at no stage has there been a lack of ventilator facilities. -setting up separate inpatient covid- screening "hot" wards that were separate from "cold" wards -setting up special "fever" clinics, initially attached to a hospital but separate from other services, particularly emergency departments -novel screening pathways with initially more than less restrictive criteria for screening: an on-line self-registration and self-screening tool, drive-through screening and rapid throughput screening, to allow hospital workers with mild symptoms to be screened and get back to work in hours -securing adequate personal protective equipment (ppe), including from pre-existing national medical resources stockpiles and providing training on specialized techniques for urgent/safe gowning up -suspension of non-urgent surgery and procedures in both public and private hospitals with graded reintroduction -arrangements between state governments and private hospitals for the latter to take covid and non-covid patients, if and when required -upskilling and education of appropriate staff in best practice in procedures such as intubation to minimize risk to health professionals -call-up of, and short-term registration of, recently retired healthcare professionals and senior medical students -limitation or suspension of face-face non-urgent medical ambulatory or outpatient services (including outpatient adult and pediatric endocrinology/diabetes services), with a provision of telehealth services that would prevent emergency department presentations/admissions. newly diagnosed type diabetes patients were often still seen. -contact tracing those exposed to a person diagnosed with covid- , and planning, and subsequently implementing the covidsafe contact tracing app -fast-tracking of approval and implementation of covid- related research studies, with additional specific funding being made available by our national research funding agencies -implementing telephone/telehealth consultations for most endocrinology/diabetes services (including pediatric endocrinology) -the provision of inpatient diabetes education and medical review by telephone where possible for patients admitted with covid- to reduce exposure to essential diabetes staff , ) chinese mainland -china's goal in its medical response to covid- has been to improve the patient admission and cure rates and reduce the infection and fatality rates. a conditionspecific and category-based approach was applied to medical treatment of patients. pooling premium resources to treat severe cases. by directing resources to wuhan, china expanded the capacity of designated hospitals to deal with severe cases and increased the number of beds. two hospitals with , -plus beds each -huoshenshan and leishenshanwere built as specialist hospitals for treating infectious diseases, and a number of designated and general hospitals were expanded or remodeled. the number of beds for severe cases quickly increased from around , to more than , . early intervention for patients with mild symptoms. china has been quick to have patients with mild symptoms admitted to designated medical facilities for early medical intervention, and has done its best to prevent mild cases from worsening. the national clinical treatment network has been expanded to include more than , hospitals dedicated to the treatment of covid- patients. a national network of medical treatment coordination has also been formed to provide technical support through online consultation. in wuhan, faced with surging infections and considering that percent of cases were mild, the city government mobilized resources to repurpose stadiums and exhibition centers into temporary treatment centers. with some , beds, these centers were able to admit all confirmed mild cases for treatment. the treatment centers received a total of more than , patients; , and more were cured and discharged; and more than , were transferred to hospitals. temporary treatment centers, or fangcang shelter hospitals, are a major innovative solution that provided enough beds to admit all confirmed cases, thus turning the tide in the battle against covid- . based on scientific knowledge and accumulated evidence, research results and the diagnostic and therapeutic regimens that proved effective were incorporated in the national diagnosis and treatment plans. these include seven versions of the diagnosis and treatment protocol, three editions of the protocol for severe and critical cases, two editions of the manual for mild case management, two editions of convalescent plasma therapy treatment protocol, and one rehabilitation treatment program for patients discharged from hospitals . ) japan -since early april with the sharp increase in the number of covid- cases, the health care systems in japan has barely evaded collapse by ramping up the number of hospital beds dedicated to those with the disease (more than , beds nationwide) as well as by reallocating medical resources. that has accompanied postponing significant numbers of elective procedures and outpatient clinic visits. as of may th, , there are , total dedicated beds for covid- in facilities, and , mechanical ventilators. korea have been making tremendous efforts to prevent the spread of the virus. as many as hospitals have been designated as hospitals dedicated to covid- and over , beds in total have been made operative in preparation for a surge in cases. as the number of confirmed cases decrease, there was a stage-by-stage bed reduction to ultimately operate , - , beds, viewed as the lower limit for emergencies. aside from public hospitals, private medical centers are serving as main centers of treating patients with covid- . in addition, , medical staff were additionally allocated to support the hospitals, screening and treatment facilities. specifically, the korean government newly recruited and stationed public health doctors and army doctors, while continuing to recruit nurses. most of them were dispatched to daegu and gyeongsangbuk-do, which is the major epidemic region in korea. work was done to strengthen the monitoring and online reporting of cases identified at fever clinics of medical facilities. all such cases had to be reported online to higher authorities within hours; their test results sent back to the reporting clinics within hours; and on-site epidemiological investigation completed within hours -so that confirmed cases and asymptomatic carriers would be identified and reported without delay. as of may , a total of more than , close contacts had been traced and handled as appropriate. providing free treatment for patients. government funds for covid- control were made available in advance to ensure that patients could receive timely treatment and local authorities could proceed smoothly with measures for medical treatment and epidemic control. ) chinese mainland -all covid- patients, including those with diabetes, received subsidies from state finance for any medical bills not covered by basic medical insurance, serious disease insurance, or the medical assistance fund. these also cover the diabetic medication, including insulin support for patients. besides, urban and rural residents, ) hong kong -initially some patients with diabetes mellitus, they may have difficulty in sourcing alcohol swab, posing a challenge especially for those requiring insulin injections, in the initial period of covid- outbreak. however, the supply of disinfectant products was stabilized in a reasonable time frame. ) japan -although reduced, visits to clinics, hospitals, and pharmacies by those with diabetes had not been restricted in japan. likewise, distribution logistics in general has been constrained but maintained especially for medical supplies. although some hospitals and clinics reported a shortage of alcohol swabs used for insulin injections and/or finger-pricking for blood glucose testing, no major incidence of shortage has been reported for medical supplies for those with diabetes including insulin. this is partly aided by temporary lifting of restrictions on telemedicine, which had been only limitedly covered by japan's national care insurance. now, willing medical providers are able to send prescriptions and medical supplies to their patients by consulting over communication tools such as phone and video conference. continuity of medical care is relatively maintained by those means, but not ideally. for example, some diabetes specialists show concerns on patients' limited access to diabetes self-care education and support, which potentially deteriorates their glycemic control. we have some problems of insulin supply because borders are closed. the supply of insulin in taiwan is sufficient to cope with both emergency demand and usual care. perspectives in managing the pandemic in the country ) australia -it is recognized that that people with diabetes are at greater risk of serious outcomes during pandemics such as covid- than people without diabetes. it is anticipated that effective management of blood glucose in people with diabetes and covid- may lead to better outcomes and lower mortality rates. whether the resources that have been developed and measures that have been implemented have had a positive effect on the health of people with diabetes is not yet known. feedback from people with diabetes and health professionals has been positive and supportive of the proactive approach to this unprecedented pandemic. australian healthcare professionals and researchers are also proactive in proposing and participating in national and international covid- related research , . china has made vigorous efforts to resume work and reopen schools. since diabetic individuals might be susceptible to covid- infection, the following principles for covid- patients with comorbid diabetes were put forward by the chinese diabetes society (cds). for inpatients, blood glucose target should be individualized to minimize the risk for hypoglycemia after a careful evaluation. for out-patients, self-management of blood glucose and following doctors' advice are suggested . ) hong kong -outdoor activities have been restricted for all, which may have a negative impact on exercise. yet, people have cut down on dining as well, which may mean a healthier diet. although the widespread lockdown seen in many other countries has not been implemented in japan, a nationwide state of emergency was declared by the japanese government in the middle of april . this resulted in significant reduction of social and commercial activities in many sectors and it appeared that japan may have passed the current apex of infection rate as of early may. it is, however, difficult to predict whether this pandemic will end soon in japan and we are still undecided when and how to ease social and economic restrictions. the current transmission classification in the philippines is identified as clusters of cases with evidence of community transmission in highly urbanized areas (national capital region (ncr), cebu and davao). in spite of continued enhanced community quarantine in most affected regions in the country, several barangays (districts) are reporting a large increase in cases, resulting in local authorities to issue total lockdowns in these areas. over , covid- tests per day are being conducted by accredited laboratories throughout the country using pcr tests. no rapid antibody test kit has as yet been validated by the who or doh, so is not in use. and korean government are especially cautious when caring for patients who are vulnerable to this viral disease. subjects with diabetes are one of the top prioritized groups over any other chronic disease. the kda have announced recommendations for people with in this covid- outbreak. we will continue to do our best to prevent the spread covid- in korea and minimize deaths and complications related with covid- . taiwan -there have been no indigenous cases of covid- since april , , and the central epidemic command center (cecc) in taiwan will continue active surveillance and border control programs to prevent future outbreaks. meanwhile, the academic facilities in taiwan continue their work on improving laboratory diagnostic capacities, development of rapid testing, vaccination and antiviral agents. although the risk of community transmission of covid- in taiwan is very low, the pandemic has changed taiwanese ways of living and medical-seeking behaviors. how to track and educate patients with diabetes in taiwan, as well as providing necessary medical support and diet consultations has become challenging. we will develop individualized online education programs, and promote efficient data sharing between healthcare providers and patients via a national health insurance (nhi) medicloud system. the wpr is so large and composed of such diverse countries and covid- situations, no one conclusion can be developed. we see such diverse covid- pandemic profiles in the wpr, and several creative diagnostic and therapeutic measures have been implemented, such as drive-through screening facilities, high-speed rt-pcr testing technologies, convalescent patients' plasma therapy (which seems to show some benefit in the wpr and globally). although the numbers of confirmed cases are decreasing in the region, the war against the covid- pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of the covid- pandemic and for pandemics of other infectious agents in the future. a spirit of co-operation and knowledge sharing between countries and organizations is key to reduce the negative consequences of such infectious agents. world health organization, who western pacific regional action plan for response to large-scale community outbreaks of covid- covid- pandemic, coronaviruses, and diabetes mellitus clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study clinical characteristics of patients infected with sars-cov- in wuhan, china prevalence of comorbidities and its effects in patients infected with sars-cov- : a systematic review and meta-analysis the australian response to the covid- pandemic and diabetes -lessons learned fighting covid- china in action" released by the state council information office ofthe people's republic of china covid- , type diabetes clinical practice, research, and remote medical care: a view from the land down-under management suggestions for patients with diabetes and novel coronavirus pneumonia the authors declare no conflict of interest. the authors received no funding from an external source. key: cord- - jolt r authors: joensen, l. e.; madsen, k. p.; holm, l.; nielsen, k. a.; rod, m. h.; petersen, a. a.; rod, n. h.; willaing, i. title: diabetes and covid‐ : psychosocial consequences of the covid‐ pandemic in people with diabetes in denmark—what characterizes people with high levels of covid‐ ‐related worries? date: - - journal: diabet med doi: . /dme. sha: doc_id: cord_uid: jolt r aim: to map covid‐ ‐specific worries and overall psychosocial health among people with diabetes in the initial phase of the covid‐ pandemic in denmark, and to explore characteristics of people with diabetes and high levels of worries related to the covid‐ pandemic. methods: a cross‐sectional survey was conducted by distributing online questionnaires to adult members (> years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. the questionnaire included items on covid‐ ‐specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes‐specific social support, diabetes distress and changes in diabetes‐specific behaviours. responses were analysed with descriptive statistics and logistic regressions. results: people with diabetes have covid‐ ‐specific worries related to their diabetes. more than half were worried about being overly affected due to diabetes if infected with covid‐ , about one‐third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. logistic regressions showed that being female, having type diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about covid‐ and diabetes. conclusion: people with diabetes have covid‐ ‐specific worries related to their diabetes which is associated with poorer psychosocial health. these worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding covid‐ and diabetes. spread of coronavirus disease (covid- ) was declared a global pandemic by the world health organization (who) on march [ ] . for most people, covid- will cause only mild symptoms similar to a common cold, but it can also cause severe respiratory infections and multi-organ failure [ ] . the covid- outbreak started in in the hubei province, china in december . since then, the virus has spread rapidly to multiple countries across the globe within a very short space of time. in denmark, all schools and childcare services were closed on march, employees in the public sector with non-critical roles were sent home and a ban on gatherings of more than people was issued. care services were adapted to handle the covid- pandemic not only by increasing capacity to treat people with covid- , but also by avoiding spread of the virus between healthcare professionals and patients [ ] . the covid- outbreak and associated mass media coverage about the course of the pandemic worldwide and the frightening mortality levels in some countries are expected to increase the prevalence and change the character of psychological problems, including anxiety, depression and stress among citizens in affected countries [ ] [ ] [ ] . previous studies have highlighted the psychological impact of quarantine, which can cause post-traumatic stress symptoms, confusion and anger [ , ] . stressors related to quarantine include fear of infection, frustration, boredom, inadequate supplies, inadequate information, financial loss and stigma [ ] . during the covid- outbreak in china, a survey of respondents found that half rated the psychological impact of the outbreak as moderate or severe; % reported moderate to severe depressive symptoms; % reported moderate to severe anxiety symptoms; and % reported moderate to severe stress levels [ , ] . the study showed that people with chronic illness experienced greater stress, anxiety and depression compared with people without chronic illness [ ] . an increase in generalized fear has also been documented during other outbreaks such as sars in and spread of the ebola virus in [ ] . the psychological responses were particularly high among high-risk persons [ ] . it is well-established that diabetes under 'normal' conditions can have a significant and negative effect on quality of life. around % of people with diabetes experience diabetes distress as well as an increased prevalence of a range of psychosocial problems, including depression, anxiety, eating disorders and general stress compared with the general population [ , ] . the psychosocial consequences of the covid- pandemic may add to the burden of psychosocial problems of people with diabetes. the aim of this paper is: ( ) to map overall psychosocial health and covid- -specific worries among people with diabetes in the initial phase of the covid- pandemic in denmark; and ( ) to explore characteristics of people with high levels of worries related to the covid- pandemic. a cross-sectional survey was conducted by distributing online questionnaires to adult (> years) members of two user panels at steno diabetes center copenhagen and the danish diabetes association, respectively. the user panels consist of people with diabetes, who have volunteered to share information about their lives with diabetes. panels comprise people from all parts of denmark with type and type diabetes, latent autoimmune diabetes of adulthood (lada), gestational diabetes (gdm) and other rarer types of diabetes. thus, the panels represent people with diabetes who are treated in different primary and/or secondary care settings across denmark. invitations containing a link to the online questionnaire and written informed consent were sent to all members of the user panels via e-mail. the questionnaire was open for response seven days from the distribution date and a reminder was sent out if a response had not been recorded within the first three days. the study was approved by the danish data protection agency (p- - ). the questionnaire was developed in close collaboration with a person with diabetes and professional communication people working with patient involvement in diabetes care. this was done to ensure appropriate wording of normative items in the questionnaire to avoid inducing unnecessary worry or anxiety in the surveyed population. alongside with items on covid- -specific worries, the questionnaire included items on sociodemographic and health status, social relations, diabetes-specific social support, diabetes distress as well as changes in diabetes-specific behaviours. the generic mental health questions were developed as part of a larger danish data collection initiative 'standing together-at a distance: how danes are living with the corona crisis' (https://coronaminds.ku.dk/). the specific questions used in this study are listed in table s . items on covid- -specific worries included one question measuring general worries due to the covid- pandemic :'how worried are you about the corona-crisis on a scale from to ?', and a yes/no list of ten potential diabetesrelated worries due to the covid- pandemic. sociodemographic and health status items included age, gender, type of diabetes, complication status and latest hba c measurement as well as questions about whether the respondent had other chronic or mental illnesses. items regarding whether relatives or respondents themselves had experienced covid- symptoms or been diagnosed with covid- with or without hospitalization were also included. measures of social relations included general and diabetesspecific loneliness and diabetes-specific social support. general loneliness was measured with the three-item ucla loneliness scale [ , ] with response categories 'never/rarely', 'sometimes' what's new? • little is known about how worldwide pandemics affect the psychosocial health of people with diabetes. • this study showed a high prevalence of diabetesspecific worries related to covid- , especially fear of being overly affected by the virus, labelling of people with diabetes as a high-risk group, and inability to manage diabetes if infected. • female gender, type diabetes, diabetes complications, isolation, loneliness, high diabetes distress and behaviour changes were associated with being more worried about covid- and diabetes. • when providing information and support to people with diabetes in time of crisis, attention should be payed to crisis-specific worries in specific groups. and 'often', providing a total score from to . diabetes-related loneliness was measured with two questions developed for a previous qualitative pilot study [ ] and took the same format as the ucla loneliness scale. the questions measured: ( ) if the respondents missed someone to talk to about diabetes; and ( ) whether they felt alone with diabetes. the questions on loneliness were accompanied by a -to -point scale about the degree of feelings of isolation. diabetes-related social support from family, friends, people at work, healthcare professionals, other people in the community and people on social media was measured with questions inspired by the diabetes attitudes, wishes and needs (dawn) support for diabetes self-management profile [ ] . the original scale measures how supportive potential support providers are, with the response categories 'not supportive', 'somewhat supportive' and 'very supportive'. we also included social media as potential support which is not included in the original scale. the social support questions were analysed separately as single items in this study and not as a total score. diabetes distress was measured by the brief two-item diabetes distress scale (dds ) [ ] : 'feeling overwhelmed by the demands of living with diabetes' and 'feeling that i am often failing with my diabetes routine'. possible scores on each item range from (not a problem) to (a very serious problem). the dds score is derived as the average of the two items. a score > indicates moderate to high diabetes distress. changes in diabetes-related behaviours as a result of the covid- pandemic were measured with a yes/no list of potential behaviour changes related to diet, physical activity, medication taking and measurement of blood glucose. multivariate logistic regression models were used to examine the likelihood of experiencing: ( ) diabetes-related worries related to the covid- pandemic by sociodemographic factors and health status; and ( ) diabetes-related worries related to the covid- pandemic by sociodemographic factors, health status and psychosocial and behavioural factors. for each diabetes-related worry, the same base model consisting of age, gender, education, diabetes type and number of diabetes complications was used. in each regression, a specific explanatory psychosocial variable of interest was included. all coefficients were estimated using maximum likelihood and all coefficients are reported as odds ratios (or) with % confidence intervals (ci) and standard errors (se). p-values ≤ . were considered statistically significant. all analyses were performed in stata . (statacorp, college station, tx, usa) table shows sociodemographic and health status characteristics of the study population. half of the participants were women; age ranged from to years with a mean of years; almost half of the population had medium to higher tertiary education; % were employed; around one-third had type diabetes; % had diabetes complications; over covid- -specific diabetes worries figure shows that participants were most frequently worried about 'being overly affected due to diabetes if infected with covid- ' ( %), about 'people with diabetes being characterized as a risk group' ( %) and 'not being able to manage diabetes if infected with covid- ( %). in all, % were worried about 'possible lack of diabetes medications' and - % were worried about 'possible lack of diabetes equipment', 'reduced quality of professional health care during the covid- crisis' and 'insufficient access to health care professionals if needed'. in the later analyses, we focus on the three most prevalent worries. psychosocial health table presents levels of different psychosocial factors. mean rating of overall covid- -specific worries was . and mean rating of feeling socially isolated was . . one-quarter of participants had moderate to high diabetes distress (dds score > ). around %, % and % often or sometimes felt lonely, isolated from others and starved for company, respectively. the average loneliness score was . . roughly % often or sometimes felt alone with their diabetes, while % felt that they often or sometimes missed someone to talk to about diabetes. regarding diabetesspecific social support, most respondents ( %) received moderate to high levels of support from family, friends and people close to them. moderate to high support from people at work or school, diabetes care team, other people in the community and other people with diabetes, and people on social media ranged from~ % (people at work or school) to % (diabetes care team). characteristics of people with worries related to the covid- sociodemographic and health status were also more likely to be worried than those participants who did not experience diabetes loneliness. feelings of isolation also predicted being worried. participants who felt a stronger sense of isolation were more likely to experience worries (or . to . , % ci . to . ). changes in diabetes management due to the covid- pandemic participants who were more likely to have diabetes-related worries about the covid- pandemic were more likely to check blood glucose more often (or . to . , % ci . to . ), were more aware of medication taking (or . to . , % ci . to . ) and exercised more than usual (or . to . , % ci . to . ) ( table ) . eating more or less than usual were both associated with being worried about people with diabetes being characterized as a risk group compared with people eating as usual (or . , % ci . to . and . , . to . ). this study of people with diabetes showed that worries related to the covid- pandemic were highly prevalent. participants most frequently worried about 'being overly affected due to diabetes if infected with covid- ' ( %), that 'people with diabetes are characterized as a risk group' ( %) and 'not being able to manage diabetes if infected with covid- ' ( %). people with diabetes have been informed of the necessity to be acutely aware of the advice and restrictions imposed by the health authorities [ ] because they are expected to be at higher risk of being infected and to experience more severe symptoms of covid- if infected. the information from, for example, the danish health authorities varied in the initial phase of the pandemic: at first, people with diabetes were said to be at [ ] . the high morbidity and mortality in people with diabetes was made clear as well as the lack of knowledge about reasons for this. this information may potentially increase worries among people with diabetes and is likely to create a demand for more information. the question regarding worries about being labelled as a risk group was intended to measure experiences of stigma associated with this labelling. however, respondents may have interpreted this as being worried about the actual risk associated with diabetes. living with diabetes and managing the condition on a dayto-day basis are associated with heightened levels of anxiety and distress [ , ] . likewise, a range of different factors, such as sex, diabetes type and presence of complications, moderate the levels at which distress and anxiety are experienced [ , ] . in our population, % experienced diabetes distress at the beginning of the covid pandemic, which corresponds to what is found under normal circumstances [ ] [ ] [ ] . our findings also showed that experiencing high diabetes distress and feeling lonely were related to experiencing covid- specific worries. women, people with type diabetes and people with diabetes complications were more likely to express covid- worries than men, people with type diabetes and people without complications, respectively. this corresponds to previous findings of predictors for diabetes distress. [ , ] . we did not find an association between level of social support and covid- -specific worries, although previous studies have shown that a lack of social network and social support was associated with higher diabetes distress [ , ] . thus 'corona worries' seem to have resemblances to as well as differences from worries under normal circumstances. in , a survey of~ members of the danish diabetes association showed that loneliness is more frequent among people with diabetes and their relatives compared with the general danish population [ ] . in this population, % often or sometimes felt left out, % often or sometimes felt isolated from others, and % often or sometimes felt starved for company [ ] . in our study, the corresponding figures were, respectively, %, % and %. this indicates that a larger proportion of people with diabetes feel left out and starved for company during the covid- pandemic than during normal circumstances, but the proportion of people feeling isolated does not differ. people with diabetes are supposedly even more alone at home than the general population, which may lead to feelings of being left out and starved for company. the feeling of being left out may refer to not being able to, for example, take up what is allowed for the general population such as gathering up to people, which might not seem appropriate for people with diabetes, either by themselves or their friends and relatives. people feeling alone with or having no one to talk to about their diabetes were more than twice as likely to worry about covid- . qualitative studies show that people with diabetes under usual conditions experience a burden of feeling lonely with their diabetes [ ] . the present study showed that % often or sometimes felt alone with their diabetes, while % felt that they often or sometimes missed someone to talk to about diabetes. these are high numbers per se, and although we have not found valid information about usual conditions related to feeling lonely with diabetes, the frequency is expected to be higher under the covid- pandemic and the related isolation. our study indicates that people who report being more worried are more likely to check their blood glucose levels, are more aware of taking their medication and exercise more. this appears to be an upside and may be an adaptive response to the current situation. this behaviour may even relieve feelings of worry as exercise is associated with lower levels of, for example, stress, anxiety and depression [ ] . our results emphasize the need to communicate all new information regarding diabetes and covid- , as well as to provide support and guidance associated with specific and individual worries related to diabetes and covid- . more knowledge about how to provide this support systematically is needed. even under normal circumstances, it is often not possible for people with diabetes to get access to emotional support, but in the case of the covid- pandemic this might be even more important [ ] . peer support, social media and telephone support may be part of the solution [ , , ] . strengths of our study include the timeliness of the survey, which was initiated very shortly after substantial lockdown in denmark due to the covid- pandemic. the response rate of > % is considered relatively large under the circumstances, with a relatively short response time and only one reminder. also, the study included both people with type diabetes ( %) and type diabetes ( %). limitations include the convenience sample of participants, who may generally be healthier than the average person with diabetes. this is evinced by the relatively low prevalence of diabetes complications, for example retinopathy, with % in our study population reporting retinopathy compared with % in the danish diabetes registry [ ] . however, one could argue that our estimates are conservative given the fact that psychosocial issues are less pronounced in healthier individuals with diabetes, further emphasizing the gravity of the situation. furthermore, more than half of the population has at least one comorbid condition. all measures are selfreported, which may introduce uncertainties about prevalence of diabetes complications, comorbidity and glycaemic levels. validation of the questionnaire was somewhat compromised by time constraints imposed by the need to administer the survey as and when concerns about covid- were emerging. however, relevant actors from the danish diabetes association, the user-involvement programme at steno diabetes center copenhagen and a person with type diabetes contributed to and piloted the questionnaire through several iterations. very few respondents commented negatively about the questionnaire. this study highlights a high prevalence of worry among people with diabetes during the covid- pandemic related to being part of a high-risk group, as well as several other significant worries due to diabetes. further studies are needed to explore if and how covid- worries change during the pandemic. our study will be continued, and the future longitudinal study will contribute to this understanding. our findings are expected to be relevant in settings other than the danish, depending on the local course of the covid- pandemic and local restrictions. thus, our findings could be helpful in the effort to improve support for people with diabetes to manage their anxieties, particularly for those at greater risk of worries. providing peer support and support help lines may be helpful in mediating feelings of loneliness. none. none declared. who declares covid- a pandemic the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak diagnosis and clinical management of severe acute respiratory syndrome coronavirus (sars-cov- ) infection: an operational recommendation of peking union medical college hospital (v . ) -ncov epidemic: address mental health care to empower society the emotional impact of coronavirus -ncov (new coronavirus disease) the novel coronavirus (covid- ) outbreak: amplification of public health consequences by media exposure the psychological impact of quarantine and how to reduce it: rapid review of the evidence mental health strategies to combat the psychological impact of covid- beyond paranoia and panic immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china public mental health crisis during covid- pandemic diabetes distress in adults with type diabetes: prevalence, incidence and change over time psychosocial care for people with diabetes: a position statement of the american diabetes association a short scale for measuring loneliness in large surveys: results from two population-based studies reliability and validity of the danish version of the ucla loneliness scale the effect of peer support in adults with insulin pump-treated type diabetes: a pilot study of a flexible and participatory intervention diabetes attitudes, wishes and needs second study (dawn ): cross-national benchmarking of diabetes-related psychosocial outcomes for people with diabetes development of a brief diabetes distress screening instrument sundhedsstyrelsen: alle med diabetes er i risikogruppen [danish health authority: all people with diabetes are at risk addressing diabetes distress in clinical care: a practical guide the prevalence of diabetes-specific emotional distress in people with type diabetes: a systematic review and meta-analysis the detection and management of diabetes distress in people with type diabetes diabetes distress in type diabetes-a new measurement fit for purpose understanding the sources of diabetes distress in adults with type diabetes social support and self-management behaviour among patients with type diabetes en undersøgelse om ensomhed -ensomhed blandt mennesker med diabetes og p arørende til mennesker med diabetes [an investigation of loneliness -loneliness among people with diabetes and relatives to people with diabetes patient perspectives on peer support for adults with type diabetes: a need for diabetes-specific social capital diabetes prevention program research group. psychological predictors of physical activity in the diabetes prevention program if it does not significantly change hba c levels why should we waste time on it? a plea for the prioritization of psychological well-being in people with diabetes out-of-office hours nurse-driven acute telephone counselling service in a large diabetes outpatient clinic: a mixed methods evaluation the tinkering m-patient: co-constructing knowledge on how to live with type diabetes through facebook searching and sharing and offline tinkering with self-care dansk diabetes database we extend our sincere gratitude to the participants of this study for their invaluable responses to our questionnaire in a time of crisis, and to phd student astrid andrea schultz, dr tanja thybo and dr bryan cleal for valuable input to this study and paper. we would also like to acknowledge the entire 'standing togetherat a distance' team of researchers at the university of copenhagen for their cooperation in the conception of this study. additional supporting information may be found online in the supporting information section at the end of the article. table s . questionnaire content doc. s . english translation of the online article 'sundhedsstyrelsen: alle med diabetes er i risikogruppen' published on the website of the danish diabetes association, april . key: cord- - lhkiw p authors: gamble, anissa; pham, quynh; goyal, shivani; cafazzo, joseph a title: the challenges of covid- for people living with diabetes: considerations for digital health date: - - journal: jmir diabetes doi: . / sha: doc_id: cord_uid: lhkiw p the coronavirus disease (covid- ) is a global pandemic that significantly impacts people living with diabetes. diabetes-related factors of glycemic control, medication pharmacodynamics, and insulin access can impact the severity of a covid- infection. in this commentary, we explore how digital health can support the diabetes community through the pandemic. for those living with diabetes, digital health presents the opportunity to access care with greater convenience while not having to expose themselves to infection in an in-person clinic. digital diabetes apps can increase agency in self-care and produce clinically significant improvement in glycemic control through facilitating the capture of diabetes device data. however, the ability to share these data back to the clinic to inform virtual care and enhance diabetes coaching and guidance remains a challenge. in the end, it requires an unnecessarily high level of technical sophistication on the clinic’s part and on those living with diabetes to routinely use their diabetes device data in clinic visits, virtual or otherwise. as the world comes together to fight the covid- pandemic, close collaboration among the global diabetes community is critical to understand and manage the sustained impact of the pandemic on people living with diabetes. the coronavirus disease (covid- ) is a global pandemic and significantly impacts individuals living with diabetes. in china, wu and mcgoogan [ ] reported that people living with diabetes who contracted the virus had a more than triple mortality rate of % in comparison to % in those without diabetes. these figures align with previous global pandemics, which were also associated with increased morbidity and mortality in people with diabetes [ ] . during the h n pandemic, canadians living with diabetes had triple the risk of hospitalization and quadruple the risk of intensive care unit admissions [ ] . the severe acute respiratory syndrome epidemic also resulted in increased hospitalization and disease severity for people with diabetes [ , ] . as global pandemics continue to occur and the prevalence of diabetes increases [ ] , the diabetes community will be increasingly confronted with ongoing public health challenges [ ] . the world health organization has warned that older adults and those with pre-existing medical conditions like diabetes are at higher risk of covid- exposure, complications, and death [ ] . since the majority of the diabetes population are older [ ] and have multiple comorbidities of obesity, emphysema, hypertension, and heart failure [ , ] , they are at greater risk of viral infection. although data on covid- presentation has yet to support an increased risk of viral contraction in people living with diabetes [ , ] , evidence suggests that they may have worse outcomes should they contract the virus [ , ] . poor glycemic control is a significant contributor to covid- severity. hyperglycemic events can lead to diabetes ketoacidosis, which is a life-threatening condition that interferes with the immune response to mitigate sepsis and recovery [ ] . coronaviruses have also been shown to bind to their target cells through angiotensin converting enzyme- (ace ). fang et al [ ] proposed that the expression of ace is substantially increased in people managing their diabetes with ace inhibitors and antihyperglycemic angiotensin ii type-i receptor blockers [ ] . as such, these individuals may be at an increased risk of developing severe and fatal covid- . to maintain adequate glycemic control, people living with diabetes are normally encouraged to eat well, exercise, and maintain good mental health [ ] [ ] [ ] . however, efforts to minimize the risk of exposure to covid- have required social distancing and quarantine practices that may exacerbate insulin sensitivity through lower levels of physical activity, abrupt changes in social routine, poor dietary diversity, and diabetes distress [ ] [ ] [ ] [ ] . guidelines authored by prominent diabetes societies encourage the use of insulin as the preferred treatment during the global pandemic [ , ] . however, the impact of covid- on the global economy has compromised insulin production and access [ ] . for people who are insulin-dependent, the risk of an insulin shortage or delayed delivery is deadly [ ] . health professionals are recommending people to have a -day supply of diabetes medication and supplies for their medical devices [ ] . this advice may prove difficult to heed for the growing population of people in both urban ( . %) and rural ( . %) settings who experience socioeconomic disparities, specifically lower income, as they may not be able to afford adhering to such guidelines [ , , ] . in addition, the shortage of commercial antibacterial products may impede sterilization techniques for insulin injections and blood glucose monitoring, and promote infection [ ] . significant decreases in traditional in-person clinic availability will require people to adopt and adjust to receiving digital diabetes care [ ] . in response to social distancing guidance, outpatient diabetes clinics and family medicine practices have greatly curtailed their services to only the most urgent cases [ ] . even as restrictions are expected to ease over time, there will be continued caution in visiting clinics. in light of these circumstances, the use of previously restricted forms of communication between providers and their patients have been allowed. most forms of audio, video, or texting technology have been allowed by jurisdictions through not only relaxing privacy and security requirements but also reimbursing providers for these services. even telephone calls have become an accepted modality for conducting a clinical visit, allowing those without sophisticated consumer devices like smartphones to access services [ ] [ ] [ ] . for those living with diabetes, this is an opportunity to be able to access care with greater convenience while not having to expose themselves to infection in an in-person clinic. if the use of virtual visits continues after the pandemic eases-as they are expected to [ ] -it opens up a great opportunity to provide more timely access to not only physician care but services that are often scarce for those living with diabetes [ ] . with physical distances no longer a factor, virtualizing the care provided by diabetes educators, dieticians, and specialized mental health professionals could improve access further than what was previously possible with in-person encounters [ ] . these successes can only be realized if broader digital health inequities of access and literacy are addressed within the diabetes community [ ] . perhaps more compelling than improving access to health services through virtual care, digital health apps can also create greater agency in self-care. a series of studies in recent years have demonstrated that diabetes smartphone apps with the ability to capture diabetes data and other self-reported factors can produce clinically significant improvement in glycemic control for both those living with type diabetes and type diabetes [ , , ] . these outcomes were achieved without the benefit of a provider facilitating care through the app. additional studies have since shown that outcomes can be further enhanced with the addition of virtual care and the active use of diabetes data sharing to enhance diabetes coaching and guidance [ , ] . despite the positive enablers for remote diabetes care, the ability to share diabetes device data back to the clinic remains a challenge [ ] . as it stands, the current landscape of diabetes device data interoperability is a patchwork of proprietary technologies, open source tools, and restrictive electronic health record (ehr) policies. in the end, it requires an unnecessarily high level of technical sophistication on the clinic's part and on those living with diabetes to routinely use their diabetes device data in clinic visits, virtual or otherwise [ ] [ ] [ ] . this technical burden will simply continue to hamper efforts to facilitate comprehensive virtual care. it continues to be a challenge to convince manufacturers of diabetes devices and ehr vendors to create truly interoperable systems to ease the burden on the diabetes communities [ ] . it is hoped that the pandemic further reveals the flaws of the industry's business tactics to maintain exclusivity and their slow response in addressing the needs of the diabetes community. as the world comes together to fight the covid- pandemic, close collaboration among the global diabetes community is critical to understand and manage the sustained impact of the pandemic on people living with diabetes. figure presents a summary of the challenges of covid- for people living with diabetes and the opportunities of diabetes digital health to support them in this time of need. contribution and access to trusted diabetes resources that can communicate actionable insights on the status of covid- are needed to support the community through these challenging times [ , , [ ] [ ] [ ] [ ] [ ] [ ] . characteristics 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self-management: a systematic review of randomized controlled trials to identify functions associated with glycemic efficacy effectiveness of mhealth interventions for patients with diabetes: an overview of systematic reviews overcoming clinical inertia: a randomized clinical trial of a telehealth remote monitoring intervention using paired glucose testing in adults with type diabetes telemedicine in complex diabetes management why download data: the benefits and challenges of more diabetes data a minority of patients with type diabetes routinely downloads and retrospectively reviews device data a case study in open source innovation: developing the tidepool platform for interoperability in type diabetes management digital diabetes self-management: a trilateral serial keeping our diabetes community healthy covid- update from lmc url what you need to know about diabetes and the coronavirus url coronavirus and t d: what you need to know and how to prepare figure . the challenges of covid- for people living with diabetes and the opportunities of diabetes digital health. none declared. . . . this is an open-access article distributed under the terms of the creative commons attribution license (https://creativecommons.org/licenses/by/ . /), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in jmir diabetes, is properly cited. the complete bibliographic information, a link to the original publication on http://diabetes.jmir.org/, as well as this copyright and license information must be included. key: cord- - ovdnxl authors: dunachie, susanna; chamnan, parinya title: the double burden of diabetes and global infection in low and middle-income countries date: - - journal: trans r soc trop med hyg doi: . /trstmh/try sha: doc_id: cord_uid: ovdnxl four out of five people in the world with diabetes now live in low- and middle-income countries (lmic), and the incidence of diabetes is accelerating in poorer communities. diabetes increases susceptibility to infection and worsens outcomes for some of the world’s major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. there is some evidence that chronic viral infections such as hepatitis b and hiv may predispose to the development of type diabetes by chronic inflammatory and immunometabolic mechanisms. helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. a greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in lmic is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. this review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection. there are now million people with diabetes living in low-and middle-income countries (lmic). , diabetes increases susceptibility to infection and worsens outcomes for diseases such as tuberculosis (tb), and the under-recognised tropical disease melioidosis. , current international treatment guidelines for diabetes are based on research conducted in high-income countries focussed on preventing adverse cardiovascular outcomes and early death. there is a lack of evidence upon which to base guidelines for people living in lmic, where there is an increased burden of infectious diseases compared with high income countries. diabetes has traditionally been viewed as a 'disease of the wealthy', mostly found among elderly people in developed countries. now, however, diabetes affects every strata of society, and has become a fast-growing problem in poorer communities. the global burden of disease (gbd) study estimated there were . million deaths worldwide from diabetes in , representing a % increase from . of the estimated million people with diabetes worldwide, four-fifths currently live in lmic and increasing numbers of children and young adults have been diagnosed with the disease. this number is projected to increase to million by , and most of the rising burden will occur in lmic ( figure ). in addition, diabetes is more likely to be undiagnosed or poorly treated in lmic. data from the ncd risk factor collaboration show that agestandardised diabetes prevalence in adults has increased or remained unchanged since in every country. importantly, the burden of diabetes has increased faster in lmic than in high-income countries. this rising prevalence of diabetes in lmic is believed to be associated with many factors, including ageing populations, urbanisation, cultural and social changes, dietary changes, physical inactivity, changes in diagnostic criteria and screening practices, better treatment and survival, and increasing trends in overweight and obesity. classification of diabetes table shows the current classification of diabetes by who and the american diabetes association (ada), , which includes four clinical and aetiological classes: type diabetes (t dm), type diabetes (t dm), gestational diabetes mellitus, and other specific types of diabetes due to other causes. t dm is caused by an autoimmune reaction which destroys the insulin-producing beta cells in the islets of the pancreas, leading to no or low production of insulin. t dm is the most common type of diabetes, accounting for approximately % of all cases of diabetes worldwide. it is characterised by an inadequate production of insulin and an inability of the body to respond fully to insulin, defined as insulin resistance. it is important to note that assigning a type of diabetes to an individual is often reliant on the circumstances present and additional testing at the time of diagnosis, and that many patients with diabetes do not easily fit into a single class. in lmic, it is often unknown which type of diabetes a person has, and therefore this review will use the general term 'diabetes', but > % of patients with diabetes in lmic are believed to have t dm. table summarises the modifiable and non-modifiable risk factors for t dm, which is a disease caused by a complex interplay between genetic and environmental factors. the rapid increase in the prevalence of diabetes over recent decades suggests that environmental and lifestyle factors might play an increasingly important role in the development of the disease. it is generally recognised that people with diabetes are at increased risk of infection and worse outcomes, , including diabetic foot infection, urinary tract infections (especially from tuberculosis (tb) is a leading cause of disease and death worldwide, with an estimated million cases of tb and . million deaths in . diabetes is associated with a threefold increased risk of developing tb, and increased risk of death or treatment failure in tb. the gbd group reported diabetes accounting for . % of the tb mortality in hiv-negative people. in , cases of tb were attributable to diabetes, and the absolute numbers of people with tb-diabetes co-morbidity is now similar to people with tb-hiv co-infection. more than half of the world's tb cases occur in five countries, which have significant prevalence rates and total numbers of diabetes cases in adults aged - years as follows: china ( . %, million), india ( . %, million), indonesia ( . %, million), philippines ( . %, . million) and pakistan ( . %, . million). there is evidence that the presence of clinical tb disease drives stress hyperglycaemia, impacting on clinical outcomes and response to treatment. as rates of diabetes continue to rise, and the tb epidemic continues, there is a pressing need for bidirectional screening in countries facing the double burden of tb and diabetes. work in india has shown success at screening newly diagnosed tb cases for diabetes, due to the availability of a simple screening blood test (hba c) and the use of existing systems established to screen tb cases for hiv. screening people with diabetes for tb is more difficult due to the reliance on symptom questionnaires followed by chest xray. a blood test to diagnose tb in this setting is highly desirable, but current interferon gamma release assays (igras) do not have sufficient sensitivity and specificity for this purpose. diabetes is also associated with higher rates of mycobacterium leprae. , the greatest increased risk for infection in people with diabetes is seen for the grossly under-recognised tropical disease melioidosis, which is caused by the gram-negative bacterium burkholderia pseudomallei. people with diabetes have a twelvefold increased risk of melioidosis, and over half of all cases of melioidosis have diabetes. b. pseudomallei is an environmental saprophyte with a predilection for rice paddy fields, and melioidosis is typically seen in adults in middle age and above, often in rice-farming communities. a broad range of clinical presentations are seen, including pneumonia, acute sepsis with bacteraemia, abscess formation in any organ site, chronic subacute disease and latency. , transmission of the bacterium to humans occurs via three routes: inhalational, cutaneous via skin abrasions and ingestion of contaminated drinking water. the disease is commonly diagnosed in southeast asia and northern australia, but is now known to be present in countries across tropical regions, with an estimated annual cases and deaths. if rates of diabetes continue to rise as predicted, coupled with an increased reliance on older people for rice farming due to exodus of the younger generation to urban areas, then the burden of melioidosis will also rise. studies in high-income countries have shown that people with diabetes have high rates of infection from many common bacteria, but some bacterial species are more frequently reported in association with diabetes. diabetes is an established risk factor for invasive infection with staphylococcus aureus. s. aureus is the commonest cause of tropical pyomyositis, an infection of skeletal muscle featuring intramuscular abscesses that is commonly seen in tropical regions and can account for - % of acute admissions. pyomyositis occurs less frequently in temperate zones, where diabetes is a known risk factor. , while diabetes has been reported in some case reports of tropical pyomyositis, further research is needed to establish the box . relationship between diabetes and susceptibility/increased disease severity for significant pathogens in low-and middle-income countries. see text for discussion of evidence. diabetes was associated with around a threefold increased risk of infection with s. enteritidis following exposure in a us hospital outbreak. people with diabetes have an increased risk of klebsiella infections, especially klebsiella liver abscess in asia. , scrub typhus is a febrile illness caused by the rickettsial group intracellular pathogen orientia tsutsugamushi. around a million cases a year occur in asia, and it is believed to exist in other tropical regions outside asia. diabetes was an independent risk factor for more severe disease in a prospective study of eschar-positive scrub typhus. it remains to be established why diabetes confers much greater susceptibility to, and worse outcomes for some bacteria than to others. several of the bacteria most closely associated with diabetes, such as m. tuberculosis and b. pseudomallei, are predominantly intracellular bacteria. impairments in phagocyte function and adaptive t cell immunity in diabetes may contribute to increased susceptibility to intracellular pathogens. diabetes is associated with antimicrobial resistance (amr). diabetes status is associated with increased rates of drug resistance in tb, including multidrug-resistant tb. , besides tb, people with diabetes are over-represented in cohorts with multi-drugresistant infections, but there is a lack of evidence at present of higher rates of amr in bacterial isolates from people with diabetes compared with isolates from non-diabetics. what is clear is that increasing rates of amr will have a larger impact on people with diabetes, due to their higher risk of infection and increased need for healthcare exposure and interventions. dengue causes an estimated million clinical cases per year and deaths. an association between diabetes and severe presentations of dengue is now broadly accepted. however, studies are typically retrospective, often small in nature, and use varying definitions of severe dengue. in a metaanalysis of five case-control studies of acute dengue, diabetes was associated with an increased risk of a severe clinical presentation of dengue compared with either asymptomatic infection or non-severe acute dengue, although given the limited data, the authors emphasised this was only suggestive of a link. this finding has been supported by further studies in malaysia and china. a systematic review to evaluate the contribution of non-communicable diseases (ncds) to the development of severe dengue identified relevant publications and gives a clear overview of this literature, but given the heterogeneity of the studies the authors concluded that the existing literature was inadequate for meaningful estimation of the impact of diabetes and other ncds on dengue severity. the following year a canadian group reported a nearly three-fold higher prevalence of diabetes in patients in studies with severe dengue than the prevalence of diabetes in subjects in studies with non-severe dengue. the same analysis found hypertension, heart disease and obesity (conditions interrelated with diabetes) to be significantly more prevalent in severe dengue, and also reported a four-fold increased prevalence of diabetes in severe west nile fever cases by the same methodology, supporting an earlier study . the authors acknowledge the multiple limitations of this approach, including the heterogeneity of the studies and publication bias for studies included. there is clearly a need for further high-quality epidemiological studies to further define the association. there is some evidence that diabetes is associated with more severe disease in chikungunya disease, but there is a current lack of data for analysing the relationship with zika virus. other viral infections may be associated with diabetes. people with diabetes are an at-risk group for clinical illness, disease severity and death from influenza, with a meta-analysis of articles showing diabetes to be a risk factor for death from pandemic influenza (predominantly h n ), although there was a lack of high-quality cohort studies to demonstrate this in seasonal influenza. it is estimated that million people are chronic carriers of the hepatitis b virus (hbv), and hbv has recently been described as a neglected tropical disease. a number of studies have shown a higher prevalence of hbv in people with diabetes, [ ] [ ] [ ] and people with chronic hbv are reported to have an increased risk of developing diabetes, although this has not been demonstrated to date in sub-saharan africa. , in addition, diabetes is associated with disease progression of hbv, - which has also been reported for hepatitis c. varicella zoster virus (vzv) causes chickenpox as a primary infection which can reactivate as herpes-zoster (shingles), especially in older people. diabetes is an established risk factor for shingles. , diabetes is considered a risk factor for middle east respiratory syndrome (mers). a recent systematic review identified published works for analysis, with several reporting diabetes as a risk factor for infection and death, but meta-analysis to quantitate the increased risk of diabetes across the studies was not possible due to the small number of studies addressing this risk factor. people living with hiv (plhiv) who receive combined antiretroviral therapy (art) now have excellent long-term survival, but increased rates of metabolic disorders such as impaired glucose tolerance, hyperlipidaemia and body morphological changes (lipodystrophy syndrome) have been reported. increased rates of insulin resistance in plhiv could occur due to the proinflammatory effects of chronic viral infection, direct effects of art, and also indirect effects of art such as dyslipidaemia and body fat distribution changes. although studies in high-income western countries have shown inconsistent results as to whether hiv infection increases the risk of t dm or merely represents earlier diagnosis in a closely monitored population, there is evidence that hiv increases the risk of diabetes in asian and african populations. a study in taiwan suggested plhiv to be as much as sixfold more likely to develop diabetes than the rest of the population, and a recent thai study of plhiv showed diabetes developed at a younger age compared with the general population. increased rates of diabetes have also been reported in plhiv in south africa, tanzania and ethiopia. older art drugs such as stavudine and zidovudine are known to increase the risk of metabolic syndrome and diabetes, and are used less now, so future studies may not confirm this relationship. parasitic malaria remains one of the world's largest causes of mortality from infectious diseases, with an estimated million cases and deaths per annum. in , researchers reported a % increased risk of malaria in people with diabetes in a case-control study in an urban setting in ghana. the malaria was predominantly p. falciparum, asymptomatic and diagnosed by pcr. the comparison of probability of malaria infection was made between patients with diabetes (n= ) and a control group (n= ) comprising patients attending hypertension clinics, patients attending other hospital clinics, and hospital staff. the groups were not matched in that the diabetes group were older by a mean of . years and had a socio-economic profile associated with greater poverty, and the adjusted odds ratio for diabetes as a risk factor for p. falciparum infection was just outside significance in a multivariate analysis adjusting for these parameters (adjusted or . , % ci . - . ). this report is very interesting, but there have been no further published clinical studies addressing the relationship between diabetes and malaria. if diabetes increases the risk of malaria this would be of huge significance on a global scale. as india is a country with a high burden of both diabetes and p. vivax malaria, one might expect evidence of a relationship between diabetes and vivax malaria to emerge from research in this region. further prospective studies with well-matched cohorts, and research into the effect on outcomes for people with malaria is needed. diabetes has been linked to increased risk of cutaneous , and visceral leishmaniasis, and diabetes and hyperglycaemia were more frequently reported in cardiomyopathy caused by trypanosoma cruzi (chagas disease) than in controls. there are a lack of data on the relationship between diabetes and most neglected tropical diseases (reviewed ) and prospective studies of people with diabetes in tropical regions are needed to evaluate this. some interesting findings have been reported for a lower risk of diabetes following helminth infections including schistosomiasis, strongyloides and filariasis, as reviewed by berbudi and colleagues. the mechanism for such a protective effect could be by helminth infection inducing a shift towards type (anti-inflammatory) immune responses, and reducing chronic low-grade inflammation. a mouse model demonstrated greater insulin sensitivity following s. mansoni infection in mice fed a high-fat diet, with an increase in type cytokines and the ratio of m to m macrophages in white adipose tissue. further research is evaluating whether helminth-derived molecules could be developed as novel therapeutic approaches to diabetes and metabolic syndrome. in addition, a prospective randomised-control trial of helminth eradiation by albendazole therapy in indonesia is underway evaluating the impact of helminth infections on insulin resistance. the mechanisms by which diabetes confers altered susceptibility to infections are likely to be via multiple effects on the human immune system. people with diabetes have altered skin flora, including increased colonisation with s. aureus. breaches in the skin's integrity as a physical barrier to infection occur more commonly in diabetes due to the impact of chronic hyperglycaemia on peripheral nerves and vascular supply. diabetes and its treatment has an impact on the composition of the gut microbiome, and the pivotal role of the gut microbiome in modulating human innate and adaptive responses via pathogen recognition receptor pathways and secretion of immunomodulatory molecules by gut bacteria is now emerging. in vitro, mild hyperglycaemia may favour pathogen growth, and while the contribution of this to human susceptibility to infection is unknown, glycosuria favours urinary tract infections. in addition, hyperglycaemia has a number of immunosuppressive effects, including impairment of neutrophil degranulation, complement activation and phagocytosis. hyperglycaemia does not, however, appear to be a key mechanism for the increased susceptibility to tb. diabetes is associated with endothelial dysfunction, oxidative stress and chronic inflammation. in infections like dengue, this may support a shift towards an excessive pro-inflammatory response, leading to the cytokine storm, shock, vasculopathy and coagulopathy that feature in severe dengue. finally, people with diabetes have higher rates of hospital admissions, which exposes them to hospital-acquired infections and the risk of amr. there is overlap between the spectrum of pathogens that people with diabetes have, notably increased susceptibility to such as s. aureus and invasive fungi, and the infections seen in chronic granulomatous disease (cgd), which is congenital deficiency in phagocytic function. this suggests impairment of neutrophil and macrophage function in people with diabetes as a key mechanism of susceptibility. this is supported by studies showing impaired neutrophil migration, phagocytosis and intracellular killing in the host response to b. pseudomallei in people with diabetes. however, people with cgd are not known to have increased susceptibility to viral infections, and therefore this impairment of phagocyte function is unlikely to be the only cause of increased susceptibility to infection in diabetes. the literature on humeral responses to infection in people with diabetes does not suggest that poor antibody response is a dominant mechanism for the increased susceptibility to infection seen in diabetes. most studies support adequate induction of antibodies in response to licenced antibody-inducing vaccines in people with diabetes [ ] [ ] [ ] . higher antibody responses to influenza vaccine were seen in a us study of elderly people with diabetes compared with elderly non-diabetic people, and antibodies induced by natural exposure to melioidosis were higher in those with diabetes. such higher responses in diabetes could be due to chronic hyperactivation of the innate immune response in t dm resulting in polyclonal b-cell stimulation and enhanced antibody production to stimuli. beyond neutrophil changes, people with diabetes have alterations in the function of several cell types including macrophages, s. dunachie and p. chamnan natural killer cells, cd t cells and cd t cells function. t cell responses are known to be important in host defence against intracellular pathogens, with intracellular antigens presented to cd t cells via the mhc class antigen presentation pathway, and digested antigens from both extracellular and intracellular sources presented to cd t cells via the mhc class system. hiv results in reduction of cd t cells, and the huge increased risk of tb seen in advanced hiv demonstrates the importance of cd cells in defence against tb. there is evidence of impaired antigenspecific t cell responses in people with diabetes in response to early tb , b. pseudomallei and vzv , although in established tb the cellular response appears to be higher in diabetes. in addition, differences in the regulation and orchestration of the immune response are seen in dengue. for further detailed discussion of immune mechanisms, the reader is referred to a number of excellent reviews of immune impairment in diabetes. , overall, diabetes can impair the immune system at a systemic, cellular and molecular level, but it is the alteration of t cell function that is most amenable to boosting with targeted vaccination strategies. acute infection is known to lead to hyperglycaemia as a consequence of the stress-response activation of the hypothalamicpituitary-adrenal axis to increase secretion of cortisol and other hormones which promote peripheral insulin resistance, alongside alteration of insulin-receptor signalling by pro-inflammatory cytokines (reviewed ). sepsis-related hyperglycaemia may be a risk factor for future development of t dm, and stress hyperglycaemia induced by chronic infections such as tb may contribute to the global burden of diabetes. concerted international efforts to stem the tide of advancing diabetes in lmic are urgently required. implementation of evidencebased approaches that are effective at both prevention and early intervention for diabetes are needed. such approaches require behavioural changes in diet and physical inactivity, raising public awareness of diabetes, and convincing policy-makers and the public alike of the benefits of early diagnosis for disease reversal and management. one of the targets for the un's sustainable development goal (good health and well-being) is to reduce by one-third premature mortality from ncds through prevention and treatment by , with action on diabetes essential. actions include implementation of national diabetes programmes and extension of health promotion activities. tackling the interaction between diabetes and infection requires a greater understanding of the immune mechanisms underlying the altered susceptibility to infection seen in diabetes, and knowledge of how therapeutic management of diabetes impacts on risk of infection. it is likely that tight control of hyperglycaemia lowers the risk of infection, although this has yet to be comprehensively demonstrated in prospective studies. current international treatment guidelines for t dm are based on research conducted in high-income countries focussed on preventing adverse cardiovascular outcomes and early death. there is a lack of evidence on which to base guidelines for people living in lmic, and choice of glucose-lowering therapy may impact on infection risk and outcomes. for example, there is emerging evidence for beneficial infection outcomes in people with diabetes taking metformin compared with other therapies, [ ] [ ] [ ] and glyburide/glibenclamide has been associated with anti-inflammatory properties and lower mortality in melioidosis. vaccination remains the cornerstone in controlling infectious diseases, and people with diabetes are prioritised as a high-risk group for vaccination against a range of pathogens including pneumococcus, influenza and vzv. development of highly efficacious vaccines against intracellular infections such as tb, melioidosis and leishmaniasis, to which people with diabetes are at greater risk, is an important priority, and progress requires consideration of how to overcome the specific immune impairments seen in diabetes. characterising the impact of diabetes on protective immunity is particularly important for melioidosis, where more than half of all cases occur in people with diabetes, and cost-effective implementation of a successful vaccine is likely to involve targeting this group. b. pseudomallei therefore represents an exemplar pathogen for defining the immune deficits in diabetes, and how to overcome them. the collision of diabetes and the world's global infections is a highly neglected area. more research to clearly define the epidemiology and illuminate successful interventions needs prioritising. the majority of the evidence for associations between diabetes and specific infections relies on the use of relatively small retrospective case-control studies, and meta-analysis approaches are limited by the heterogeneity of patient-level factors across studies. diabetes is interrelated with obesity, hypertension and cardiovascular diseases that share similar risk factors and are each linked to adverse disease outcomes, rendering elucidation of the precise contribution of diabetes to excess morbidity and mortality difficult. the causal interaction between diabetes and infection rates and outcomes is also challenging. for some chronic viruses such as hbv and hiv, the association with diabetes may represent increased risk of diabetes by pathogenesis mechanisms resulting in insulin resistance related to chronic inflammation, rather than the other way around. high-quality, large prospective epidemiology studies are needed to quantitate the problem, alongside randomised controlled trials of interventions to define optimal treatment strategies in diabetes. raising awareness of the interaction of diabetes and infection with policy-makers, and ensuring the engagement of social scientists, health economists and the pharmaceutical industry in developing new strategies to fight this double burden in lmic is vital. authors' contributions: sd and pc wrote and reviewed the manuscript together. 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colony-stimulating factor by type diabetes' mononuclear cells infected with dengue virus, but not increased intracellular viral multiplication the impact of diabetes on the pathogenesis of sepsis hyperglycemia in sepsis is a risk factor for development of type ii diabetes metformin and other glucoselowering drug initiation and rates of community-based antibiotic use and hospital-treated infections in patients with type diabetes: a danish nationwide population-based cohort study metformin as adjunct antituberculosis therapy metformin use and severe dengue in diabetic adults glyburide is antiinflammatory and associated with reduced mortality in melioidosis melioidosis vaccines: a systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes acknowledgements: none. ethical approval: not required. key: cord- -ef i bo authors: sciberras, justine; camilleri, lara maria; cuschieri, sarah title: the burden of type diabetes pre-and during the covid- pandemic – a review date: - - journal: j diabetes metab disord doi: . /s - - - sha: doc_id: cord_uid: ef i bo introduction: diabetes mellitus is a chronic disease and a global epidemic. it is a known fact that co-morbidities, including diabetes mellitus, pose a higher risk of infection by covid- . additionally, the outcomes following infection are far worse than in people without such co-morbities. factors contributing to the development of type diabetes mellitus (t dm) have long been established, yet this disease still bestows a substantial global burden. the aim was to provide a comprehensive review of the burden of diabetes pre-covid- and the additional impact sustained by the diabetes population and healthcare systems during the covid- pandemic, while providing recommendations of how this burden can be subsided. methodology: literature searches were carried out on ‘google scholar’ and ‘pubmed’ to identify relevant articles for the scope of this review. information was also collected from reliable sources such as the world health organisation and the international diabetes federation. results: t dm presented with economic, social and health burdens prior to covid- with an significant ‘disability adjusted life years’ impact. whilst people with diabetes are more susceptible to covid- , enforcing lockdown regulations set by the public health department to reduce risk of infection brought about its own challenges to t dm management. through recommendations and adapting to new methods of management such as telehealth, these challenges and potential consequences of mismanagement are kept to a minimum whilst safeguarding the healthcare system. conclusion: by understanding the challenges and burdens faced by this population both evident pre-covid and during, targeted healthcare can be provided during the covid- pandemic. furthermore, implementation of targeted action plans and recommendations ensures the care provided is done in a safe and effective environment. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. diabetes mellitus is a chronic disease resulting from the reduction in the body's response to insulin production by the pancreas either due to an increase in insulin resistance or due to decreased insulin production [ ] . in the past three decades, incidence of diabetes has quadrupled worldwide [ ] . diabetes has also classified as the th leading cause of death globally in [ ] . according to the recent data published by the international diabetes federation, million adults ( - years) suffered from diabetes in . if not adequately controlled, the global diabetes prevalence is expected to increase by approximately % in [ ] . the contributing factors for the development of type diabetes (t dm) can be broadly divided into genetic and environmental factors. electronic supplementary material the online version of this article (https://doi.org/ . /s - - - ) contains supplementary material, which is available to authorized users. some specific risk factors include, obesity, smoking, leading a sedentary lifestyle, age and also the presence of metabolic syndrome [ , ] . the pathophysiology and the underlying risk factors have long been established, yet the incidence of diabetes is still on a progressive incline [ ] the coronavirus sars-cov pandemic has further increased the burden on the diabetes population, those at risk of dyglcyaemic changes as well as the healthcare services [ ] . the aim of this article was to provide a comprehensive review of the burden of diabetes pre-covid- and the additional impact sustained by the diabetes population and healthcare systems during the covid- pandemic, while providing recommendations of how this burden can be subsided. a literature search was carried out in july through 'pubmed' and 'google scholar' using the keywords 't dm', 'covid- ' and 'public health'. articles were then filtered using several inclusion criteria including; english language, human studies and literature type. the latter mainly included systematic reviews, meta-analysis and literature reviews. the authors then filtered the resulting articles by title and abstract and the remaining articles which fitted the aim of this review were thus considered. additionally, information was also collected from reliable reports such as those of the world health organization (who) and international diabetes federation (idf). having an understanding of the impact of t dm at an individual, community and population level is paramount for public health authorities and policymakers alike. the burden of a disease can be quantified in terms of the quality of life, morbidity, premature mortality, economic and healthcare impact [ ] . public health policies and plans for provision of services all depend on the general population's state of health and comorbid diseases which change over time. developed in the s, the dalys metric is used to gauge the total burden of a disease by considering the number of years lost to a disease, premature mortality, or disability. it is also used to compare health and life expectancy globally. such a calculation gives policy makers a better understanding of the overall duration of life in comparison to duration spent in poor or good health [ ] . a global observation of the incline in dalys across years comparing individuals at different age categories ( - years, - years vs + years) adapted from the global burden of disease website can be seen in figs. , and respectively. [ ] . as seen in the graphs, the higher incidence of t dm at a younger age range is contributing to the increase in dalys. this will place a strain on healthcare costs and economic healthcare services as well as [ ] decreased work productivity and increased likelihood of early retirement or mortality. this will ultimately be a burden on the country's economy. the universal rise in life expectancy has left policy makers questioning whether individuals maintain a good quality of life during these additional years, as reported by the global burden of disease (gbd) study and illustrated in figs. , and . such evaluations are extremely relevant to decisions involving extension of retirement ages and health care stipulations. namely to increase efforts for risk prevention of non-communicable diseases such as t dm from early stage of the disease. great inequalities between the burden of a disease and healthy life expectancy are present globally irrespective of a country's quintile on the socio-demographic index or between sexes [ ] . this implies that quantity is more prevalent than quality of life worldwide. the disabling outcomes of a disease such as t dm has considerable implications for the health care system plans and disbursements [ ] . economic status and healthcare t dm presents with economic, social and health burdens not only for the individual but also for families and careers as well as the healthcare system. additionally, employment is another social factor which is often impacted, leading to further strain on the country's economy [ ] . a country's ability to prevent t dm lies in the presence of an identification and targeting strategy aimed at high risk individuals. this is dependent on the infrastructure and human resources available with a consequential effect on the management plan of the diagnosed individuals [ ] . furthermore, statistical data regarding epidemiology would be essential for health care providers in the identification of the risk factors contributing to t dm at a country level. this would aid in surveilling, diagnosing, monitoring as well as treating t dm. in previous studies diabetes was reported to be more common with individuals with high socio-economic status [ ] [ ] [ ] . in contrast, a recent study reported that a higher t dm prevalence was associated with individuals having a lower socioeconomic status due to limited access to health care and [ ] . moreover, this factor was also observed in low and middle income asian countries experiencing fast economic advancement [ ] . coronaviruses are enveloped viruses known to cause respiratory infections in humans. whilst most of these viruses are harmless and cause mild symptoms, a novel virus known as sars (severe acute respiratory syndrome) -cov as well as covid- emerged in december of , which proved to be more harmful than the previously known coronaviruses [ ] . it is now a known fact that co-morbidities such as obesity, diabetes mellitus (dm), hypertension as well as advanced age all increase the chances of being infected with covid- [ ] . additionally, reports from the centres for disease control and prevention stated that patients with diabetes and metabolic syndrome might be times more likely to die due to covid- [ ] . there are several possible mechanisms which can make diabetic patients more susceptible to covid- . some of these mechanisms include; impaired macrophage activity; impaired neutrophil recruitment and cytokine storm. however, the one mechanism which seems to be considered most is the increased viral load due to the virus entering the cells efficiently. in fact, the receptor which this virus uses is the angiotensin-converting enzyme (ace ) receptor which can be found expressed by various tissues including lungs, kidneys, pancreas and the heart [ , ] . firstly, the sars cov- spike protein bind to the ace cell surface where the s protein is then primed by the cellular proteases such as tmprss and furin. priming involves cleaving the s protein at the s /s domains, allowing the virus to fuse to the cell surface [ ] . virions are then taken up into endosomes where the sars cov is cleaved and possibly activated by cathepsin l [ ] . inside the cell sars cov replicates itself whilst ace catalyzes the conversion of angiotensin i to angiotensin ii and ace converts angiotensin ii to ang - [ ] . since ace receptors are also found in the pancreas, the entry of coronavirus in the pancreatic cells may result in acute beta cell dysfunction [ ] . finally this may lead to a state of acute hyperglycaemia which if left uncontrolled predisposes the diabetic individual to a greater risk of infection and also a higher chance of mortality [ , ] . certain medications prescribed to diabetic patients such as glp- agonists, angiotensin receptor blockers (arb's) and angiotensin converting enzyme inhibitors (acei's) are thought to upregulate ace expression [ ] . acei initially inhibits the angiotensin converting enzyme (ace) leading to decreased angiotensin i levels. this possibly causes a negative feedback loop that ultimately upregulates more ace receptor which can now interact with the decreased angiotensin i substrate available [ , ] . additionally, evidence of a -fold increase in ace levels with lisinopril and a -fold increase in ace levels with losartan was also published [ , ] . therefore, due to the ace receptor being expressed in various tissues as well as due to the upregulation of ace receptor there is thus an increase in potential binding sites for sars-cov- . this mechanism takes place in patients with diabetes and/or hypertension since they usually take acei or arb's. hence, infection by covid- may be more severe in these patients [ , ] . whilst the above mentioned mechanism seems to confirm that arb's and acei's upregulate ace expression, other studies which contradict this have been published. these studies claim that the administration of these medicines is actually beneficial to patients infected with covid [ ] [ ] [ ] [ ] . lack of exercise one of the many mitigation legislations put forward by governments along with public health authorities to contain the spread of covid- was to institute social-distancing restrictions along with the closure of gyms and parks [ ] . furthermore, the population was advised to limit going out of their homes unnecessarily [ , ] . exercise has long been established to be an important requisite as part of the diabetes management and prevention plans [ ] . several studies carried out over the years found that lifestyle interventions including min/week of physical activity and diet-induced weight loss of - % reduced the risk of progression from impaired glucose tolerance (igt) to type diabetes by % [ ] [ ] [ ] . a systematic review and meta-analysis carried out on structured exercise interventions also concluded that structured exercise programs had a statistically and clinically significant beneficial effect on glycaemic control [ , ] . consequently, the world health organization (who) released a guideline called 'stay physically active during quarantine' which contains possible ways to stay active during covid- . the use of online classes and videos were encouraged as were frequent walking breaks around the house [ ] . the mandated lockdowns resulted in the limited access to fresh fruit and vegetables. individuals including those with diabetes might have resorted to the consumption of long shelf-life canned or packaged foods that are typically high in calories and/or fats, with a potential increase in the consumption of carbohydrates [ ] [ ] [ ] . such food consumption increases the risk of weight gain and impose a higher cardiovascular, thrombotic and respiratory complications [ , ] . the concurrent presence of obesity within the diabetes population poses additional detrimental effects on the functioning capabilities of the lungs lead to a decrease forced expiratory volume (fev) and forced vital capacity (fvc) [ ] . additionally, it has been hypothesized that pulmonary lipofibroblasts together with normal adipocytes play a role in the pathogenic response of covid- . this is believed to be brought about by the increased expression of the ace- receptors which turns the adipocytes into reservoirs for the virus. moreover, the adipocytes aid in the transdifferentiation of lipofibroblasts into myofibroblasts leading to pulmonary fibrosis. consequently, the presence of fibrosis leads to severe outcomes of the covid- infection among the diabetesobese population [ ] . a recurrent issue during lockdown appeared to be an increased 'mental stress' and changes in sleeping habits [ ] . anxiety mainly stemmed from contracting the virus, being restricted to the place of residence for a long period of time and also not being able to meet with loved ones [ ] . the increased levels of anxiety were reported by more than % of the participants from north india who stated that they were worried about covid- , out of which . % reported difficulties in sleeping [ ] . another study carried out in china reported that . % of participants sustained a moderate to severe impact on their mental health due to covid- pandemic [ ] . fig. in the supplement material is a guideline released by the national diabetes service scheme (australia) intended in helping with management of worries and anxiety related to covid- and diabetes [ ] . similarly, the european country of malta also released a set of recommendations to help the local diabetic population in managing their condition as well as to reduce anxiety related to covid- [ ] the national health service (nhs) also published 'guidance for: supporting people with diabetes during the covid- pandemic' which compiles informative websites that the diabetic population might need to access during these difficult times [ ] .apart from these guidelines, a number of countries including the european country of malta, set up designated helpline to provide aid to all those experiencing mental health issues including the diabetes population [ , [ ] [ ] [ ] . whilst covid- and the subsequent stress can be a source of sleep disturbance, one has to also take into account diet; lifestyle and diseases [ ] . in fact, shorter sleep duration and unstable sleeping patterns have been linked to obesity and cardiovascular problems [ , ] . an association was also found between sleep disorders and patients with t dm, where increased rates of insomnia, excessive sleeping during the day and a more frequent use of sleep medications were reported [ ] . these changes in sleeping patterns may be due to the t dm itself as well as due to complications which come with it such as polyuria and peripheral nephropathy [ ] . lockdown restrictions challenged individuals including those with diabetes with inadequate vitamin d levels due to low sunlight exposure during this pandemic [ ] . vitamin d deficiency can lead to an increased mortality and morbidity due to covid- [ ] vitamin d supplementation is not only thought to decrease the risk of infection but it is also being suggested as a cure for infection patients [ ] vitamin d has numerous mechanisms through which it decreases the risks of microbial infections and death. these mechanisms can be grouped into three main categories; physical barrier, cellular natural immunity and adaptive immunity [ ] . it was observed that infected elderly with diabetes had an elevated fasting blood glucose as opposed to their hba c which remained stable [ ] . however, during the acute phase of the covid- infection it is essential that strict glucose control is maintained to prevent the occurrence of complications [ , ] . a number of healthcare recommendations and guidelines have been issued during these unprecedent times by different stakeholders including the institute for healthcare excellence on managing the diabetic population pre-covid- [ ] . examples of these recommendations can be found as part of the supplement material (supplement tables , change in healthcare services due to covid- individuals with diabetes are not always able to self-cafe and modify drug doses, especially those in marginalised and disadvantaged populations as well as elderly deprived of social support. these populations are dependent on health professionals [ ] . in such cases, where no designated point of reference is available, managing their own condition can place further psychological stress on the patients, which might have been the case during the covid- lockdown periods. complications arising from poorly managed blood glucose such as diabetic ketoacidosis raises the risk for morbidity and mortality. this will not only put a strain on an individual and the family unit but also on the health care system [ ] . most outpatient services were temporary halted during the pandemic whilst those that continued their services were challenged due to staff reduction as these were deployment to frontline duties or illnesses [ ] . hence, ensuring that delivery of care does not cease during this pandemic was a great feat. virtual care was a tool employed by many countries in an attempt to continue provision of service whilst also preventing nosocomial exposure to covid- . telehealth was consequently beneficial for countries, such as usa,uk and india, when providing a service in distant locations with shortage of staff [ ] [ ] [ ] . using such technologies enabled imparted education to individuals with diabetes about changes in insulin dosing as well as general self-care. the ongoing communication empower individuals and allow them to independently manage their condition. studies carried out prior to the pandemic indicated that virtual communication can successfully lower hb a c [ ] . practitioners through telemedicine can further emphasize the importance of controlling glucose levels as well as relate the potentially improved outcomes of covid- if encountered [ ] . however, such a tool is not always viable due to limited accessibility, acceptance and knowledge on the use of technology. in fact, some individuals still requested to be seen in the traditional face-to-face setting [ ] . moreover, practitioners in developing countries should always consider financial implications of therapies on an individual. simple treatment regimens and low-cost therapy should ideally be prescribed especially to underprivileged populations [ ] . the guidelines observed in supplement fig. have formulated by the british national health system (nhs) to assess the risk of covid- susceptibility before setting up an outpatient assessment or follow up [ ] . healthcare professionals can potentially encounter clients who are awaiting result or have been confirmed as covid- positive. hence it is essential to encourage staff to wear ppes whilst also adhering to recommended sanitisation procedures; especially in aerosol generating practices. such procedures should also be enforced in hospital routine activities such as waste, food, utensil and laundry handling. bornstein et al., compiled a list of guidelines for healthcare workers to follow when dealing with diabetic patients in different scenarios. these guidelines can be found in fig. in the supplementary material [ ] . easy and practical recommendations that were compiled by wang et al., ( ) that can be relayed to patients are listed in fig. which can be accessed in the supplement material [ ] . the extensive impacts on health revealed by this pandemic has demonstrated the vulnerability of individuals with noncommunicable diseases (ncds) [ ] . a study carried out in italy showed that % of patients that died in hospitals had previous comorbidities, with t dm being second highest amongst hypertension, malignant tumours, cardiac and respiratory diseases [ ] . the link between ncd and covid- mortality has also been made in usa, china and spain [ , , ] . measures undertaken for ncds included quarantine and physical distancing. this could potentially result in poor management of the condition by both the patient -through behavioural risk factors -and the healthcare professional [ ] . rescheduling of routine medical tests and appointments can further hinder management as well as limited access to primary healthcare centres, pharmacies and transport. all these factors will make it tougher to ensure continuity of care. research from other pandemics indicates that exacerbation of ncds occurs without proper healthcare management [ ] . this is due to stress that is brought about by changes in routine, uncertain economic situations and new regulations which will ultimately raise rates of disability, morbidity and mortality in patients with ncds [ ] . the importance of t dm management to avoid serious repercussions on health and overall economy is not a new concept. hence it is important to equip patients with the right knowledge about the current pandemic and its possible effects on their overall health. it is crucial, now more than ever, to ensure that patients have direct contact with a healthcare practitioner to mitigate any queries or concerns that they may have. this will ultimately empower individuals to adhere to recommendations whilst also avoiding extra stressors which may exacerbate hyperglycaemic effects such as kidney failure, amputation, nerve damage and heart disease [ ] . t dm has been a global burden for decades; however, additional burden has been imposed with the onset of covid- pandemic. consequently, at a global level, healthcare systems as well as the diabetes population were impacted during this pandemic. mitigation restrictions that were aimed to curb the spread may have imposed a higher burden on the diabetes population. having an understanding of the different challenges and subsequent burden faced by this vulnerable population will enable healthcare professional, healthcare provision and policy makers to provide targeted action plans. funding no funding was received to conduct this study. 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non-communicable diseases in emergencies difficulties to treatment adherence according to the perception of people living with type diabetes publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -pjscmen authors: caballero, a.e.; ceriello, a.; misra, a.; aschner, p.; mcdonnell, m.e.; hassanein, m.; ji, l.; mbanya, j.c.; fonseca, v.a. title: covid- in people living with diabetes: an international consensus date: - - journal: j diabetes complications doi: . /j.jdiacomp. . sha: doc_id: cord_uid: pjscmen the covid- pandemic has added an enormous toll to the existing challenge of diabetes care world-wide. a large proportion of patients with covid- requiring hospitalization and/or succumbing to the disease have had diabetes and other chronic conditions as underlying risk factors. in particular, individuals belonging to racial/ethnic minorities in the u.s. and other countries have been significantly and disproportionately impacted. multiple and complex socioeconomic factors have long played a role in increasing the risk for diabetes and now for covid- . since the pandemic began, the global healthcare community has accumulated invaluable clinical experience on providing diabetes care in the setting of covid- . in addition, understanding of the pathophysiological mechanisms that link these two diseases is being developed. the current clinical management of diabetes is a work in progress, requiring a shift in patient-provider interaction beyond the walls of clinics and hospitals: the use of tele-medicine when feasible, innovative patient education programs, strategies to ensure medication and glucose testing availability and affordability, as well as numerous ideas on how to improve meal plans and physical activity. notably, this worldwide experience offers us the possibility to not only prepare better for future disasters but also transform diabetes care beyond the covid- era. chinese geriatric endocrine society issued guidance to plwd on coping with the situation. , expert recommendations on insulin treatment of hyperglycemia in patients affected with covid- was also developed to guide hyperglycemia management in hospitalized patients. many endocrinologists offered free consultation to plwd through internet-based consultation platforms. based on the experience with sars, it is predicted that this pandemic will be of short duration, so, advice has focused on how to discover and prevent hyperglycemic crisis. according to chinese guidelines, a slight elevation of glucose above the recommended target is tolerable for a short period of time. but patients should be aware of early signs of significant hyperglycemia crisis and when to go to the hospital. a very detailed guidance for plwd was created on how to access certified internet-based medical services and medical supplies through smartphones. a location-based gps diabetes pharmacy map was also developed, providing information on pharmacies with insulin to ensure that plwd are able to access their medicines through non-hospital channels. the map has been viewed by more than . million people and its related information has reached million. for those plwd urgently needing to see health care providers in hospital, information was j o u r n a l p r e -p r o o f based public media, such as baidu (a google equivalent) and wechat, used by more than million people living in china. the mean prevalence of diabetes in europe in people affected by covid- has been reported to be % by the who europe region. italy was the first country in europe affected by . the situation in the north of the country was dramatic while in the southern area it remained under control. the second country showing a similar trend was spain; the epidemic was very serious in the areas of madrid and barcelona and less so in other parts. italy and spain adopted the -lockdown‖ strategy quite quickly, closing almost all activities and keeping their citizens at home. this lockdown was also rapidly adopted in several other countries, possibly explaining why the disease left countries like portugal and greece virtually unaffected. conversely, where the lockdown was adopted late in the appearance of covid- , the related morbidity was higher. for example, the uk experienced a high total number of cases, and sweden a high number of cases as a proportion of their small population. russia has a different story: at the beginning the situation was unclear but today this country displays the worst situation in europe. the world health organization issues daily situation reports to communicate all updates by country and region. j o u r n a l p r e -p r o o f but upon lifting the lockdown there has been a major surge. mortality due to covid- in india has remained lower than many other countries: ~ %. india has a huge number of patients with diabetes; specifically, million patients above years of age who are particularly vulnerable to mortality due to covid- . these large numbers of patients pose a major challenge in prevention and management. further, during the lockdown, patients with diabetes have increased snacking/carbohydrate intake and decreased physical activity, resulting in weight gain, which may de-stabilize glucose control. a simulation model analysis showed a significant association between the duration of the lockdown and loss of glycemic control as well as associated complications. the predicted increment in hba c from baseline at the end of days and days lockdown was . % and . % respectively. similarly, the predicted percentage increase in complication rates at the end of day lockdown was . % for retinopathy, . % for microalbuminuria, . % for proteinuria, . % for peripheral neuropathy, . % for lower extremity amputation, . % for myocardial infarction, and . % for stroke. these data show a likely increase of patients with diabetesrelated complications, adding to already huge numbers. in addition, according to another recent analysis, a % increase in diabetes risk will occur consequent to weight gain during lockdown. if this occurs, millions of new cases of diabetes will be diagnosed in the near future. j o u r n a l p r e -p r o o f inability to access the online link, poor quality of picture, poor perception of sound, etc. indeed, many patients prefer telephone or smartphone-based tele-consults. one of the widely debated questions regarding the covid- epidemic is why overall mortality due to covid- in india lower than other countries. adverse factors which could lead to increase in mortality are all too pervasive in asian indians: poorly controlled diabetes and hypertension, high prevalence of cardiovascular diseases, increased baseline sub-clinical inflammation, and increasing obesity. there could be other factors which could be protective but need research. firstly, bcg vaccination may have a role in enhancing innate immunity. countries which have a universal bcg vaccination (including india) have a lower mortality due to covid- as compared to other nations. second, cytokine storm, associated with high mortality in covid- cases, may be muted in indians due to previous recurrent infections (malaria, previous coronavirus, etc). these and several other issues have been discussed in a recent review. what will be the scenario for covid- related mortality and hospitalization in the next months? it is difficult to predict but some indicators are available from the model of harpreet in summary, while overall mortality due to covid- is lower in india than in other countries, the elderly population, where most patients with diabetes, hypertension and cvd are concentrated, remains at high risk. several solutions are suggested in table . , perspective from the middle east the middle east (me) has a huge range of variability in wealth, strength of the health system as well as in density of the population, where some countries are < million in population while others are > million. consequently, these variations are also reflected in the response to covid- with regards to the ability to implement robust social distancing, effective and timely use of protective measures, and in the ability to test suspected cases. many studies on covid- are ongoing and the results of these studies are not yet published. however, recent data from kuwait are now available, although not yet peer-reviewed. in a single hospital where % of covid- patients were admitted, the total number of admissions was persons and case fatalities were . %, with mean age . ± . . male gender represented % of all fatalities and diabetes was diagnosed in % of those who died. this observation matches the recent announcement by the united arab emirates government spokesperson, where % of covid-j o u r n a l p r e -p r o o f years in kuwait ( . %) and in those aged - years ( . %) . future data from other middle east countries are eagerly awaited. one aspect was common across the me: ramadan fasting, as ramadan this year started on rd of april, which coincided with the peak of covid- in many countries. while the majority of the me population are muslims, this issue extends to millions of muslims globally where fasting during the month of ramadan is something they await passionately each year. the vast majority of plwd fast safely during ramadan. however, for some there is increased risk of hypoglycemia, hyperglycemia, ketoacidosis, dehydration, and thrombosis. furthermore, many plwd are treated with sglt inhibitors (sglt -i) in view of the recent cardiovascular outcomes trials. however, some were concerned about the possibility of dehydration during ramadan fasting for people treated with this class of medication, as well as the concern regarding diabetic ketoacidosis in those patients with covid- on sglt -i. in response to the question of the safety of ramadan fasting for plwd, the diabetes and ramadan international alliance has provided guidance that is available on the idf website. as the coronavirus epidemic spread throughout the me, many clinicians and plwd looked for approximately % of all cases of covid- in the world have been reported in the u.s. race/ethnicity has been recorded in only % of them. among these cases, racial/ethnic minorities stand out as being disproportionately affected by covid- . for example, . % of covid- cases are in blacks, . % in latinos/hispanics and . % in non-hispanic whites while they represent . %, . % and . % of the general u.s. population respectively. , most cases have been reported in people ages to years, followed by those ages to years. however, most hospitalizations indicating severe disease have been in individuals above years. the prevalence of diabetes is on the rise in the u.s. at the present time, it is estimated that at least in individuals above years of age has diagnosed diabetes. however, among those journal pre-proof j o u r n a l p r e -p r o o f between - and among those above , approximately in have diagnosed diabetes. it is not surprising then that diabetes has been frequently reported as an underlying condition in people diagnosed with covid- but even more significantly among those who have been hospitalized and in those who have died from covid- . , the covid- pandemic is a reminder of a previous major disaster to hit the u.s.: hurricane katrina, during and after which plwd were seriously affected by not having access to healthy meals, medications like insulin, etc. major disasters usually lead to worse diabetes control among most plwd. people with lower socio-economic status and access to health care are often affected in a more impactful manner. in response, the american diabetes association formed a disaster preparedness task force that made recommendations about diabetes management when faced with an emergency (table ) . clinicians should be reminded to access and use these resources, freely available online. just as we teach all our patients that they should prepare for an emergency, so should healthcare provider organizations ensure that direct patient medical care will continue in some way, and that patients are aware of means by which they can access their medication-including experimental medications. there is no doubt that people with diabetes are not only widely affected by covid- but very often have a more severe form of the disease. we have learned that in addition to the presence of co-morbidities, the level of hyperglycemia during the disease can seriously affect the outcomes. , the survival rate in hospitalized patients with type diabetes with well-controlled j o u r n a l p r e -p r o o f blood glucose is almost % (considering a threshold of glycemia < mmol/l or < mg/dl), while above this threshold the survival rate is only %. in the same study, hyperglycemia was associated with worse prognosis of covid- in both people with and without diabetes. hyperglycemia, particularly severe hyperglycemia, is often a marker of the severity of the underlying comorbidities. thus, hyperglycemia can serve as a marker of high risk of morbidity and mortality in the covid- infected patient, as was similarly observed for the sars epidemic in . there is some evidence suggesting how hyperglycemia is generated or worsened during covid- , depicted in figure . sars-cov- may affect β-cells, causing a reduction of insulin secretion. sars-cov- infection is also accompanied by a significant production of cytokines, which can induce insulin resistance. both reduced insulin secretion and insulin resistance may result in hyperglycemia, which in turn may further decrease insulin secretion and increase insulin resistance. hyperglycemia also generates non-enzymatic glycosylation. glycosylation of the ace receptor can facilitate the entry of the sars-cov- into host cells. furthermore, acute hyperglycemia, either directly or through cytokine production, may provoke endothelial dysfunction and thrombus formation, which in turn can lead to organ damage and fatal outcome of the disease. this hypothesis is consistent with the evidence of high levels of d-dimer in people with diabetes, particularly people with poor glycemic control, during the course of covid- . j o u r n a l p r e -p r o o f several important pathways have been linked between covid- and diabetes that could be considered as targets for therapy related to diabetes and comorbidities. the first is dpp- , a known receptor for coronaviruses including mers and sars but not sars-cov- . however, even though dpp- is involved in the inflammatory cascade, its role is minimal. there is currently no evidence that dpp- inhibitors (dpp- i) have any beneficial effect on covid- infected patients. a second, interesting pathway is the enzyme angiotensin converting enzyme- (ace ), which does function as a receptor of coronavirus, including sars-cov- . it is known that ace is involved in conversion of angiotensin i to angiotensin ii and ace inhibitors are commonly used in the management of hypertension. it's also known that ace acts on ang ii to produce a fragment that is beneficial, as it is involved in increasing blood flow, is cardio-protective and decreases insulin resistance. ace is also present in the pancreas, where its role in diabetes is unclear. a rational hypothesis is that in binding to ace the virus may affect organs where it is present and thereby the sars-cov- virus may be affecting the pancreas and causing hyperglycemia. obesity is an additional contributing factor to the deleterious outcomes in plwd and covid- as its state of low-grade, chronic inflammation seems to be amplified following sars-cov- infection. we still need to better understand this effect before we can effectively target this exacerbated inflammatory state and its frequent coagulation response that seems to be the trigger for severe disease and mortality. finally, the increase in blood glucose levels associated with covid- described above could potentially occur not only in people with known diabetes but also in those with undiagnosed diabetes, prediabetes or with major predisposition to the disease. the potential deleterious effects of sars-cov- on ß-cells and on insulin resistance may partially explain the covid- -related new-onset diabetes cases identified in several countries/regions. understanding the precise mechanisms leading to this phenomenon will be extremely important in order to generate corresponding clinical management guidelines. as previously stated, plwd are more prone to a serious form of covid- . optimizing glycemic control is key to reducing the risk of serious disease as well as successfully treating people who have been hospitalized with covid- . the comprehensive management of associated comorbidities and the evaluation of biomarkers for cardiovascular risk are equally important during this critical time. , the principles of managing diabetes in association with any acute illness apply in those affected with covid- , with a few caveats. the biggest challenge is for health care systems to manage seriously ill patients in isolation, with limited staff and the well-known challenges regarding the availability of personal protective equipment. these conditions limit the ability to implement glucose monitoring and intravenous administration of insulin and fluids. despite these challenges, it seems prudent to target blood glucose levels below mmol/l or mg/dl as in most hospitalized patients with diabetes. clinical studies to demonstrate this strategy is in fact conducive to better patient outcomes in the setting of covid- are needed. insulin therapy is the preferred strategy to improve glycemic control in hospitalized patients, and reducing the risk for ketoacidosis and hypoglycemia is a core goal. insulin schemes either using subcutaneous basal-bolus therapy or intravenous continuous infusion can be used. insulin doses may be higher than usual due to augmented insulin resistance in these patients. in light of a possible mortality benefit from the glucocorticoid dexamethasone in those with respiratory failure due to covid- , the adoption of specific insulin strategies to address steroid-induced hyperglycemia is also needed. oral anti-diabetes medications can be used in mild covid- cases without severe hyperglycemia as long as they are not contraindicated. as previously stated, there is insufficient evidence to specifically recommend dpp- i for the treatment of diabetes in the setting of covid- . while metformin and sglt- i may have a beneficial effect in heart failure, and epidemiologic studies suggest a possible survival advantage among those treated with metformin , these medications need to be tested in randomized clinical trials in the setting of covid- before making any formal recommendations. furthermore, clinicians should be very cautious about the risk of lactic acidosis or ketoacidosis in patients who are severely ill and not eating or hydrating themselves well while on these medications. dehydration could also impose j o u r n a l p r e -p r o o f could interfere with ace to decrease its breakdown, which in turn would facilitate the penetration of sars-cov into host cells. however, the clinical implication is highly questionable to the point that several international organizations have made a very clear statement that providers should encourage patients to continue to use these medications if needed. , tracking blood glucose levels in hospitalized patients is key to achieving effective diabetes control. until the epidemic hit, hospital continuous glucose monitoring (cgm) had not been approved by the u.s. food and drug administration (fda). insufficient data as well as concerns about subcutaneous blood flow and the lag between true blood glucose and subcutaneous interstitial fluid glucose precluded its approval. however, further data supporting a reasonable correlation between cgm and a point-of-care blood glucose testing in non-icu patients, and between flash glucose monitoring and capillary blood glucose testing in hospitalized patients, along with the urgent need to better manage patients with diabetes and covid- , prompted the fda to grant approval for the use of cgm systems in the hospital. adoption of cgm for inpatient use requires careful consideration and expertise, and more guidance would be beneficial for hospital-based clinicians. the covid- and diabetes pandemics have imposed an unprecedented challenge on the lives of millions of people around the world. improving diabetes control in the outpatient setting at we have the obligation as health care professionals to raise awareness and address to the best of our abilities all social determinants of health that clearly increase the risk of diabetes, covid- and many other health threats. we also have the opportunity to improve the lives of plwd beyond the covid- era by addressing patients as a whole, beyond the usual biomedical model. the management of chronic diseases like diabetes has long been an enormous challenge. the current model of health care based on patients receiving services at clinics and hospitals has been effective for many but not all plwd. the -forced‖ used of telemedicine or virtual care during this pandemic has been beneficial to many plwd and other chronic conditions. although it is clear that this option of care is not available to most people around the world, exploring how to improve the communication between providers and patients and families at home, in their own communities facing day to day challenges, may prove to be a more effective approach to managing the disease well beyond the covid pandemic. indeed, rather than going back to the pre-covid- diabetes care model, we should take advantage of what we are learning and innovating during this time to improve diabetes care strategies in the post-covid- era. in addition, this experience will help us be better prepared for future disasters (figure ). j o u r n a l p r e -p r o o f finally, we recognize that as we all continue to learn about covid- and its consequences, sharing our collective experience is critical to the ultimate goal of developing evidence-based recommendations to better guide the management of diabetes during this challenging time and beyond. j o u r n a l p r e -p r o o f clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study clinical characteristics of coronavirus disease in china clinical characteristics and outcomes of patients with severe covid- with diabetes prognostic factors in patients with diabetes hospitalized for covid- : findings from the coronado study and other recent reports covid- and endocrine diseases. a statement from the diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations predicting mortality due to sars-cov- : a mechanistic score relating obesity and diabetes to covid- outcomes in diabetes and covid- : more than the sum of two morbidities diabetic patients with covid- infection are at higher risk of icu admission and poor short-term outcome covid- : black people and other minorities are hardest hit in us is ethnicity linked to incidence or outcomes of covid- ? disparities in the population at risk of severe illness from covid- by race/ethnicity and income chinese center for disease control and prevention. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china expert recommendations for diabetes management in primary care during the covid- pandemic guidance on diabetes management in the elderly during the covid- pandemic recommendations on insulin treatment in diabetes patients affected with covid- covid- weekly surveillance report: data for the week of - world health organization. coronavirus disease (covid- ) situation reports clinical considerations for patients with diabetes in times of covid- epidemic estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: a simulation model using multivariate regression analysis increase in the risk for type diabetes due to lockdown for covid pandemic in india: a cohort analysis telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians roadblock in application of telemedicine for diabetes management in india during covid pandemic the links between covid- and diabetes, known and unknown diabetes during the covid- pandemic: a global call to reconnect with patients and emphasize lifestyle changes and optimise glycemic and blood pressure control covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india clinical characteristics of coronavirus disease (covid- ) patients in kuwait the prevalence of pre-diabetes and diabetes in the kuwaiti adult population in diabetes and ramadan: practical guidelines international diabetes federation e-library. diabetes and ramadan: practical guidelines available at: www.diabetesatlas.org/en the hurricane katrina aftermath and its impact on diabetes care: observations from "ground zero": lessons in disaster preparedness of people with diabetes impact of a natural disaster on diabetes: exacerbation of disparities and long-term consequences american diabetes association statement on emergency and disaster preparedness: a report of the disaster response task force association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes outcomes in patients with hyperglycemia affected by covid- : can we do more on glycemic control? diabetes care plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with sars why is hyperglycemia worsening covid- and its prognosis? diabetes obes metab coronavirus infections and type diabetes-shared pathways with therapeutic implications new-onset diabetes in covid- hyperglycemia and the worse prognosis of covid- . why a fast blood glucose control should be mandatory diabetes and cardiovascular disease (d&cvd) issues of cardiovascular risk management in people with diabetes in the covid- era covid- and diabetes management: what should be considered? practical recommendations for the management of diabetes in patients with covid- pragmatic approach to inpatient diabetes management during the covid- pandemic metformin treatment was associated with with decreased mortality in covid- patients with diabetes in a retrospective analysis are patients with hypertension and diabetes mellitus at increased risk for covid- infection? european society of cardiology. position statement of the esc council on hypertension on ace-inhibitors and angiotensin receptor blockers heart failure society of america, and american college of cardiology. patients taking ace-i and arbs who contract covid- should continue treatment, unless otherwise advised by their physician continuous glucose monitoring in insulin-treated patients in non-icu settings implementation of continuous glucose monitoring this work was based on a livestreamed educational conference organized by the postgraduate medical education department at harvard medical school and supported by an educational grant from sanofi. the sponsor had no involvement in the conference content or in the development of this manuscript. we appreciate the assistance provided by karen j. kuc, mph in the compilation and editing of the manuscript. key: cord- -yw qgv authors: lisco, giuseppe; de tullio, anna; giagulli, vito angelo; guastamacchia, edoardo; de pergola, giovanni; triggiani, vincenzo title: hypothesized mechanisms explaining poor prognosis in type diabetes patients with covid- : a review date: - - journal: endocrine doi: . /s - - - sha: doc_id: cord_uid: yw qgv purpose: epidemiological data suggest that comorbid patients, mostly those with type diabetes (t d), are predisposed to poor prognosis in coronavirus disease (covid- ), leading to serious healthcare concerns. the aim of the present manuscript is to review the main relevant mechanisms possibly contributing to worsen the clinical course of covid- in t d. results: poor glucose control, high glycaemic variability and diabetes-related comorbidities at baseline, particularly cardiovascular diseases and obesity, contribute in worsening the prognosis in the above-mentioned cluster of patients. moreover, both a lower efficient innate immune system response and cytokine dysregulation predispose patients with t d to impaired viral clearance and more serious pulmonary and systemic inflammation once the sars-cov- infection occurred. inconclusive data are currently available for specifically indicate or contraindicate concurrent medications for managing t d and its comorbidities in infected patients. conclusions: t d individuals should be considered as more vulnerable to covid- than general population, and thus require adequate advices about hygienic tips to protect themselves during the pandemic. a careful management of glucose levels and diabetes-related comorbidities remains essential for avoiding further complications, and patient monitoring during the pandemic should be performed also at distance by means of telemedicine. further studies are needed to clarify whether medications normally used for managing t d and its associated comorbidities could have a protective or detrimental effect on covid- clinical course. background firstly identified and characterized as -ncov [ ] , human severe acute respiratory syndrome coronavirus (sars-cov- ) has been reported as a novel infective agent arisen at the end of the [ ] . sars-cov- is a positivesense, single strand, enveloped rna virus belonging to the family of coronaviridae, and is the th beta-coronavirus recognized to infect humans [ ] . first metagenomic rna sequencing of sars-cov- showed the single-strand rna consisted of , nucleotides, and was closely related to a group of bat sars-like coronaviruses ( , %) [ ] . further observations confirmed that sars-cov- was closely related ( %) with two bat sars-like coronavirus (bat-sl-covzc and bat-sl-covzxc ), but was distant from other two human coronaviruses responsible for severe infective pneumonia: sars-cov ( %) and middle east respiratory syndrome coronavirus (mers-cov) ( %) [ ] . a high grade of homology between genomic sequences of sars-cov- form different patients ( . %) has also been reported, thus confirming a human-to-human transmission of the novel infective agent [ ] . phylogenetic analysis suggested that sars-cov- progenitors circulated in animal host including bats [ ] , snakes, malayan pangolins, civets, mouse [ , ] , and underwent to a naturally occurred selection before the zoonotic spillover finally adapting to persistently infect the new host [ ] . official epidemiological report declared that the early cases of infections were detected in december , and involved people who worked or visited the hua nan south china seafood market [ ] , in wuhan capital city (hubei province; people's republic of china). however, it remains still debated whether the zoonotic spillover might have been occurred in other places [ ] , particularly in southeast asia [ ] , and consequently sars-cov- infection might have been imported to wuhan. epidemiological analysis showed a marked widespread of the infection within community places due to a large human-to-human transmission [ ] and wuhan rapidly became the hub of a new pneumonia outbreak [ ] . due to a consistent widespread of detected cases among several countries, the world health organization declared the state of pandemic on march , when confirmed cases raised up to , , and sars-cov- spread into countries [ ] . clinical manifestations of the novel coronavirus disease (covid- ) include fever ( %), cough ( %), dyspnoea ( %), muscle soreness ( %), chest distress ( %) in a context of bilateral pneumonia ( %) with ground glass opacification ( %) at ct scan due to lung interstitial involvement [ ] . autoptic studies described macroscopic features of pleuro-pericarditis, lung consolidation, oedema with overall increased pulmonary weight; while microscopic hallmarks are characterized by pneumocyte hyperplasia, lymphocytic and multinucleated giant cells infiltration, hyaline membranes [ ] [ ] [ ] . other signs and symptoms of covid- include acute conjunctivitis [ , ] ; diarrhoea, abdominal pain/discomfort and vomiting [ ] [ ] [ ] ; convulsion, headache, muscle soreness [ ] ; diffuse erythematous rush and widespread urticaria [ ] ; acute kidney injury [ , ] ; pharyngodynia, nasal congestion with rhinorrhoea and smell/taste impairment [ ] . sars-cov- may directly affect myocardial tissue, and significantly complicate the prognosis of underlying cardiovascular diseases [ , ] . sars-cov- infection usually occurs asymptomatically or mildly symptomatic form of the disease but in predis posed patients with specific clinical conditions, a serious clinical course could be observed thus leading to worse prognosis or death [ ] . worldwide reported case-fatality rate for covid- differs considerably among geographical areas [ ] , and could be attributable to several variables, such as testing strategies for screen suspected cases and identification of infectious patients (statistical); accessibility to intensive care according to restricted national healthcare system capacities (organization); baseline patient age and comorbidities (medical) [ , ] . from the latter point of view, a poor prognosis is usually observed in elderly patients [ ] and worldwide age-specific case-fatality rate occurred very high among patients with one or more underlying chronic diseases including cardiocirculatory, renal, pulmonary, central nervous system and mental illness, diabetes mellitus (dm) and malignancies [ , ] . according to the data shared by the italian national institute of health, patients who died while tested positive for sars-cov- exhibited an elevated mean age ( . years old), mostly men ( %) and with one or more pre-existent chronic diseases ( . in mean) [ ] . of these, blood arterial hypertension ( %) and dm ( %) were the most commonly reported clinical comorbidities, followed by ischaemic heart disease ( %) and atrial fibrillation ( %). the leading cause of deaths was attributable to acute respiratory distress ( %) [ ] . the global estimated prevalence of t d accounts for more than millions affected patients corresponding to . % of the worldwide population [ ] . therefore, the number of patients with t d who will contract sars-cov- infection is expected to be considerable, and should increase over time. t d per se does not increase the risk of contracting sars-cov- infection but could exacerbate the clinical course of covid- leading to a detrimental prognosis [ ] . indeed, the frequency of diabetes in patients with covid- has been reported to - % [ ] [ ] [ ] , raising up to - % in hospitalized patients including those who required intensive care for severe disease [ , ] . more recently, data collected from nine hospitals from seattlearea in the united states demonstrated that % of patients who required hospitalization for respiratory symptoms attributable to covid- had t d [ ] . in severely ill patients with covid- a pre-existent t d was observed in about % of the cases and, according to the results of an univariate analysis, the presence of t d resulted a significant risk factor for poor prognosis in this clinical setting (or . ; p < . ) [ ] . dm has also been reported as the main clinical condition observed in non-survived patients with covid- ( %) [ ] , thus resulting one of the most frequently associated comorbidity in covid- deceased patients [ ] . this concern has been further confirmed by the results of a cohort study among fatal cases of covid- in wuhan, hence defining dm as a potentially harmful comorbidity predisposing to worse clinical course or death once sars-cov- infection occurred [ ] . different hypothesis should be considered for explaining this clinical phenomenon, including glucose control at baseline and during the infection course, pathophysiology and immune system response in sars-cov- infected patients with t d, diabetes-related comorbidities and concomitant medications. herein, a point-to-point discussion about these putative mechanisms has been carried out. epidemiological data showed that t d represents a risk factor for infectious diseases, mostly with bacterial aetiology, particularly at the level of skin and soft tissue, genitourinary, gastrointestinal and respiratory systems [ ] . moreover, life expectancy in individuals with t d may be affected due to infectious diseases and in certain clusters of patients, such as in elderly with t d, the leading cause of mortality is attributable to severe pulmonary infections rather than other highly prevalent comorbidities, including cardiovascular diseases and malignancies [ ] . on the other hand, dm increases the cumulative risk of medical consultation, hospital admission, intensive care requirement and poor prognosis because of pandemic influenza [ ] . further data reported that airways and pulmonary infections with different aetiologies, including sars and mers, were more frequently diagnosed in t d patients, also showing a severe clinical course [ ] [ ] [ ] [ ] . in dm, hyperglycaemia is considered one of the most important factor in determining this burden [ ] . indeed, osteomyelitis, soft tissues infections, endocarditis, tuberculosis and sepsis are most commonly observed in diabetic patients with poor glycaemic control compared to those who achieve better glucose management, and a worse glucose control contributes to increase the rate of hospitalization and mortality, too [ ] . both hyperglycaemia and high glucose variability may consistently complicate the clinical course also in case of influenza a [ ] . more recently, a retrospective observational study recruiting more than cases of covid- from hubei province (china) and including patients with a pre-existent t d displayed a higher mortality rate (hr . ), more prevalence of multiorgan damage and a greater requirement of medications (antibiotics, systemic corticosteroids, vasoactive substances, oxygen inhalation and either non-invasive or invasive mechanical ventilation) in patients with dm than in nondiabetics [ ] . interestingly, authors also found that, among t d patients, those with better glucose control (glucose levels between and mg/dl) respective to those with worse glucose control (> mg/dl) during hospitalization exhibited a significantly lower rate of mortality (hr . ; p < . ), and a fewer risk of progression to acute respiratory distress syndrome (hr . ; p < . ), acute kidney (hr . ; p < . ) and myocardial (hr . ; p < . ) injury [ ] . similar results were found by another observation in which worse glucose control (glucose levels > mg/dl) at the admission and during hospitalization was found to be an independent risk factor for progression to critical ill or death among t d patients with confirmed covid- [ ] . therefore, hyperglycaemia represents a relevant matter in patients with covid- fostering poor prognosis once the infection occurred. in addition, recent evidences suggest that sars-cov- may induce beta-cells damage thus leading to insulin secretion impairment. this phenomenon, in addition to a pre-existent hyperglycaemia and considering that systemic inflammation due to the infection exacerbates the insulin-resistance, is thought to play a significative role to further worsen glucose control and complicate the clinical course of covid- [ ] . in conclusion, epidemiological data suggested that dm, particularly t d, is a frequently observed comorbidity in patients with sars-cov- infection who require hospitalization, more intensive treatment and exhibit poor prognosis or death. poor baseline and ongoing glucose control in hospitalized patients rather than the presence of t d per se seems to facilitate covid- progression [ ] . hence, an optimal and timely blood glucose management during pandemic should be considered as an effective strategy to reduce the probability of hospitalization requirement of infected patients, and for improving the clinical course of those hospitalized for receiving either non-intensive or intensive care. innate and adaptive immune responses play a crucial role against viral infections [ ] . immune response against coronaviruses has been reviewed elsewhere, highlighting the role of both innate and adaptive systems to promptly contrast virus replication, facilitate virus clearance, stimulate tissue repair and develop persistent defence [ ] . immune response in covid- is not still completely understood making necessary further investigation to better control the pandemic evolution [ ] . however, seriously ill covid- patients exhibit an exaggerate response of neutrophils and alveolar macrophages, and a relevant peripheral lymphocytes dysfunction [ ] , which lead to an uncontrolled viral shedding, consequent viremia and further systemic immune-mediated damage, thus triggering a harmful vicious circle [ ] . glucose levels may significantly influence immune response as observed in patients with dm. natural killer (nk) cells activity is weakened in case of hyperglycaemia, and is inversely related with fasting plasma glucose, -h postprandial glycaemia and hba c levels [ ] . macrophage activation and phagocytosis are both decreased in patients with poor glucose control, but should be restored after an adequate optimization of metabolic control [ ] . neutrophil activation and phagocytosis are both impaired by hyperglycaemia as demonstrated in animal models and humans, thus suggesting a relevant impairment of innate immune response in patients with chronic hyperglycaemia [ ] . in an animal model, obese and hyperglycaemic mice experienced higher rate of respiratory infection due to influenza and bacterial pneumonia and that was related to a lower efficient alveolar macrophage response against infections. in addition, a defective toll-like receptor signalling has been recognized in neutrophils exposed to the gram-negative lipopolysaccharide, leading to a blunted release of chemokines and cytokine, and decreased myeloperoxidase activity [ ]. moreover, t-cells function is significantly dysregulated in t d and cd + lymphocytes preferentially differentiate in thelper and t-helper instead of t-helper with a consequent imbalance between pro-inflammatory and antiinflammatory activities [ ] . on the other hand, the levels of interferon gamma-which normally stimulates cd + t cells maturation in sense of t-helper rather than t-helper -were found to be lower in t d patients sera, and can contribute in a blunted t-cell response in t d [ ] . nevertheless, lower levels of interleukin (il)- have also been described in t d patients. considering that il- is capable to suppress the release of pro-inflammatory cytokines, lower levels of il- could be related with higher il- -to-ifn gamma and tnf-alpha-to-ifn gamma ratios hence suggesting an enhanced activation of circulating monocytes [ ] . high levels of il- have been detected in diabetic patients respective to those with euglycemia, suggesting that hyperglycaemia play a crucial role in determining this immunological effect [ , ] . in animal models, hyperglycaemia and insulin-resistance increase the level of circulating proinflammatory cytokines and oxidative stress at baseline [ ] . since this pro-inflammatory background usually results reversible after an effective treatment of hyperglycaemia, a low dose endotoxemia consistently enhances systemic inflammation in a animal model [ ] . therefore, hyperglycaemia may predispose to an exaggerate immune response even in case of a mild-to-moderate viral load. as known, a hyperinflammatory syndrome with cytokine dysregulation has been well recognized in seriously ill patients [ ] , thus highlighting its crucial role in serious manifestations of covid- [ ] . specific interleukins and chemokines (il- , il- , il- , tnf-alpha, interferon gamma induced protein , granulocyte-colony stimulating factor) are upregulated in patients who exhibited a worsen prognosis [ ] and particularly high levels of il- have been detected in case of serious pulmonary involvement or in patients requiring intensive care [ ] . these findings are also more evident in elderly patients who display less vigorous immune response against viral shedding, greater susceptibility to more serious pulmonary and systemic involvement, and are finally predisposed to covid- progression [ ] . both the number and function of t cells (both cd + and cd + ) [ , ] , b cells depletion, and hypercoagulability have also been observed in seriously ill cases and the greater the magnitude of these haematological and biochemical alterations then the greater the severity of the prognosis [ , ] . in conclusion, diabetic patients especially elderly individuals and those with worse baseline glucose control may exhibit immune system dysregulation that predispose them to a less effective response against sars-cov- and to a dysfunctional inflammation that requires to be carefully monitored in confirmed cases of covid- , for preventing or avoiding a harmful progression of the disease. angiotensin-converting enzyme (ace ) is a carboxypeptidase normally involved in the cleavage of angiotensin i and angiotensin ii, and is the main receptor for sars-cov- playing a determinant role in viral entry into the host, and clearly explaining both the transmissibility and severity of covid- among humans [ ] . ace is expressed at the level of several tissues (transmembrane and soluble forms), such as lung [ ] , oral mucosa [ ] , intestine [ ] , brain [ ] , pancreatic islets [ ] , testis [ ] and kidney [ ] . differentiated type pneumocytes normally express ace , which is essential to regulate pulmonary homoeostasis and protects against pulmonary injury [ ] . indeed, low levels of ace have been described in severe acute and chronic pulmonary diseases thus predisposing to poor prognosis [ ] . however, ace is overexpressed in chronic diseases, including t d, and this phenomenon could be also related with chronical exposure to several medications [ , ] . this biochemical condition is believed to facilitate the internalization of sars-cov- into pneumocytes, thus contributing to worse prognosis in covid- [ , ] . however, the role of ace overexpression in worsening the prognosis is an emergent issue, and remains currently debated [ ] . cardiovascular diseases, including coronary and cerebrovascular artery disease and heart failure, are frequently observed in t d patients and it has been estimated that about a third of them displayed these kind of complications over time [ ] . cardiovascular system is the main extrapulmonary compartment extensively involved in covid- , as suggested by a frequent myocardial involvement in affected patients especially in those having hypertension, t d and cardiovascular diseases at baseline [ ] . vascular inflammation and endothelial dysfunction [ ] , myocardial injury and cardiac arrhythmias are not-infrequently observed in covid- confirmed cases, significantly influencing the risk of poor prognosis or death in this cluster of patients [ ] [ ] [ ] . overweight-obesity syndrome is a multifactorial disease which significantly predispose to cardiometabolic risk, and is strictly associated with insulin-resistance, glucose metabolism impairment and t d [ ] [ ] [ ] . despite obesity is usually associated with decreased risk of death in patients with severe acute respiratory distress (obesity paradox), currently available data suggest that an elevated body mass index should be considered as an independent risk factor predisposing to poor prognosis [ ] and death in covid- [ ] [ ] [ ] [ ] . indeed, the prevalence rate of obesity in this cluster of patients has been reported in % of the cases [ ] and a bmi greater than kg/m has been usually observed in patients requiring hospitalization and invasive mechanical ventilation [ ] also in younger patients (< years) [ ] . pathophysiological mechanisms possibly related with poor prognosis in obese patients are not completely understood but may be attributable to a greater inflammatory background as similarly found in dm due to hyperglycaemia and insulin resistance [ ] . obesity is usually associated to other severe comorbidities with high impact on cardio-metabolic health, such as fatty liver disease, vascular inflammation, cardiovascular atherosclerotic diseases and heart failure [ ] that might be related with a higher burden of lethal complications, especially in hospitalized patients with covid- [ ] . in addition to cardiometabolic risk factors, obese patients are more prone to have a decreased pulmonary ventilation or obstructive sleep apnoea, which predispose them to low levels of blood oxygenation at baseline and consequently to worse respiratory outcomes in case of acute infective respiratory diseases [ , ] . nutritional patterns usually exhibited by obese patients are frequently characterized by an elevated dietary consumption of processed food rich in saturated fat, cholesterol, sugar and a low consumption of fibres and micronutrients, such as vitamin d [ ] . these dietary patterns may affect physiological microbiome composition, weaken the immune response against microbial agent and foster immune system dysfunction [ ] . in addition, vitamin d deficiency/insufficiency and sedentary lifestyle, which are highly prevalent among obese patients, should be considered as predisposing factors for worse prognosis in response to acute infections, including covid- [ ] . abdominal obesity usually leads to a low cardiorespiratory reserve and systemic inflammatory dysfunction which predispose to a worse prognosis in covid- [ ] . conversely, regular physical exercise, which is normally lacking in an obesogenic lifestyle, is associated to higher levels of cardiorespiratory fitness, and is believed to improve the innate immune response and attenuate cytokine dysregulation often experienced by high risk patients with the so called cytokine storm [ ] . visceral obesity is also a risk factor for both the development and progression of cardiovascular diseases [ ] considering that it fosters higher level of pro-thrombotic circulating factors and predisposes to thrombotic events [ ] . furthermore, visceral obesity is more prevalent in men than women and this biological phenomenon has been hypothesized to have a putative role in driven poor prognosis of covid- especially in men. from this point of view, male obesity is usually associated with a functional hypogonadism and these clinical conditions are both associated with one other [ ] , according to a complex and multifactorial pathogenesis [ ] that fosters higher baseline levels of inflammation and endothelial dysfunction [ ] . aromatase gene expression is enhanced by prostaglandin e , whose levels were found to be higher in visceral adipose tissue of obese men [ ] . an enhanced aromatase activity at the level of adipose tissue increases local levels of estradiol that is thought to be a defensive mechanism against local inflammation and insulin resistance [ ] . whether augmented aromatase levels (and activity) at the level of adipose tissue in men may be responsible for a systemic testosterone-tooestrogen imbalance remains questionable. however, obese men are usually affected by this biochemical condition and body mass index is inversely correlated to testosterone-to-oestrogen ratio [ ] . a low testosterone-to-estradiol ratio contributes to increase the cardiovascular risk particularly in elderly [ ] and in those with previous cardiovascular diseases [ ] [ ] [ ] . in addition, hormonal pattern associated with visceral obesity may play a relevant role in reducing the efficacy of immune response against infectious agents, predisposing to cytokine dysregulation, endothelial dysfunction, thrombosis, finally driving patients, particularly men, to poor prognosis or death [ ] . moreover, ace is also expressed on adipose cells [ ] and a larger extension of adipose tissue in obese patients may significantly increase the number of available receptors for sars-cov- , thus leading to a much greater viral shedding once the infection occurs [ ] . in conclusion, multiple diabetes-associated chronic comorbidities, particularly obesity, have been found to worsen the prognosis in covid- affected patients by acting as independent risk factors. careful management and prompt interventions are thus required for improve clinical outcome predominantly in type diabetic patients. pathogenetic mechanisms basically involved in sars-cov- infection may be exacerbated by the use of concomitant medications for the management of t d. of note, an exaggerate pulmonary and systemic expression of ace facilitates sars-cov- replication and may be responsible for worse clinical course and poor prognosis [ , ] . in animal model, pioglitazone has demonstrated to increase ace expression particularly at the level of hepatic and adipose tissue [ , ] . on the other hand, the analysis of potential therapeutic targets for sars-cov- assessed by a computational model found pioglitazone to have a potential for inhibiting clpro, an essential target for viral replication [ ] . these findings did not provide conclusive assumption and diabetologists can safely prescribe pioglitazone taking into account general concerns including fluid retention and heart failure [ ] . gliflozins prescription is increasing over time, also considering a long-term beneficial cardiovascular and renal protection [ , ] . many mechanisms of cardiovascular and renal protection have been proposed, including an enhanced induction of ace expression at the level of heart and kidney but it is unclear whether this effect may negatively influence clinical course in covid- [ ] . moreover, despite gliflozins reduce inflammatory injury and endothelial dysfunction, none conclusive data are currently available to confirm their potential beneficial effect in diabetics with covid- [ ] . concerns about gliflozins use in covid- are attributable to volume contraction, renal insufficiency and increased risk of ketoacidosis that may be supposed to occur particularly in hospitalized patients, including those severely ills. dipeptidyl peptidase iv (dpp-iv or cd ) is a transmembrane and soluble ectopeptidase largely expressed in human tissues, including airways, lung and leucocytes [ ] . particularly, dpp-iv is specifically involved in mers pathogenesis given that it mediate mers-cov- internalization in host cells [ ] . no data actually support the role of dpp-iv in the internalization of sars-cov- and further study are needed to verify this aspect, and for demonstrating clear protective effects [ ] . however, dpp-iv inhibitors have shown to potentiate immune response by increasing t-cells survival, consequently enhance immune response [ ] , and possibly playing a relevant role in reducing the onset or progression of acute pulmonary manifestations in covid- [ ] . glucagon-like peptide receptor agonists (glp- ras) belong to an effective class of medications approved for the treatment of t d and for preventing diabetes-related cardiovascular and renal complications over time [ ] [ ] [ ] [ ] . immune response and systemic inflammation play a crucial role in sars-cov- infection, particularly in case of severe clinical course of the disease. in this clinical scenario, it is speculated that the use of glp- ras could provide both a better glucose control and anti-inflammatory effects with consequent improvement of outcomes in covid- affected patients [ ] . in patients with pulmonary inflammation, mononuclear circulating cells express lower level of glp- receptors than controls and this condition is associated with a blunted production of interferon gamma by t cells and nk cells. in addition, the expression of programmed death cell protein , which mediates t-cell apoptosis, is enhanced on t-cell surface and consequently the efficiency of cell-mediated immune response is weaken. liraglutide, a once-daily administered long-acting glp- ra, demonstrated to restore the expression of glp- receptors on macrophage surface, and potentiate immunemediated response [ ] . in addition, both dpp-iv pharmacological inhibition (linagliptin) and glp- ra (liraglutide) were found to contrast pulmonary injury, reduce platelet activation, microvascular thrombosis, and oxidative stress in mice model of endotoxemia [ ] . moreover, glp- ras have been found to reduce the expression of pulmonary il- , thus playing an interesting role in contrasting a il- mediated damage in immune-allergic diseases and viral infections [ ] . considering that pancreatic islets express ace , glucose impairment in covid- diabetic patients could be attributable to a partial insulin deficiency [ ] . however, glucose impairment could also be attributable to sars-cov- infection-induced stress or as the consequence of some medications or treatment protocols, including high-dose glucocorticoids, particularly used in hospitalized patients [ ] . insulin therapy is recommended in hospitalized patients [ ] , including those with covid- , and a basal-bolus respective to a sliding scale regimen should be preferred in infected patients for avoiding glycaemic excursion and greater glucose variability [ , ] . hypertension is frequently observed in t d patients leading to a consistent increase in the risk of atherosclerotic cardiovascular and renal diseases [ ] . ace inhibitors and angiotensin receptor blockers compared to other antihypertensive medications demonstrated to be more effective to prevent or delay the onset of cardiovascular and renal complications in people with t d, and are currently used as the first-line treatment in these patients [ , ] . evidence from animal models suggested that ace inhibitors are able to increase the expression of ace at the level of lung, thus leading to initial clinical concerns about the management of arterial hypertension in diabetic patients [ ] . first suggestions advised to replace these medications with calciumchannel blockers in order to avoid undesirable detrimental effects of covid- clinical course [ ] . nevertheless, no sufficient data supported the hypothesis that the use of renin-angiotensin system blockers may interfere with the internalization of sars-cov- in respiratory cells hence increasing its virulence [ ] . in addition, ace inhibitors and angiotensin receptor blockers protect lung, heart and kidney against inflammation, thus playing a potential beneficial role also in t d patients with covid- [ ] . statins are usually prescribed especially in t d patients to protect against cardiovascular complications [ ] . the role of statins in covid- is not clearly established, however, some observation should be done. first, covid- is associated with higher cardiovascular mortality specifically in patients with more risk factors, including hypertension and t d, and statins could be useful to maintain or optimize lipid management and improve endothelial dysfunction in this clinical setting [ ] . in animal models, statins inhibit the myeloid differentiation primary response (myd ) [ ] . myd is a protein adaptor for inflammatory signalling pathways downstream of members of toll-like receptors and il- receptor families, and plays a critical function in the activation and amplification of innate immune response [ ] . the inhibition of myd seems to reduce pulmonary inflammatory damage, and to improve survival in sars-cov and mers-cov infected mice [ ] . patients with established cardiovascular disease, and those at higher risk of atherosclerotic cardiovascular disease including t d (also in primary prevention) should be advised to maintain current statin treatment also in case of confirmed covid- . in patient with active covid- , an increased risk of muscular damage has been described and statin therapy could be interrupted for a short period of time in order to favour muscular recovery [ ] . t d should be considered as a risk factor for poor prognosis in covid- due to several reasons, including poor baseline glucose control and high glycaemic variability, diabetes-related immune dysfunction and concurrent comorbidities, also proven to act as independent risk factors for poor prognosis in this clinical setting. considering that respiratory system remains essentially the leading way for sars-cov- entering in host, and given that immune barriers are weaken in t d patients, including resident pulmonary macrophages, neutrophils and t cells [ ] , diabetologists could improve clinical outcomes in covid- simply by the use of such a medication with potential for positive immune-modulation and anti-inflammatory effects. unfortunately, inconclusive deductions are currently available for considering concomitant medications favourable (as well as detrimental) factors in covid- patients with t d. despite some putative mechanisms have been identified and some speculative hypothesis have also been formulated indicating that some anti-diabetes medications may improve clinical course in covid- (pioglitazone, gliflozins, dpp-iv inhibitors, glp- ra), further studies are needed to clarify the issue. a timely glucose control should be obtained in diabetic patients during pandemic for the purpose to avoid potentially harmful outcomes in case of sars-cov- infection [ ] . anti-diabetic medications should be used with caution, also considering their impact on patient safety in case of complications related with covid- infection (renal failure, cardio-respiratory burden, ketoacidosis, etc). oral and non-insulin injectable medications (glp- ras) should be considered to maintain or intensify household glucose control, while insulin treatment is currently known to be safer in case of hospitalized and seriously ill patients [ ] . given this consideration, in seriously ill patients, immune response should be adequately monitored in order to carefully predict or precociously diagnose a severe disease [ ] and cytokines, including il- , may be considered as a goal for novel and more specific target therapies particularly in t d individuals [ ] [ ] [ ] . beyond the risks strictly related with covid- infections in diabetic patients, further concerns should be taken into account. social distancing and lockdown have been proposed as the most effective action to prevent and reduce spread of sars-cov- infection [ ] . consequently, more time has been spent in household and access to public and private services has been consistently reduced. thus, several barriers exist for diabetic patients to maintain an adequate fitness status and weight management as well as access to ambulatory care for obtaining adequate treatment adjustments [ ] . in the last few months, home confinement led to physical inactivity and low exposure to sunlight, with possible detrimental effects particularly in diabetic and obese patients [ ] . physical exercise should be encouraged also at home or outdoor, even respecting social distancing rules, since it promotes weight loss, and improves cardiorespiratory fitness [ ] ; reduces levels of cortisol thus reinforcing immune response against infections; induces t-cell differentiation and maturation [ ] . importantly, patients should be advised about risks and supported regarding pandemic-related concerns. particularly, they should be elucidated about general hygienic tips to protect themselves and others from sars-cov- spread; promptly recognize covid- signs and symptoms; access orderly to approved testing if exposed; furthermore, it is important to avoid unnecessary routine appointment in person especially for elderly patients [ ] . closely monitoring of glucose control should be recommended at home and glucose reports should be periodically sent to the diabetologist for proper therapy adjustments [ ] . the hard lesson form lombardy disaster probably teaches to change prospective in the conception of patients care during the present and in case of further pandemic. implementation of community-centred care system (home care and mobile clinics) may result in a prompt detection and better management of infected patients particularly for frail individuals. moreover, it might contain an unnecessary hospital workload, letting hospital activities to focus mainly on acute cares and limiting contagion risks among inpatients and healthcare personnel. finally, it could provide at home special cares for elderly and comorbid 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(american association of clinical endocrinologists at the epicenter of the covid- pandemic and humanitarian crises in italy: changing perspectives on preparation and mitigation. nejm catalyst innovations in care delivery managing diabetes in pregnancy before, during, and after covid- acceptability and utilization of newer technologies and effects on glycemic control in type diabetes: lessons learnt from lockdown patient empowerment using electronic telemonitoring with telephone support in the transition to insulin therapy in adults with type diabetes: observational, pre-post, mixed methods study key: cord- -fl l b authors: daryabor, gholamreza; atashzar, mohamad reza; kabelitz, dieter; meri, seppo; kalantar, kurosh title: the effects of type diabetes mellitus on organ metabolism and the immune system date: - - journal: front immunol doi: . /fimmu. . sha: doc_id: cord_uid: fl l b metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type diabetes mellitus (t dm). the field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and t dm), and metabolic factors, in turn, regulate immune cell functions. obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for t dm. obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. they also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. the impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus (sars-cov- ). thus, the need for a proper immunization protocol among such patients is granted. the focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of t dm patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases. the metabolic syndrome is defined by the presence of metabolic abnormalities such as obesity, dyslipidemia, insulin resistance, and subsequent hyperinsulinemia in an individual ( ) . dyslipidemia, the main characteristic of metabolic syndrome, is defined by decreased serum levels of high-density lipoproteins (hdls) but increased levels of cholesterol, free fatty acids (ffas), triglycerides (tg), vldl, small dense ldl (sdldl), and oxidized ldl (ox-ldl) ( table ) ( ) . individuals with the metabolic syndrome are much more likely to develop type diabetes mellitus (t dm), cardiovascular diseases (cvds), and fatty liver disease ( ) ( ) ( ) . t dm, the most common form of diabetes (∼ %), is characterized by a systemic inflammatory disease accompanied by insulin resistance (ir) or decreased metabolic response to insulin in several tissues, including the adipose tissue, liver, and skeletal muscle, as well as by reduced insulin synthesis by pancreatic beta cells ( , ) . studies on immunometabolism have indicated that the metabolic states and immunological processes are inherently interconnected ( ) . in this scenario, metabolites derived from the host or microbiota regulate immunological responses during health and disease ( ) . accordingly, in obese individuals, expanded adipose tissue at different locations, by initiating and perpetuating the inflammation, induces a chronic low-level inflammatory state that promotes ir ( ). every organ system in human body can be affected by diabetes, but the extent of organ involvement depends largely on the severity and duration of the disease (figure and table ). during the progression of diabetes, hyperglycemia promotes mitochondrial dysfunction and induces the formation of reactive oxygen species (ros) that cause oxidative stress in several tissues such as blood vessels and pancreatic beta cells ( ) ( ) ( ) . accumulating damage to the mitochondria, as well as several macromolecules, including proteins, lipids, and nucleic acids by ros promotes the process of aging ( ) . as a result, pancreatic β cells that require functional mitochondria to maintain insulin synthesis fail to generate high enough levels of insulin ( , ) . in the absence of compensatory mechanisms, stress-responsive intracellular signaling molecules are activated and cellular damage occurs. elevated intracellular levels of ros and subsequent oxidative stress play an important role in the pro-atherosclerotic consequences of diabetes and the development vascular complications ( , ) . moreover, the non-enzymatic covalent attachment of glucose and its toxic derivatives [e.g., glyoxal, methylglyoxal (mgo), and deoxyglucosone] to the biological macromolecules such as nucleic acids, lipids, and proteins leads to the formation of advanced glycation end products (ages) ( , ) . accumulated ages block the insulin signaling pathway and promote inflammation ( , ) . in addition, the attachment of ages to their receptors [e.g., cd , galectin- , scavenger receptors types i (sr-a ), and ii (sr-a )] on the surfaces of immune cells in the circulation and tissues activates the expression of pro-inflammatory cytokines and increases free radical generation ( ) . furthermore, due to the chronic exposure of cells to high glucose levels in untreated t dm patients, glucose toxicity might occur in several organs. this will figure | effects of t dm on body organs. t dm is an inflammatory state that affects circulatory system, gastrointestinal tract, pancreatic beta cells, liver, and skeletal muscles and makes them dysfunctional. nfald, non-alcoholic fatty liver disease; nash, non-alcoholic steatohepatitis; er, endoplasmic reticulum. eventually lead to nephropathy, cardiomyopathy, neuropathy, and retinopathy. gut microbiome dysbiosis is another important factor that can facilitate the induction and progression of metabolic diseases such as t dm ( ) . the gut microbiome dysbiosis, by altering the barrier functions of intestine and the host metabolic status, promotes the insulin resistance in diabetic patients ( ) . diabetes also impairs the immune system and increases the susceptibility of patients to serious and prolonged infections ( ) . this is likely to be the case with the severe acute respiratory syndrome coronavirus (sars-cov- ), as well ( , ) . in the current paper we will review recent research to explore the impairment of body organs in t dm patients and explain how diabetic patients become more susceptible to certain infectious diseases. vascular homeostasis is an important function of the endothelium. under homeostatic conditions, the ecs maintain the integrity of blood vessels, modulate blood flow, deliver nutrients to the underlying tissues, regulate fibrinolysis and coagulation, control platelet adherence and patrol the trafficking of leukocytes (figure a ) ( ) . normal ecs also internalize high-density lipoproteins (hdls) and its main protein part apolipoprotein a-i (apoa-i) in a receptor-mediated manner to activate endothelial cell nitric oxide (enos) synthase and promote anti-inflammatory and antiapoptotic mechanisms ( figure b ) ( ) . hdl receptors on the surfaces of ecs include: the atp-binding cassette (abc) transporters a and g , the scavenger receptor (sr)-b and the ecto-f -atpase ( ) . according to the epidemiological studies, diabetes mellitus is considered as one of the main risk factors for cvd (figure ) ( ) . from the beginning of t dm, the functions of ecs are impaired, which is the main cause of disease-related side-effects ( ) . ecs can initiate and perpetuate the inflammatory milieu during the pathogenesis of diabetes. due to the negative impacts of hyperglycemia and subsequent oxidative stress, cvds are more common among diabetic patients ( ) . it has been observed that incubation of human aortal endothelial cells (haecs) with a medium containing high glucose concentrations (hg, mm) increases the intracellular levels of mgo and glycated proteins that in turn activate the unfolded protein response (upr) and trigger inflammatory and prothrombotic pathways ( ) . glycated apoa-i, which is formed during hyperglycemia, modifies its structure, decreases its lipid-binding ability, prevents cholesterol efflux from macrophages and impairs its anti-inflammatory function ( , ) . vaisar et al. have shown that hdls from diabetic patients have a reduced capacity to trigger enos production and suppress tumor necrosis factor-α (tnf-α)mediated inflammatory responses within ecs ( ) . diseases such as t dm that induce high levels of vascular injury are accompanied by an elevated number of circulating endothelial cells (cecs) ( ) . t dm-related risk factors such as dyslipidemia, hyperglycemia, and hyperinsulinemia as well as other conditions (e.g., inadequate physical activity, smoking, and high blood pressure) facilitate the formation of atherosclerotic plaques/lesions ( ) . dyslipidemia, due to the elevated flux of ffa from insulin-resistant tissues and spillover from entry (c) blood vessels in t dm patients. during the progression of the disease, red blood cells become glycated, while activated ecs synthesize elevated levels of adhesion molecules and chemokines that facilitate monocytes recruitment, adhesion, and transmigration across the endothelium toward the subendothelial region. monocytes are then differentiated into macrophages and eventually, by excess lipid uptake, generate foam cells. subsequently, further immune cell infiltration into the atherosclerotic lesion occurs, where their inflammatory cytokines promote platelet activation, ec apoptosis, and increased generation of ros and ox-ldl. (d) interactions between oxldl and its receptor aggravate ros generation, nf-κb activation and inflammation. ec, endothelial cell; rbc, red blood cell; plt, platelet; hdl, high-density lipoprotein; ox-ldl, oxidized low-density lipoprotein; ros, reactive oxygen species; enos, endothelial nitric oxide synthase; no, nitric oxide; lox- , lectin-type oxidized ldl receptor . into adipocytes, is considered as an important risk factor for developing cvd among diabetic patients. this is because dyslipidemia promotes inflammation, endothelial dysfunction, and platelet hyperactivation ( , ) . during the progression of atherosclerosis, lipids, immune cells, and extracellular matrix accumulate in the arterial intima or subendothelial regions ( figure c ) ( ) . advanced plaques can impede blood flow and cause tissue ischemia or might become disrupted and generate a thrombus that stops the blood flow of important organs. vascular complications of diabetes engage either tiny or large blood vessels (micro-and macroangiopathy, respectively). microangiopathies, which can be seen in the kidneys, vasa nervorum and eye tissues, cause nephropathy, neuropathy, and retinopathy. macroangiopathies, by inducing atherosclerosis in the coronary, carotid, and peripheral arteries, increase the risk of myocardial infarction (mi), stroke and peripheral artery disease (pad). macrovascular complications due to ec dysfunction are considered as an important cause of mortality and morbidity among diabetic patients ( ) . oxidative stress has an essential role in the induction of vascular complications during the course of diabetes ( ) . ec dysfunction (e.g., delayed replication, dysregulated cell cycling, and apoptosis), as well as enhanced ox-ldl formation are some consequences of oxidative stress. it has been well-established that sdldl and ox-ldl have an enhanced atherogenic ability and are more useful biomarkers than total ldl for predicting cvd ( , ) . sdldl particles have a smaller size than other ldl particles. thus, sdldl particles are more easily oxidized, and their atherogenic potential is enhanced. during oxidative stress, levels of ox-ldl increase by the excess action of reactive oxygen species (ros) ( ) . subsequently, ox-ldl interaction with scavenger receptors, including cd , sr-a /cd , sr-b , and lectin-like ox-ldl receptor- (lox- ) on the surface of ecs activates the nadph oxidase that in turn increases the expression of ros and activates the transcription factor nf-αb ( ) . afterwards, the expression of lox- , adhesion molecules (e.g., selectins and integrins) and the secretion of pro-inflammatory cytokines and chemokines are increased, while no synthesis is decreased in ecs ( figure d ) ( ) ( ) ( ) . ec-derived chemokines bind to their cognate receptors on the surfaces of monocytes and recruit them toward the inflamed endothelium. following this, selectin-based rolling and integrin-based attachment of monocytes to the ecs cause their migration toward the subendothelial region, where they develop into lipid-laden macrophages or foam cells later on ( ) . the scavenger receptor lox- plays an important role in the uptake of ox-ldl during atherogenesis. it is strongly expressed on the surfaces of ecs, but has an inducible pattern of expression on the surface of macrophages and smooth muscle cells ( ) . the accelerated uptake of ox-ldl by macrophages accounts for their transformation into foam cells, the initial hallmark of atherosclerosis ( , ) . besides, diabetes leads to both quantitative and qualitative defects in circulating angiogenic progenitor cells (capcs) that take part in the repair of injured endothelium ( ) . it has been shown that humans or mice with decreased numbers of cd + cd + cd + cd dim sca- + flk- + capcs have an increased prevalence of t dm, elevated hba c levels and aggravated cvd risk scores ( , ) . in diabetic patients, despite elevated serum levels of proangiogenic molecules, like angiopoietin- / , epo, and vegf-a, angiogenesis is impaired. this is mainly due to the decreased expression levels of vegfr and cxcr on the surfaces of capcs, which makes them unresponsive to the angiogenic factors ( , ) . it has also been shown that circulating proangiogenic granulocytes composed of eosinophils and neutrophils are also impaired in diabetic patients ( ) . besides, elevated levels of ages in t dm cause ec dysfunction and vascular inflammation ( ) . ren et al. have shown that incubation of human coronary artery endothelial cells (hcaecs) with ages causes decreased expression (at both mrna and protein levels) and enzymatic activity of enos, increased levels of ros, diminished mitochondrial membrane potential and declined activity of catalase and superoxide dismutase in treated cells ( ) . another study by lan et al. has shown that ages in the pancreas decrease ec viability and induce their apoptosis in an nfκb signaling-related manner ( ) . however, apigenin ( ′ , , trihydroxyflavone) can protect ecs against oxidative stress and subsequent inflammatory reactions mediated by ages ( ) . apigenin binds to methylglyoxal (mgo) and forms a complex that inhibits age formation. chettab et al. have shown that the expression of icam- as well as the production of il- , are significantly increased in huvecs cultured in hg medium compared to cells cultured in normal glucose (ng, . mm) conditions ( ). bammert et al. found out that incubation of huvecs with hg media promotes the generation of endothelial microparticles (emps) that, when added to normally cultured huvecs, downregulate the expression of anti-apoptotic microrna mir-let a, but enhance the synthesis of active caspase- and cause cell apoptosis ( ) . several micrornas, including mir- , mir- a, mir- , mir- a, mir- , mir- , mir- a, mir- , and mir-let d, regulate vascular homeostasis. it has been shown that the expressions of mir- a and mir- are significantly reduced in circulating mps isolated from diabetic patients compared with normal individuals. this could be involved in making diabetic individuals more susceptible to coronary heart disease ( ) . moreover, hg media upregulate the expression of nadph oxidase that will induce the generation of ros. this leads to subsequent apoptosis of the huvecs through a ros-dependent caspase- pathway ( ). su et al. have demonstrated that argirein medication, by inactivating nadph oxidase, can prevent endothelial cell apoptosis in a rat model of t dm and hence attenuate vascular dysfunction ( ) . hg further increases the permeability of the huvecs in a protein kinase c (pkc)-dependent manner ( , ) . hassanpour et al. showed that incubation of endothelial progenitor cells with the serum of t dm patients inhibits their migration toward bfgf, increases their expression of vegfr- , but reduces their expression of vegfr- and induces their apoptosis ( ) . however, humanin (hn), a mitochondriumderived peptide, is cytoprotective against apoptosis during pathological conditions, such as diabetes mellitus ( ) . it has been demonstrated that simultaneous incubation of h c cells, a line of rat cardiac myoblasts, with h o and hn decreases the intracellular levels of ros, preserve mitochondrial function/structure and decline cellular apoptosis ( ) . wang et al. have indicated that the treatment of huvecs with hn before their incubation with hg medium increases the expression of enos, while decreasing the expression of endothelin (et- ), vcam- , tnf-α, il- β, and e-selectin in a krüppellike factor (klf )-dependent manner. such changes in the expression of integrins prevent the attachment of monocytes to huvecs ( ) . accordingly, hn might be used to prevent the development of hyperglycemia-associated ec dysfunction in t dm. ec activation and expression of adhesion molecules also facilitate activation and adhesion of platelets. this will increase the risk of thrombosis and promote the development of thrombotic angiopathy, typical for diabetic patients. platelets are tiny anucleated cellular fragments generated from megakaryocytes in the bone marrow. they circulate in the blood for ∼ - days and play essential roles in hemostasis and in controlling vascular integrity ( ) . circulating inactive platelets move in the proximity of vessel walls (figure a ) and rapidly get activated in response to vascular injury. at the end of their life, platelets are cleared from circulation with the action of the liver and spleen-resident macrophages. platelets have an essential role in the initiation and progression of inflammation. platelet hyperactivation that occurs during inflammatory states (e.g., t dm) facilitates the pathogenesis of cvds ( figure c ) ( , ) . it has been shown that elevated levels of resistin, an adipokine, in diabetic patients enhances oxidative stress, promotes endothelial dysfunction and facilitates platelet activation ( ) . activated platelets with an increased mean volume [mean platelet volume (mpv)] secrete microparticles (mps) and soluble adhesion molecules (e.g., sp-selectin and scd l) that in turn activate endothelial and immune cells ( ) ( ) ( ) . higher levels of platelet-derived mps, which correlate positively with fasting blood sugar and glycated hemoglobin, have been shown in newly diagnosed t dm patients compared to healthy individuals ( ) . in t dm patients thrombotic microangiopathies can lead to the development of cvds ( ) . platelets in the patients adhere to ecs and aggregate more rapidly than in healthy individuals thereby increasing the risk of thrombosis. in a mouse model of t dm, zhu et al. have shown that ages interact with cd , a member of the type scavenger receptor family, on the surfaces of murine platelets to activate them and induce a prothrombotic state ( ) . elevated levels of the p y receptor on the surface of platelets in t dm expose diabetic patients to a prothrombotic condition. this receptor has an essential role in platelet activation ( ) . zhou et al. have shown that long non-coding rna (lncrna) metallothionein pseudogene (mt p ), which is markedly upregulated in megakaryocytes of t dm patients, enhances the expression of p y receptor in platelets ( ) . they indicated that this is due to the inhibitory action of mt p on mir- . virtually all parts of the human digestive system, including the gastrointestinal tract, pancreas, and the liver are affected by diabetes. the git is populated with a myriad of microorganisms, including principally bacteria but also archaea, viruses, fungi, and protozoans that dynamically influence the health status and homeostasis of the host. the physiological functions of the git resident microbes improve gut integrity, protect against microbial pathogens and regulate immune responses ( ) . mucosal barriers, such as intestinal epithelial cells (iecs) and the mucus layer, spatially isolate the host immune system and gut microbiota to prevent unnecessary immune activation and intestinal inflammation. they also facilitate the uptake of nutrients through receptors and transporters. however, hyperglycemia, in a glut -dependent manner, can influence the mucus and alter the integrity of adherence and tight junctions between intestinal epithelial cells of diabetic mice. this will enhance the permeability of the intestinal barrier leading to so called "leaky gut." subsequently, hyperglycemia may facilitate the dispersal of an enteric infection into a systemic infection (figure ) ( ) . interestingly, the reversal of hyperglycemia, conditional deletion of glut from the iecs and inhibition of glucose metabolism will fix the barrier dysfunction and prevent the spread of bacteria ( ). xu et al. have shown that faecalibacterium prausnitzii, one of the most frequent commensal bacteria in normal individuals with essential roles in gut homeostasis, generates anti-inflammatory molecules that enhance the expression of tight junctions and improve intestinal integrity during diabetes ( ) . however, in some cases, gut microbiota dysbiosis or altered microbial composition of the intestines could induce t dm and lead to its progression ( ) . of interest, the widely used antidiabetic drug metformin can improve barrier integrity and restore the healthy microbiota composition of the gut in diabetic patients ( ) . the intestinal commensal bacterium akkermansia muciniphila can also act as a sentinel to reduce microbial translocation across the gut and prevent the subsequent inflammation in patients with t dm ( ) . hyperglycemia can further decrease the intracellular levels of glutathione (gsh) but increase inos activity and no production in the iecs ( ). zhao et al. have found out that hyperglycemia in a pkcα-dependent manner inhibits the ubiquitination, internalization and degradation of the divalent metal transporter (dmt ) present on the microvillar membranes of iecs. subsequently, intestinal iron uptake is enhanced and accumulated iron ions aggravate diabetes-related complications and increase mortality ( , ) . the pancreas consists of the exocrine and endocrine compartments. the endocrine part is made of different cell types, including α, β, δ, and ε cells that secrete glucagon, insulin, somatostatin, and ghrelin hormones, respectively. these cells are aggregated into specialized structures called islets of langerhans, which play an important role in controlling blood glucose levels through the secretion of insulin and glucagon. in t dm, despite normal levels of β-cell replication and islet formation, β-cell apoptosis is increased so that the number of cells declines by ∼ % (figure ) ( ) . during the progression of t dm, the insulin-resistant state forces β-cells to compensate for the lack of insulin by elevating its synthesis to restore the normal blood glucose level. however, in severe diabetic patients, β-cell exhaustion, and subsequent persistent hyperglycemia occur ( ) . furthermore, chronic elevated serum levels of free fatty acids, seen in obesity and t dm, induce lipotoxicity in beta-cells and suppress their insulin secretion ability ( ) . to alleviate chronic inflammation, overcome insulin resistance (ir) and to prevent β-cell apoptosis, stem cells or stem cell derivatives such as insulin-producing cells (ipcs) and exosomes have been suggested ( ) ( ) ( ) ( ) . their effects are believed to be mainly due to their anti-inflammatory activities. secretagogin (scgn) is predominantly expressed by pancreatic β-cells protecting their normal functions. scgn also acts as an insulin binding protein to make it more stable, avoid its aggregation, improve its functions and enhance its secretion ( , ) . in t dm patients, due to the islet cell dysfunction and endoplasmic reticulum (er) stress, serum levels of scgn are elevated reflecting stress and dysfunctional islet cells ( ) . moreover, in patients with t dm, islet amyloid polypeptide (iapp or amylin), a peptide hormone and one of the main secretory products of pancreatic β-cells, tends to deposit in the islets of langerhans, form insoluble fibrils and impair secretory functions of β-cells ( ) . iapp is costored with insulin in the secretory granules of pancreatic β cells. in steady-state conditions it regulates food intake, insulin secretion, and glucose metabolism ( ). ribeiro et al. have noted that pancreatic extracellular vesicles (evs) from healthy individuals, but not from t dm patients, directly bind to iapps and prevent amyloid formation within the pancreatic islets ( ) . the authors showed that the altered protein-lipid composition of the evs is the main reason for this discrepancy ( ) . however, chatterjee et al. have shown that β-cells from t dm patients have a dysfunctional proteasome complex that fails to degrade pancreatic iapp, whereby amyloid formation is induced ( ) . furthermore, in t dm patients, lipids accelerate the formation of fibrillary iapp, which aggravates islet cell damage ( ) . dhar et al. have demonstrated that chronic use of mgo in sprague-dawley rats increases the expression of nf-αb, mgo-derived ages and their receptors in pancreatic β cells. mgo can also induce apoptosis of islet β cells, increase fasting plasma glucose levels and impair glucose tolerance ( ) . in t dm patients the plasma level of mgo directly correlates with fasting blood sugar and hba c levels ( ) . bo et al. further showed that mgo in a dose-based manner impairs insulin secretion of pancreatic β-cell lines min and ins- through increased generation of ros and by induction of mitochondrial dysfunction ( ). robertson et al. have found out that elevated levels of ros in pancreatic β-cells inhibit the pancreas duodenum homeobox- (pdx- ) transcription factor that is needed for insulin synthesis ( ) . it has been shown that chronic use of mgo in animals could induce t dm, while simultaneous use of alagebrium, which breaks age compounds, attenuates the disease ( ) . it has also been reported that during the course of diabetes dedifferentiation and conversion of β-cells into αand δ-"like" cells occurs ( ) . in conclusion, the pancreatic β cell function is progressively reduced during the progression of t dm. the liver is by far the most important metabolic organ with essential roles in regulating homeostasis and mediating glucose and lipid metabolism. metabolic activities of the tissue are precisely controlled by the actions of metabolic substrates, including free fatty acids (ffas) and hormones ( ) . t dm patients usually suffer from a chronic liver condition called non-alcoholic fatty liver disease (nafld). it is characterized by steatosis that means ectopic fat storage in hepatocytes and subsequent insulin resistance (figure ) ( ) . lipid accumulation in hepatocytes leads to impaired biogenesis of mir- that facilitates insulin signaling and prevents lipogenesis ( ) . several factors such as obesity, increased serum levels of fatty acids, and insulin resistance can increase the risk of fatty liver disease. p y receptor, through the induction of the c-jun n-terminal kinase (jnk) and prevention of insulin signaling, can promote insulin resistance in hepatocytes in t dm ( ) . in some cases, nafld may progress into an aggressive form of inflammatory fatty liver disease called non-alcoholic steatohepatitis (nash), which might cause liver cirrhosis and organ failure ( ). dang et al. have indicated that exosomes released from the adipose tissues of obese mice due to the smaller mir- - p content can promote insulin resistance in the murine hepatocyte cell line aml (alpha mouse liver ) ( ) . the adipokine visfatin that is released from the adipose tissue of obese individuals has also been shown to activate the pro-inflammatory stat signaling pathway and nf-κb in the human liver cell line hepg and promote their insulin resistant state ( ) . nevertheless, the hepatocyte growth factor (hgf) can alleviate the insulin resistance of hepatocytes and control their triglyceride and cholesterol contents ( ) . skeletal muscle (sm) is the main tissue that releases glucose after insulin stimulation. hence, insulin resistance in sm has a pivotal role in the metabolic dysregulation of t dm. insulin resistance in sm is the primary defect of t dm that facilitates the progression of fatty liver disease, deposition of fat in the liver (figure ) ( ) . skeletal muscle from diabetic patients expresses less genes related to insulin signaling and metabolic pathways, but more apoptosis and immune-related genes ( ) . this inflammatory milieu is mainly due to the proinflammatory actions of obesity-related adipose tissue mediators, which are released into the circulation and promote inflammation within the sm ( ). furthermore, obesity causes intermyocellular and perimuscular adipose tissue expansion that acts like adipose tissue depots to enhance sm inflammation ( ) . it has been shown that human skeletal muscle cells (hsmc), isolated from diabetic patients, after a -h culture generate significantly more tnf-α, il- , il- , il- , monocyte chemotactic protein (mcp)- , growth-related oncogene (gro)-α, and follistatin compared to non-diabetic individuals ( ) . this altered secretion of myokines (e.g., cytokines secreted by sms) is an intrinsic feature of sm during the progression of t dm. in sm, glut- , which is quickly translocated to the cell surface, facilitates glucose uptake in response to insulin hormone as well as muscle contraction. pinto-junior et al. have shown that the use of age-albumin in rats increases the expression of the inflammatory molecule nf-κb within the sm. nf-κb binds to the promoter of the glut- gene and suppresses its expression (at both mrna and protein levels) ( ) . accordingly, glut- levels on the surfaces of sm decrease and subsequently, whole-body ir develops. the immune system is generally classified into two main arms, innate and adaptive (or acquired) immunity. adaptive immunity is mediated by b cells, which produce antibodies and t cells, which are classified into cd + helper cells and cytotoxic cd + cells. a considerable literature has discussed the dysfunctional immune responses in diabetic patients ( table ) ( ) ( ) ( ) ( ) ( ) ( ) . abnormal immune cell activation and subsequent inflammatory environment has an essential role in the progression of t dm ( ) . in this regard, chronic inflammation due mainly to the activation of the myeloid cell lineage (e.g., macrophages and neutrophils), is directly related to the induction of ir ( , ). their numbers are elevated, are larger and more granular, express diminished levels of antioxidant genes but elevated levels of pro-apoptotic and pro-inflammatory genes. complement system attachment of c-type lectin proteins to mannose residues is decreased, lectin pathway is impaired, cd activity is reduced, mac deposition in vascular walls is increased. dendritic cells (dcs) their numbers and activity are reduced. their cholesterol efflux is decreased, generate foam cells, have dysfunctional efferocytosis. are activated, constitutively release nets, produce high levels of mpo, ros, and calprotectin (s a /a ), are more susceptible to apoptosis, their migration, phagocytosis and microbial killing are impaired. nk cells their numbers are increased but are usually dysfunctional, express high levels of glut but decreased levels of nkg d and nkp , have reduced degranulation capacity, are more susceptible to apoptosis. nkt cells their numbers are increased, produce high levels of ifn-γ, il- , and il- , express high levels of nkp , nkg d, and nkp but low levels of nkg a and b. innate lymphoid cells (ilcs) ilc s are increased and produce high levels of ifn-γ. humoral immunity (b cells) germinal centers are reduced, ab production and isotype switching is defective, abs become glycated, abs fail to activate complement. functions of osteoclasts, which are bone-resident innate immune cells ( ) . this may affect bone structure and delay bone healing. defects in the innate, as well as adaptive immunity, are supposed to be the main cause of diabetic individuals' susceptibility to infections ( ) . furthermore, some microorganisms, especially bacteria, in hyperglycemic conditions are better nourished and become more virulent, while also having a better milieu to cause infections. complement system the complement system is a first-line defense mechanism against invading microorganisms. it acts via different but interconnected classical, alternative, and lectin pathways ( ) . ilyas et al. have shown that under high glucose conditions, the attachment of ctype lectin proteins to high-mannose containing glycoproteins is substantially decreased in a dose-dependent manner. these carbohydrate-binding proteins include mannose-binding lectin (mbl), surfactant protein d (sp-d), dendritic cell-specific intercellular adhesion molecule- -grabbing non-integrin (dc-sign, cd ), and dc-sign-related (dc-signr) protein ( ) . reduced binding of mbl in the presence of high levels of sugar causes a significant reduction in the lectin pathway activity, but does not influence classical or alternative pathway activity ( ) . nevertheless, barkai et al. did not find significant differences in the function of classical or mbl pathways between t dm and healthy individuals ( ) . however, significantly decreased activity of ficolin- -mediated lectin and alternative pathways, as well as decreased levels of c d and soluble complement c b- (sc b- ) were seen in diabetic patients with escherichia coli-mediated urinary tract infections ( ) . this may be linked to a reduced ability of diabetics to protect themselves against bacterial infections. the lipopolysaccharides of certain gram-negative bacteria, like salmonella serotype o , as well as the cell walls of fungi, are rich in mannose. possibly, because of this, in addition to additional provision of nutrients, an increased prevalence of fungal infections is seen in t dm patients ( , ) . patel et al. found a significantly higher prevalence of oral candida carriage in diabetic patients compared to healthy controls ( ) . they found that candida albicans was the most commonly isolated species followed by c. tropicalis, but uncommon species such as c. lusitaniae and c. lipolytica were also isolated ( ) . another study by jhugroo et al. showed that c. albicans is the predominant yeast isolated from oral mucosal lesions of diabetic patients, followed by. c. tropicalis and c. krusei dendritic cells (dcs) are a heterogeneous population of specialized and professional antigen-presenting cells (apcs) that create a crucial link between the innate and adaptive immune responses ( , ) . some studies have shown that the numbers of dcs are reduced in both type and diabetes ( , ). seifarth et al. have found that t dm patients with poor metabolic control have decreased numbers of both myeloid and plasmacytoid dcs compared with healthy controls. this could make them more susceptible to opportunistic infections ( ) . in the case of good blood glucose control, the reduction in dc numbers was less prominent but still significant, especially for myeloid dc (mdc ) cells ( ) . another study by blank et al. demonstrated that women with t dm and poor glycemic control (hba c ≥ %) have fewer numbers of circulating plasmacytoid dcs (pdcs) compared to diabetic women with good glycemic control (hba c < %) or to healthy women ( ). montani et al. have recently shown that hyperglycemic medium and hyperglycemic sera derived from t dm patients prevent the maturation of monocytes into effective dcs and their activation in vitro ( ) . interestingly, quercetin, a flavonoid with antiinflammatory and antioxidant characteristics, prevented such effects ( ) . macrophages are important immune cells that play critical roles through all stages of the pathogenesis of t dmrelated atherosclerosis ( ). swirski et al. have shown a significantly elevated number of pro-inflammatory monocytes in the circulation of apoe −/− mice, an animal model of atherosclerosis, compared to control mice ( ) . modifications of the lipoproteins in the arterial walls of diabetic individuals make them pro-inflammatory and activate the overlying endothelium. in response, monocytes are recruited into the subendothelial region, differentiate into macrophages and internalize the accumulated lipoproteins. finally, cholesterol-laden foam cells are generated. they promote inflammation and progression of the disease through the synthesis and secretion of cytokines, chemokines, ros, and matrix metalloproteinases (mmps) (figure c ) ( ) . foam cells lose their migratory potential, die by apoptosis and generate a necrotic core within the atherosclerotic plaque ( ) . it has been demonstrated that the use of mesenchymal stem cells in apoe −/− mice reduces the numbers of monocytes/macrophages at the site of inflammation, decreases lipid deposition and diminishes plaque size ( ). ma et al. have studied the effects of long-term hyperglycemia in diabetic mice and found out that compared to non-diabetic control mice, the numbers of f / + macrophages isolated from spleen (spms), as well as from peritoneal exudates (pems) of diabetic mice are significantly decreased ( ) . subsequently, sun et al. showed that stimulation of pems from diabetic mice in vitro with ifn-γ and lipopolysaccharide (lps) significantly decreased the expression of intercellular adhesion molecule (icam- or cd ), cd , tnf-α, and il- , while it increased the production of nitric oxide (no) ( ) . they further showed that stimulation of pems isolated from diabetic mice with il- caused an enhanced arginase activity ( ) . kousathana et al. have demonstrated that circulating monocytes isolated from diabetic patients produce higher levels il- , while having an impaired activation of the nlrp inflammasome and subsequently reduced il- β production ( ) . however, they showed that proper glycemic control would restore such modifications. poor inflammatory responses in circulating monocytes, as well as in macrophages, are responsible for elevated susceptibility to infections and their severity in patients with t dm. macrophages play a critical role in tissue repair. early in wound healing, they are pro-inflammatory to clear pathogens and debris but later, they resolve inflammation and promote tissue repair. in pathological conditions, failure to transform from pro-inflammatory to the anti-inflammatory proliferative phase can cause chronic inflammation in the affected tissue ( ). have shown that an impaired wound healing process in animals with t dm is due to high levels of nlrp inflammasome activity, which promotes the generation of il- β and il- in macrophages ( , ) . efficient skin wound healing process is mediated by the up-regulation of the peroxisome proliferatoractivated receptor (ppar)-γ in macrophages that convert their pro-inflammatory phenotype into healing-related. pparγ suppresses cytokine production by macrophages and hence is upregulated in inflamed tissue-resident macrophages. however, in t dm, pparγ expression is down-regulated in skin-resident macrophages that enhance the activity of nlrp- inflammasome and cause chronic inflammation. using myeloid-specific pparγ −/− mice, it has been shown that the absence of ppar-γ in macrophages is sufficient to delay the healing process and extend tissue inflammation ( ) . in t dm patients, chronic hyperglycemia and hyperlipidemia trigger the secretion of a damage-associated s a molecule (calgranulin a) from pancreatic islets that in turn increase macrophage infiltration ( ) . westwell-roper et al. have shown that iapp aggregates in t dm patients polarize islet-resident macrophages toward the m -like f / + cd b + cd c + phenotype that produces pro-inflammatory cytokines, including tnf-α, il- β, and il- . furthermore, m cells promote islet inflammation, cause β-cell malfunction and apoptosis ( ) . in t dm, excess phagocytosis of apoptotic β-cells by macrophages induces their lysosomal permeabilization, generation of ros, inflammasome activation, and pro-inflammatory cytokines secretion ( ) . collectively, these observations reveal that the functions and plasticity of macrophages are compromised during the progression of t dm. neutrophils are the most prevalent circulating leukocytes and one of the main components of innate immunity. they are recruited to the sites of infection through chemotaxis following complement activation, most importantly by c a. activated neutrophils bind via their surface receptors to induced ligands on the surfaces of inflamed endothelial cells to migrate to tissues. there they phagocytose and kill invading microbes with lysosomal enzymes, antimicrobial peptides and by the generation of ros ( ). neutrophils from patients with t dm, but not from healthy individuals, are activated and produce elevated levels of ros. so, it could increase the risk of random organ injury ( ) . in diabetic patients, the plasma levels of homocysteine are elevated, which is mainly due to its impaired clearance rate ( ) . this will induce neutrophils to constitutively release neutrophil extracellular traps (nets) that can cause vascular damage and delays in wound healing ( , ) . it has been shown that the circulating level of hydrogen sulfide (h s) is significantly reduced in fasting blood of patients with t dm compared with healthy individuals as well as in streptozotocin-induced diabetic rats compared with controls ( ) . h s is produced from cysteine by the action of several enzymes. it acts as a regulator of cell signaling and homeostasis ( ) . it is essential to maintain balanced levels of antioxidants and protect tissues from oxidative stress ( ) . the use of h s or the endogenous l-cysteine in vitro blocks the production of il- and monocyte chemoattractant protein- (mcp- ) in the human u monocyte cell line incubated in high-glucose medium ( ) . yang et al. have shown that h s treatment decreases netosis and enhances the healing process of diabetic wounds by preventing ros-dependent erk / and p activation ( ) . it has been shown that the levels of net components, including histones, elastase and proteinase- , are elevated in the sera from patients with diabetic foot ulcers ( ) . wang et al. have recently indicated that hg dramatically enhances nadph oxidasedependent net generation in diabetic rats and humans. it was proposed that this could have a role in the induction of diabetic retinopathy ( ) . indeed, patients with t dm have elevated plasma levels of mgo, which can induce the production of proinflammatory cytokines like tnf-α, il- , and il- by neutrophils and make them more susceptible to apoptosis ( ) . myeloperoxidase (mpo), which is abundantly produced by neutrophils, but only to a small extent by monocytes and macrophages, might be useful as an early biomarker of inflammation in diabetic individuals ( ) . binding of mpo to endothelial cells increases its half-life. thereby, more proinflammatory oxidant hypochloric acid (hclo) is generated that extends the damage to blood vessels ( ) . in t dm patients, neutrophil activities, including migration, phagocytosis and microbial killing are impaired. this makes diabetic individuals more susceptible to infections ( ) . it has been welldocumented that neutrophils isolated in animal models of t dm have an impaired tlr signaling pathway. this is reflected as a diminished cytokine and chemokine production, possibly as a consequence of reduced phosphorylation of nfκb and iκbα ( ) . the half-life of these neutrophils as well as their in vivo migration and myeloperoxidase activity are decreased. during hyperglycemia, neutrophils produce calprotectin (s a /a ), which interacts with the receptor for advanced glycation end products (rage) on the surface of hepatic kupffer cells and promotes the synthesis of il- ( ). subsequently, il- stimulates hepatocytes to increase the generation of thrombopoietin that in turn attaches to its receptor on the surfaces of bone marrow precursor cells and megakaryocytes to enhance their proliferation and expansion. this results in reticulated thrombocytosis, which means elevated megakaryocyte activity and thrombopoiesis. interestingly, diabetes-related thrombocytosis and subsequent atherothrombosis can be reduced by lowering blood glucose, depleting kupffer cells or neutrophils or by preventing the binding of s a /a to rage using paquinimod ( ) . thom et al. have shown that the incubation of human and murine neutrophils with hg medium would cause their cytoskeletal and membrane instability. this will induce the generation of . to µm diameter microparticles and activate the nlrp inflammasome ( ) . microparticles, which are potently pro-inflammatory, are found in the circulation of healthy individuals, but their generation is increased during cell activation in several diseases, including t dm and cardiovascular diseases ( , ) . furthermore, serum levels of soluble fasl (sfasl) are increased in patients with t dm thereby activating neutrophils and aggravating the inflammatory milieu ( , ) . the proinflammatory roles of sfasl are mediated through increased amounts or activity of nfκb, il- β, caspase- , cd b/cd , and ros ( ) . caspase- activation prevents the sfasl-dependent apoptosis of neutrophils and inhibits their expression of fas and caspase- ( ) . accordingly, hyperglycemia disturbs the normal functions of neutrophils and increases the susceptibility to infections by pathogenic microorganisms. the expression level of nkg d is negatively correlated with hba c levels implying that chronic hyperglycemia would cause nk cell dysfunction ( ) . also, hyperglycemia increases the expression of unfolded protein response (upr) genes in nk cells and induces their apoptosis ( ) . nkt cells express simultaneously markers of both t cells (tcr and cd ) and nk cells [cd , cd , cd (nkg d), and cd (nkp )]. nkt cell subsets produce a broad range of cytokines, including gm-csf, ifn-γ, tnf-α, il- , il- , il- , il- , il- , il- , il- , and il- ( ) . they recognize lipids and glycolipids presented by cd d molecules. phoksawat et al. have shown that the frequency of cd + cd + cd null cd + nkg d hi nkt cells, which produce high levels of il- , are increased in diabetic patients and their numbers are directly correlated with hba c levels ( , ) . lv et al. have recently shown that the numbers of cd + cd + nkt cells are higher in diabetic patients compared to healthy individuals ( ) . they further showed that such cells are mostly cd + , produce elevated levels of ifn-γ and il- and express high levels of nkp , nkg d, and nkp but low levels of inhibitory receptors nkg a and b ( ) . the co-culture of these cells with huvecs significantly decreased their proliferation and migration abilities that were mainly il- dependent ( ) . taken together these studies show that diabetic individuals appear to have elevated levels of inflammationpromoting nkt cells. ilcs are critical effectors of innate immunity that produce both regulatory and pro-inflammatory cytokines to promote tissue repair, immunity, and inflammation ( ) . mature ilcs lack the tcrs. based on their cell surface markers, cytokine production as well as expression of transcription factors the ilcs are classified into types , , and ( ) . these correspond to the different types of cd + t helper cells: th , th , and th , respectively. ifn-γ is the cytokine signature of ilc s, while type cytokines (e.g., il- and il- ) are mainly produced by ilc s and the main product of ilc s are il- and il- . regarding transcription factors, t-bet is mainly expressed by ilc s, gata and rorα are mostly expressed by ilc s and rorγt is predominantly expressed by ilc ( ) . in t dm, the numbers of circulating as well as adipose tissue-resident ilc s are increased compared with normal individuals ( , ) . the frequency of circulating ilc s is positively correlated with fasting plasma glucose (fpg), hba c, homeostasis model assessment for insulin resistance (homa-ir), serum-free fatty acids (ffas) and adipose tissue insulin resistance index (adipo-ir) ( , ) . it has also been shown that patients with increased numbers of ilc have an elevated risk of developing t dm ( ) . a study by wang et al. indicated that adipose tissue-resident ilc s, via the production of ifn-γ, promote tissue fibrosis and induce diabetes in obese individuals ( ) . liu et al. have demonstrated that the numbers of ilc s as well as serum cytokine levels of il- , il- , and il- are significantly elevated in diabetic kidney disease patients and have a positive correlation with disease severity ( ) . they further demonstrated that ilc s, through the tgf-β signaling pathway, are involved in renal fibrosis seen in diabetic kidney disease ( ) . however, galle-treger et al. indicated that the engagement of the glucocorticoid-induced tumor necrosis factor receptor (gitr/or tnfrsf ) on the surface of activated ilc s promotes their secretion of il- and il- , ameliorates glucose homeostasis, protects against the onset of and improves established insulin resistance ( ) . the protective role of ilc s during acute metabolic stress has also been well-documented by dalmas et al. ( ) . humoral immunity (b cells) elevated levels of blood glucose generate covalent sugar adducts with several proteins through non-enzymatic glycation. this can impair humoral immunity in many ways, e.g., by modifying the structure and functions of immunoglobulins (igs) ( ) ( ) ( ) ( ) ( ) ( ) . such modifications in the structure of igs can be determined using matrix-assisted laser desorption ionization (maldi) mass spectrometry ( , ) . the molecular mass of igs in diabetic patients is higher than in normal subjects ( ) . this can lead to reduced efficiency of vaccines that stimulate humoral immunity in these patients. it has been shown that immunization with influenza (flu) vaccines in diabetic patients induces normal or even elevated levels of flu-specific antibodies compared with normal individuals ( ) ( ) ( ) ( ) . however, the ability of the dysfunctional glycated antibodies to neutralize viruses is impaired, which will increase the susceptibility to infections. farnsworth et al. have shown that in t dm, class switch defects in the assembly of antibody genes are also present ( ) . in a model system, mice with t dm have decreased amounts of specific anti-staphylococcus aureus antibodies (total as well as igg), which will increase the risk of infection and morbidity of diabetic mice. however, the levels of igm were elevated, but inefficient in protecting against infection, possibly because of their inability to directly promote phagocytosis. in another study, farnsworth et al. have demonstrated that defects in humoral immunity, as shown by decreased levels of total igg and anti-staphylococcus aureus antibody, aggravate foot infections in a murine model of t dm ( ) . this was due to a reduced germinal center induction and decreased numbers of t and blymphocytes within the germinal centers. this causes failures in antibody generation and class-switch recombination ( ) . mathews et al. have shown that the protective levels of antibodies against streptococcus pneumoniae surface protein a are lower in diabetic patients compared to non-diabetic individuals. these antibodies also have a reduced potential to trigger complement activation on the surface of pneumococci, whereby phagocytosis of the bacteria becomes compromised ( ) . they showed that hyperglycemia reduces both the antibody titers as well as the ability to deposit complement on the bacteria. the abovementioned changes in the ability to protect against s. aureus and s. pneumoniae are important, because these bacteria belong to the most common infection-causing pathogens in diabetic patients. another major group is constituted by gram-negative bacteria that commonly cause e.g., urinary tract infections. many studies have shown that t-cell functions are impaired in individuals with t dm ( ) ( ) ( ) ( ) . elevated levels of activated cd + cd + t helper cells, cytotoxic t-cells, and th cells have been observed in obese diabetic patients compared to nonobese ones ( , ) . nevertheless, pbmcs isolated from obese diabetic patients produced smaller amounts of il- , il- , and tnf-α after stimulation with phytohemagglutinin (pha) ( ) . martinez et al. indicated that diabetic patients have reduced pathogen-specific memory th responses as well as decreased numbers of cd + t cells in response to stimulation with streptococcus pneumoniae ( ) . th cells are critical for the recruitment of neutrophils to the infection site and improve the phagocytosis of invading bacteria and yeast ( ) . moura et al. have shown that diabetic patients, particularly those with foot ulcers, have reduced levels of naive t-cells, but an elevated number of effector t cells and a reduction in the tcr-vβ repertoire diversity ( ) . the observed changes are mainly due to an abnormal amount of inflammatory cytokines (e.g., ifn-γ and tnf-α) produced during infection and to subsequent robust stimulation of t-cells. leung et al. have reported that ischemic tissues of t dm patients contain elevated numbers of tnf-α and ifn-γ producing th cells but diminished numbers of regulatory t cells (tregs), which suppress angiogenesis and decrease vascular density ( ) . the high rate of infectious diseases in t dm patients might also be linked to a reduction in the mitochondrial dna function that causes downstream lymphocyte dysfunction and subsequently increased susceptibility to infection ( ) ( ) ( ) ( ) . in support, we have recently shown that the numbers of ifn-γ producing cells against cytomegalovirus (cmv), epstein-barr virus (ebv), and influenza virus are fewer in t dm patients compared to normal controls ( ) . kumar et al. have also investigated the functions of cd + t cells and nk cells in the whole blood of t dm patients infected with mycobacterium tuberculosis (m.tb). compared to controls, the patients exhibited a reduction in cytokine production (ifn-γ, il- , il- a/f, and tnf-α) and decreased expression of cytotoxic molecules (perforin, granzyme b, and cd a) ( , ) . these studies conclude that the functions of both cd + and cd + t-cell are defective in t dm patients. t dm is usually associated with an elevated risk of asymptomatic bacteriuria, urinary tract infections (utis), pyelonephritis and non-sexually transmitted genital infections, such as balanitis and vulvovaginal infections ( ) ( ) ( ) . the incidence of infections with a complicated course is significantly higher in diabetic patients compared to healthy controls ( table ) . it seems that it is principally defects in the innate immune responses of diabetic individuals that are responsible for the increased susceptibility and prevalence of infections ( , ( , ) cd + tcells mycobacterium tuberculosis ( , ) susceptible to the causative pathogen of lyme disease, borrelia burgdorferi ( ) . the disease is mainly due to the ability of the bacteria to escape complement opsonization and attack, which leads to an impaired uptake and killing of bacteria by neutrophils ( ) . neutrophil dysfunction also increases the susceptibility of diabetic animals to staphylococcus aureus ( ) ( ) . during the progression of t dm in human subjects, the basal phenotype of macrophages is altered so their capacity to control mycobacterium tuberculosis is diminished ( ) . martinez et al. have indicated that alveolar macrophages isolated from diabetic mice express decreased levels of macrophage receptor with collagenous structure (marco) and cd that are engaged in the recognition of trehalose , '-dimycolate, a bacterial cell wall component ( ) . diabetes increases the severity of tuberculosis (tb) and enhances the risk of progression to the active form in latent infections ( , ) . diabetic tb patients have elevated frequencies of th and th cells as well as increased serum levels of inflammatory cytokines, including ifn-γ, tnf-α, il- β, il- , il- , il- a, and il- but decreased levels of il- compared to non-diabetic tb patients. this can contribute to dysfunctional immune responses and poor immune control of a tb infection ( ) . a positive correlation between the serum levels of ifn-γ, tnf-α, il- , and il- a with hb-a c levels was also observed. this indicates an association between impaired control of diabetes and the proinflammatory milieu. tripathi et al. have demonstrated that serum levels of il- were significantly decreased in tb-infected t dm mice and humans compared to non-diabetic tb-infected mice and humans ( ) . they revealed that the treatment of tb-infected diabetic mice with recombinant il- or ilc s (cellular source of il- ) increased the survival of mice, prevented the accumulation of neutrophils near alveoli, diminished the generation of neutrophil elastase (ela ) and prevented epithelial cell damage ( ) . tan et al. have shown that b. pseudomallei and m. tuberculosisinfected pbmcs of diabetic patients fail to produce il- . this leads to a decreased ifn-γ production, poor bacterial killing and elevated intracellular bacterial loads ( ) . an impaired il- production is mainly due to decreased intracellular glutathione (gsh) concentrations within the infected cells of diabetic individuals ( ) . such a combination of an inflammatory microenvironment and dysfunctional immune responses enhances the bacterial load and can subsequently amplify lung injury and fibrosis in diabetic tb patients. chellan et al. have further shown that infections caused by enterococcus faecalis, staphylococcus aureus, and pseudomonas aeruginosa are more prevalent in the wounds of diabetic patients ( ) . t dm patients are more susceptible to utis caused by antibioticresistant escherichia coli, proteus spp., klebsiella spp., coagulasenegative staphylococci, enterobacter spp., and enterococci ( , ) . diabetic patients are also more susceptible to helicobacter pylori (h. pylori) infections ( ). cui et al. have recently reported that t dm patients have an increased risk of infection with kaposi's sarcoma-associated herpesvirus (kshv or hhv- ) ( ) . they further showed that the viral load and antibody titers are positively correlated with blood glucose levels ( ) . diabetic patients also have been shown to have an increased risk of infection with the severe acute respiratory syndrome coronavirus (sars-cov) ( ( ) . the influenza virus that usually causes self-limiting infections can induce severe forms of the disease in diabetic patients ( , ) . following the h n influenza pandemic, diabetic individuals suffered from more severe infections compared to non-diabetic people ( , ) . diabetic patients have also a higher prevalence of chronic cytomegalovirus (cmv), herpes simplex virus (especially hsv- ), and varicellazoster virus infections ( ) ( ) ( ) . accordingly, it seems that the immune response against viruses is impaired in diabetics, and these patients need more care during viral infections. coronavirus virions are enveloped positive-strand rna spherical viruses with a diameter of ∼ nm characterized by spike proteins projecting from their surface and with an unusual large rna genome ( ) . the spike (s) protein of the virus binds to its receptor on the surface of cells by which intracellular proteases are induced ( ) ( ) ( ) . subsequently, the s protein priming and cleavage occurs that allow viral fusion to the plasma membrane and entrance of viral genome into the cells ( ) . sars-cov and sars-cov- use angiotensin-converting enzyme (ace ) as their receptor while mers-cov uses dipeptidyl peptidase- (dpp ) to enter the cells ( , ) . ace is strongly expressed in blood vessels, pancreas, intestine, brain, lungs, heart, and testis ( ) . interestingly, nasal epithelial cells, especially goblet, and ciliated cells express the highest levels of ace and the intracellular protease transmembrane serine protease (tmprss ) that facilitates the entrance of the sars-cov- ( ) . furthermore, the expression of ace is significantly up-regulated in diabetic patients and those treated with ace inhibitors ( ) . coronaviruses cause respiratory, enteric and central nervous system (cns) diseases in various animal species except rats and mice ( ) . most coronavirus infections are mild, but major outbreaks of deadly pneumonia have been caused by sars-cov, mers-cov, and sars-cov- in , , and - , respectively ( ) . on march , , the world health organization (who) announced the pandemic of sars-cov- , the etiologic agent of coronavirus disease- (covid- ) ( ) . the novel coronavirus pandemic, which has emanated from wuhan, china, promotes symptoms similar to those caused by the sars-cov outbreak in . the viral pandemic, which has put the world on alert, has caused over . × confirmed human cases and at least × deaths throughout the world (https://www.worldometers.info/coronavirus/) by june , . most of the infected people experience only mild to moderate respiratory disease and recover soon without the need for special treatment. however, aged individuals and those with health problems, including diabetes, obesity, cardiovascular disease (cvd), hypertension, immune deficiency, and chronic respiratory disease are more likely to develop serious illness (https://www.who.int/health-topics/coronavirus#tab= tab_ ). patients death is mainly due to the acute respiratory distress syndrome, disseminated intravascular coagulation, hemorrhage, coagulopathy, acute organ (e.g., kidney, heart, liver) injury, multi-organ failure, and secondary bacterial infections ( ) . elevated levels of adipose-tissue derived adipokines, interferon, and tnf-α in diabetic patients may impair immune-responses against sars-cov- ( , ) . it has been shown that diabetic patients have impaired clearance of sars-cov- from their circulation ( ) . accordingly, diabetic patients due to the diminished viral clearance, impaired t cell function, and accompanied cardiovascular disease are more susceptible to the coronaviruses infection and subsequent cytokine release syndrome (crs) ( , ) . in support, elevated levels of il- β, il- , il- , il- , il- , il- , ifn-γ, interferon gamma-induced protein (ip- ), granulocyte colony-stimulating factor (g-csf), macrophage inflammatory protein α (mip α), serum ferritin, fibrinogen, plasminogen, c-reactive protein (crp), and d-dimer have been observed in patients with covid- ( , , , ) . covid- patients, especially those requiring intensive care unit (icu) have decreased total lymphocytes (lymphopenia), t cells (both cd + and cd +), b cells, and nk cells ( , ) . it should be noted that most of the surviving t cells in such patients have an exhausted phenotype ( ) . consequently, disease severity is mainly because of the host immune response to viral infection. current evidence about the relationship between pathophysiological mechanisms of diabetes and covid- are limited and further research is still needed. patients with t dm have an elevated risk of infection with plasmodium falciparum ( ) , toxoplasma gondii ( ), opisthorchis viverrini ( ), strongyloides stercoralis ( ), cryptosporidium parvum ( ), blastocystis hominis ( ), ascaris lumbricoides ( , , ) , and giardia lamblia ( ) . interestingly, diabetic patients who were treated with metformin had less p. falciparum infections compared to untreated patients ( ) . omaña-molina et al. have shown that in a mouse model of t dm the animals have an increased susceptibility to granulomatous amoebic encephalitis (gae) caused by trophozoites of acanthamoeba culbertsoni ( ) . the possible reasons for the increased risk of diabetics for parasitic infections are metabolic abnormalities and immune dysregulation. chellan et al. have shown a higher prevalence of fungal infections in the wounds of diabetic patients ( ) . the prevalence correlated with the levels of hba c. the most widely observed fungal isolates were c. albicans, candida parapsilosis, c. tropicalis, trichosporon asahii, and aspergillus species. some of them were resistant to antifungal medications ( ) . al mubarak et al. have also demonstrated that diabetic patients with periodontitis are more susceptible to infection with c. albicans, c. dubliniensis, c. tropicalis, and c. glabrata ( ) . the incidence of candidiasis was significantly increased in patients over the age of with hba c > ( ). it has also been shown that diabetic patients are more susceptible to utis caused by c. albicans ( ) . hyperglycemia impairs the normal functions of the circulatory system, gastrointestinal tract, pancreatic beta cells, liver as well as of skeletal muscles to boost systemic insulin resistance. a hyperglycemic environment also leads to immune cells dysfunction. it increases intestinal permeability, which subsequently enhances the risk of infections in t dm patients. accordingly, further research is still needed to find missing links between impaired physiological/immunological mechanisms and increased susceptibility to infections in t dm patients. the information would be important for better therapy and the design of much more effective vaccination strategies in diabetic patients. gd 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intestinal parasitosis and associated factors among diabetic patients attending arba minch hospital, southern ethiopia intestinal parasitic infections in patients with diabetes mellitus: a case-control study intestinal parasitic infections among diabetes mellitus patients host-parasite interactions in individuals with type and diabetes result in higher frequency of ascaris lumbricoides and giardia lamblia in type diabetic individuals type diabetes mellitus balb/c mice are more susceptible to granulomatous amoebic encephalitis: immunohistochemical study the prevalence of oral candida infections in periodontitis patients with type diabetes mellitus the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.copyright © daryabor, atashzar, kabelitz, meri and kalantar. this is an open-access article distributed under the terms of the creative commons attribution license (cc by). the use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. no use, distribution or reproduction is permitted which does not comply with these terms. key: cord- - m nnufu authors: ceriello, antonio; standl, eberhard; catrinoiu, doina; itzhak, baruch; lalic, nebojsa m.; rahelic, dario; schnell, oliver; Škrha, jan; valensi, paul title: issues for the management of people with diabetes and covid- in icu date: - - journal: cardiovasc diabetol doi: . /s - - - sha: doc_id: cord_uid: m nnufu in the pandemic “corona virus disease ” (covid- ) people with diabetes have a high risk to require icu admission. the management of diabetes in intensive care unit is always challenging, however, when diabetes is present in covid- the situation seems even more complicated. an optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. in this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. no evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of angiotensin-converting-enzyme- (ace ) receptor, which is used by “severe acute respiratory syndrome coronavirus (sars-cov- ) to penetrate into the cells. a real issue is the usefulness of several biomarkers, which have been suggested to be measured during the covid- . n-terminal-pro-brain natriuretic-peptide, d-dimer and hs-troponin are often increased in diabetes. their meaning in the case of diabetes and covid- should be therefore very carefully evaluated. even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act. in the pandemic "corona virus disease " (covid- ) people with diabetes have a high risk to require icu admission. the management of diabetes in intensive care unit is always challenging, however, when diabetes is present in covid- the situation seems even more complicated. this article discusses the specific problems of managing people with diabetes and covid- in icu. in the recent corona virus disease (covid- ) pandemic people with diabetes are paying a very high price. probably they are not exposed to higher risk of being infected, however, in the case, particularly when the metabolic control is not sufficient, they are more prone to serious complications and to die [ ] [ ] [ ] [ ] [ ] . the rates of severe disease are significantly higher in patients with diabetes compared with non-diabetes ( . % vs. . ) [ ] . similarly, type diabetic patients have higher rates of need for intensive care unit (icu), ( . % vs. . %) [ ] . it is well recognized that the management of people with diabetes in an icu is particularly challenging [ ] . to this situation we have to add that diabetes is very often accompanied by co-morbidities, such as cardiovascular disease, hypertension and obesity, which by themselves worsen the prognosis of people with covid- [ ] [ ] [ ] [ ] [ ] . moreover, there are also several other conditions (described in the course of the article), commonly present in diabetes, which can expose people with diabetes open access cardiovascular diabetology *correspondence: antonio.ceriello@hotmail.it irccs multimedica, via gaudenzio fantoli, / , milan, italy full list of author information is available at the end of the article and covid- at high risk for complications. it seems, therefore, quite clear that people with diabetes may have a particular profile/needs when hospitalized in icu for the covid- . in this article we seek to discuss the specific issues to which people with diabetes can be exposed in icu when having the covid- . it is well recognized that an optimal glycemic control during the stay in icu can improve the prognosis [ ] . however, the optimal glycemic control, particularly in icu involves today several aspects. unfortunately, it is not surprising that patients suffering from covid- with hyperglycemia may have a higher risk and a poorer outcome compared with those with euglycemia [ ] . in particular, very recent reports from the usa have shown that uncontrolled glycemia is exposing people with diabetes and covid- at a very high risk to develop serious complications or to die [ , ] . evidence shows that in icu the more time the patients spend in the normal range of glycemia, the better is their prognosis [ , ] . this is also the case of covid- . it has been reported that a tight glycemic control with insulin infusion had a lower risk of severe disease than patients without insulin infusion [ ] . this aspect might be of immediate understanding, however, it also implies to recognize why acute peaks of glycemia, episodes of hypoglycemia or, even worse, the exposure of the patients to huge glucose variability during the stay in icu are all rather deleterious. acute hyperglycemia produces oxidative stress followed by an enormous production of inflammatory cytokines [ ] , a situation that obviously must be avoided during any stay in icu, but particularly during the stay for covid- . it is well known that during this disease a massive cytokines storm can occur, with severely damaging effects [ ] . hypoglycemia can produce the same effects as acute hyperglycemia and can expose directly people to the risk of dying [ , ] . furthermore, how hypoglycemia is recovered might be dangerous: hyperglycemia post-hypoglycemia is also an issue, leading to an enhancement of inflammation [ ] . finally, there are plenty of reports in the literature that glucose variability is producing a worsening of the prognosis in icu [ , [ ] [ ] [ ] [ ] even when glucose is kept in normal range [ ] . so it seems advisable that glucose variability should be avoided. glucose variability also induces the generation of the oxidative stress and the release of inflammatory cytokines [ ] . is the issue of glycemic control also of importance for people with diabetes and covid- ? it seems, unfortunately, the case, according to reports on how glycemia was managed in several situations during this pandemic [ , ] . when facing high glucose levels due to severe infection per se, it is often required that patients are switched to insulin, with some concerns that insulin treatment might not always be safely managed in such situations, unless insulin is administered intravenously via an exactly dosing perfusion device to avoid subcutaneous absorption irregularities in critically ill patients [ , ] . hyperglycemia is common in the intensive care unit (icu) both in patients with and without a previous diagnosis of diabetes [ ] . the optimal glucose range in the icu population is still a matter of debate. given the risk of hypoglycemia associated with intensive insulin therapy, current recommendations include treating hyperglycemia after two consecutive glucose > mg/ dl with target levels of - mg/dl for most patients [ ] . the optimal method of sampling glucose and delivery of insulin in critically ill patients remains elusive. while point of care glucose meters are not consistently accurate and have to be used with caution, continuous glucose monitoring (cgm) is not standard of care and is not yet generally recommended for inpatient use. the advent of new technologies, such as electronic glucose management, cgm, and closed-loop systems, promises to improve inpatient glycemic control in the critically ill with lower rates of hypoglycemia [ ] . the issue of optimal glycemic control is certainly even more complicated during the management of covid- because high doses of glucocorticoids are often used [ ] . glucocorticoids improve the prognosis of covid- but, of course, induce or worsen hyperglycemia [ ] . in the case keeping normal glycemia may be very challenging [ ] . another challenge in managing glycemia during the stay in icu, particularly during the early phase, is the background anti-hyperglycemia therapy. while for several therapies, such as dipeptidyl-peptidase inhibitors (dpp inhibitors), sodium-glucose-transporter- inhibitors (sglt- inhibitors), pioglitazone, alpha-glucosidase inhibitors, metformin and short-acting glucagon-like-peptide- receptor agonists (glp- ra) (exenatide and lixisenatide) their action is only shortly enduring after they are stopped, this cannot be the case for long-acting insulins but particularly for the long-acting glp- ra (dulaglutide, exenatide la, liraglutide and semaglutide) [ ] . their action will add to that of insulin used during the treatment in icu and must be considered in choosing the insulin dose. on the other hand, many of them show an anti-inflammatory activity, which could be quite helpful during covid- [ ] (fig. ) . another rising problem might be the concomitant use of hydroxychloroquine that, even it is controversial [ ] , sometimes is used for preventing the effect of the "severe acute respiratory syndrome coronavirus " (sars-cov- ) [ ] . hydroxychloroquine has a proven hypoglycemic effect, therefore also in this case the insulin treatment must be very carefully managed in order to avoid episodes of hypoglycemia [ ] . intriguingly, there is also evidence that optimal covid- infection management with tocilizumab is not achieved during hyperglycemia in both diabetic and non-diabetic patients [ ] . increased attention is needed regarding the proper hydration of the diabetic patient with covid- in the icu [ ] . hyperhydration can induce the onset of life-threatening pulmonary oedema due to the severity of lung damage during corona infection. serum k levels are equally important, with a major risk of hypokalaemia, frequently associated with covid- , possibly due to hyperaldosteronism caused by elevated angiotensin [ ] . insulin treatment may worsen hypokalaemia if not corrected in time [ ] . diabetes is very often accompanied by hypertension [ ] . fortunately, the issue of the possible role of angiotensin-converting-enzyme inhibitors and angiotensin-receptor-blockers in favoring the penetration of the sars-cov- , due to the increasing receptor for the virus "angiotensin-converting-enzyme- " (ace ), seems to be over [ ] . new specific data coming from people with the covid- , are certainly reassuring on this point [ , ] . in the coronado study, which included patients with diabetes, neither hypertension nor treatment by renin-angiotensin-aldosterone system blockers were associated with a worse prognosis [ ] . anyhow, the control of blood pressure remains an important point in the management of people in icu and of course this particularly applies to people with diabetes. fig. possible issues in the management of people with diabetes and covid- in icu. several issues are present during the management of people with diabetes and covid- in icu. tight glycemic control, avoiding hypoglycemia and glucose variability improves the prognosis. this goal, to be achieved, needs insulin infusion and continuous glucose monitoring (cgm). *moreover, the achievement of tight glucose control may be influenced by the background anti-hyperglycemic therapy and by the concomitant therapy with hydroxychloroquine (risk of hypoglycemia) or corticosteroids (inducing hyperglycemia). **the evaluation of the meaning of several biomarkers related to the risk of cardiovascular complications, thrombosis and inflammation must be careful, because many of them are already altered by diabetes itself. there is no contraindication, however, to the use of acei or arbs to control blood pressure. acei angiotensin-converting-enzyme inhibitors, arbs angiotensin-receptor-blockers, cv cardio-vascular, cgm continuous glucose monitoring, crp c-reactive protein, hs-troponin high-sensitive troponin, icu intensive care unit, il- interleukin- , nt-probnp n-terminal-pro-brain natriuretic-peptide several biomarkers have been suggested to be helpful in stratification of the risk during the covid- . their value as helpful tools in the case of covid- in people with diabetes needs a careful evaluation. covid- can cause serious acute cardiovascular events [ ] . moreover, people with a previous cardiovascular disease are more prone to a worse prognosis if affected by sars-cov- [ ] [ ] [ ] [ ] [ ] . a pre-existing cardiovascular disease very often accompanies diabetes, therefore, people with diabetes also for this reason may be exposed to a more serious complication when having the covid- . furthermore, a large proportion of people with diabetes has asymptomatic coronary artery disease [ , ] which can increase the risk of acute coronary syndrome, heart failure and arrhythmia during the covid- due to proinflammatory process, hypercoagulability and sympathetic stimulation. qt interval is also often increased in people with diabetes, as a consequence of cardiac autonomic neuropathy [ , ] . qt interval may be further lengthened by hypoglycemia and by drugs used during the covid- and by hypokalemia and needs to be carefully monitored. hs-troponin has been suggested for monitoring the risk of myocardial infarction during the covid- [ , ] . however, in the case of diabetes, increased levels of hs-troponin have been reported [ ] , as signal of an existing chronic heart damage, therefore its use for monitoring heart risk in diabetes during covid- deserves some caution. the situation is not different for heart failure, which again, has been described as a serious complication of covid- [ , ] . the measurement of the "n-terminal-pro-brain natriuretic-peptide" (nt-probnp) to define the risk for heart failure in covid- has been suggested [ ] [ ] [ ] . however, plasma nt-probnp level in a patient with covid- must be seen as a marker of both the presence and extent of pre-existing cardiac disease and the acute haemodynamic stress related to covid- . as for hs-troponin, increased levels of nt-probnp have been often reported in diabetes [ , ] . according to various studies, an asymptomatic heart failure can be present in up to more than % of people with diabetes [ ] [ ] [ ] . this condition is characterized by an increase of plasma nt-probnp. so, again, the usefulness of a marker, in this case the nt-probnp, needs a careful evaluation in the presence of diabetes and covid- . thrombosis has been found to occur very often during the covid- and it is one of the most serious complications [ ] . the measurement of d-dimer is very useful in the prediction of the risk for a thrombotic event and its evaluation has been suggested regarding the management of covid- patients [ , ] . the situation in diabetes looks more complicated. d-dimer is often elevated in diabetes [ , ] . it is just the index of increased thrombophilia, which is highly prevalent in diabetes [ ] . the thrombophilia in diabetes is related to an imbalance between thrombosis and fibrinolysis [ ] . this status suggests in one side that the evaluation of the thrombotic status in diabetes during the admission in icu using the d-dimer should be very careful, but at the same time that an anticoagulation could be very helpful. in this context the role of hyperglycemia also deserves attention. an acute increase of glycemia may activate thrombin formation [ ] , convincingly through the glycation of the antithrombin iii, a phenomenon that can be reversed by a fast control of hyperglycemia or by heparin [ ] . heparin administration is largely suggested in the case of covid- , so it seems true that there is further reason for its use in the presence of diabetes [ ] . finally, it has been recently reported that glucose variability may increase the platelet reactivity [ ] . therefore, regarding the risk of thrombosis, there are good reasons to keep glycemia under a strict control, in association with anticoagulation. markers of inflammation, particularly c-reactive-protein and interleukin- have also been suggested as tools for monitoring the severity of the covid- [ , ] . again diabetes has a particular situation. low-grade inflammation is present in this disease [ ] , therefore, as for thrombosis and heart failure, the significance of altered values of these markers needs a careful evaluation in people with diabetes and covid- . furthermore, as reported above, an acute increase of glycemia as well as glucose variability are accompanied by an increased production of cytokines [ , ] , an effect that must be avoided in the covid- . most of diabetic patients are routinely on lipid-lowering treatment, in particular on statins in accordance with the current diabetes and cardiovascular disease guidelines [ ] . statins have well-known anti-inflammatory effects and improve endothelial function, which may be protective against cardiovascular complications during covid- . however, through various mechanisms statins may enhance compensatory immune signals [ ] . in addition, similar to renin-angiotensin-aldosterone system blockers, experimental studies showed that statins also augment the ace receptor expression [ ] and might thus facilitate the penetration of sars-cov- into the cells. whether statins may be beneficial or harmful during virus-induced acute respiratory distress syndrome is controversial [ , ] . further investigations are urgently required to clarify the interplay of these complex mechanisms with the new coronaviruses. in addition statins may cause myotoxicity. a markedly increase in creatine kinase may be observed in some patients with covid- [ ] . the benefit of statins in cardiovascular prevention is well established in people with diabetes. in this context there is no evidence for withdrawing statins during covid- . however creatin kinase should be carefully monitored and, if increased, statin therapy should be temporarily withheld in order to avoid rhabdomyolysis. probably it is not well recognized that all we have reported above, which is true for type diabetes, applies also and particularly and more seriously to type diabetes [ , ] . type diabetes has the same, albeit not more than type diabetes, risk for cardiovascular events [ ] . moreover, it is important to note that many old people may have today type diabetes. data are reassuring, showing that people with type diabetes are not more exposed to sars-cov- infection [ ] nor to more severe outcomes compared to patients with type diabetes [ ] . however, type diabetes is more complicated to manage and probably deserves a special attention when admitted to icu for covid- . managing people with diabetes in any acute setting is always very difficult. covid- has a very severe prognosis for people with diabetes and evidence shows that a tight glucose control could be very helpful. in the case of covid- people with diabetes are more exposed to 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key: cord- -ccg nmf authors: bonora, benedetta maria; boscari, federico; avogaro, angelo; bruttomesso, daniela; fadini, gian paolo title: glycaemic control among people with type diabetes during lockdown for the sars-cov- outbreak in italy date: - - journal: diabetes ther doi: . /s - - - sha: doc_id: cord_uid: ccg nmf introduction: in late february , due to the spread of severe acute respiratory syndrome coronavirus- (sars-cov- ), the italian government closed down all educational and sport activities. in march, it introduced further measures to stop the spread of coronavirus disease (covid- ), placing the country in a state of almost complete lockdown. we report the impact of these restrictions on glucose control among people with type diabetes (t d). methods: data were collected on individuals with t d who were monitoring their glucose levels using a flash glucose monitoring device and remotely connected to the diabetes clinic on a cloud platform. we retrieved information on average glucose, standard deviation and percentage time in hypoglycaemia (< mg/dl), glucose range ( – mg/dl) and hyperglycaemia (> mg/dl). we compared glycaemic measures collected during lockdown to those collected before the sars-cov- epidemic and to the periods immediately before lockdown. results: in patients who had stopped working and were at home as a result of the lockdown, overall glycaemic control improved during the first days of the lockdown as compared to the weeks before the spread of sars-cov- . average glucose declined from ± mg/dl (week before lockdown) to ± mg/dl (lockdown; p = . ) and the standard deviation improved significantly. time in range increased from . to . % (p = . ), and time in hyperglycaemia decreased from . to . % (p = . ). the number of scans per day remained unchanged. in patients who continued working, none of the measures of glycaemic control changed during lockdown. conclusion: despite the limited possibility to exercise and the incumbent psychologic stress, glycaemic control improved in patients with t d who stopped working during the lockdown, suggesting that slowing down routine daily activities can have beneficial effects on t d management, at least in the short term. why carry out this study? in march , italy was placed under lockdown due to the outbreak of the new coronavirus disease. diabetes management during lockdown was particularly challenging. using data collected by remote monitoring of glucose sensors, we investigated whether glycaemic control in people with type diabetes (t d) during lockdown improved or worsened. what was learned from the study? individuals with t d who stopped working during lockdown significantly improved their glucose control while those who continued working (essential services) showed no change in glucose control. these results suggest that slowing down routine daily activities can achieve beneficial effects on the short-term management of t d. the long-term effects of lockdown and the factors that affect glucose control in this particular situation deserve future investigation. achieving glycaemic control is a complex task for people with type diabetes (t d) as it involves multiple domains of daily functioning [ , ] . to maintain glucose levels that are as much as possible within range, patients need to pay attention to meals, insulin doses, exercise regimens, working activities, social relations and psychological stress, as well as exercise selfcontrol [ ] . this continuous challenge results in people with t d occasionally deprioritizing glycaemic control in favour of other activities [ ] . glucose control may improve during holidays, but this improvement is highly variable [ ] [ ] [ ] . in december , a new coronavirus (cov) strain that causes severe acute respiratory syndrome emerged in wuhan (china), ultimately referred to as severe acute respiratory syndrome coronavirus (sars-cov- ), and rapidly spread throughout the world [ ] . in february and march , italy was the second most affected country worldwide [ ] . to reduce the spread of infection, in late february , the italian government issued a series of restrictions that, in march , culminated in an almost complete lockdown of the country [ ] . this lockdown intially involved all sport and educational activities but was then extended to commercial activities and most non-essential services. during lockdown, all citizens were requested to ''stay at home'' [ ] . outpatient clinics were closed while hospitals were coping with thousands of patients infected with sars-cov- . the sars-cov- pandemic not only caused morbidity and mortality among people with cov disease but also imposed a heavy burden on societal and population health [ ] . it is expected that individuals with chronic disease, such as diabetes, will suffer the most from the prolonged lockdown due to limitations in access to outpatient clinics and services. remote glycaemic monitoring through cloud platforms has enabled diabetes specialists to interact with individuals with t d during the sars-cov- pandemic lockdown. the widespread use of the flash glucose monitoring system (fgm) among patients with t d [ ] has allowed healthcare professionals (hcps) to monitor these patients through a web-based interface that records real-time sensor readings. of note, telemedicine has been shown to improve psychosocial outcomes in young adults with diabetes [ ] . according to a recent metaanalysis, fgm has the potential to improve overall glucose control [ ] and to reduce hypoglycaemia in individuals with t d [ , ] . in this study, we examined glycaemic control during the first week of lockdown against the spread of sars-cov- in people with t d using fgm in italy in comparison to the prelockdown period. the study was approved by the ethical committee of the university hospital of padova. all procedures were performed in accordance with the helsinki declaration of , and its later amendments, and was in agreement with national regulations. the study was conceived as a retrospective data collection, and all patients provided written informed consent to the reuse of clinical data for research purposes. patients with t d who were eligible for inclusion in the study met the following criteria: attended the diabetes outpatient clinic of the university hospital of padova; lived in the area; were using the freestyle libre fgm system (abbott diabetes care, rome, italy) for at least months; were sharing sensor data with the diabetes outpatient clinic on a web-based cloud system (libreview; abbott diabetes care); and had [ % coverage of sensor data. the libre-view platform is intended to assist both people with diabetes and hcps in reviewing, analysing and evaluating sensor data to support diabetes management. in order to record only spontaneous changes in glycaemic control, patients who had already sought therapeutic advice were excluded from enrolment. patients had provided online informed consent to be remotely connected to the diabetes clinic. diagnosis of t d was based on the american diabetes association (ada) criteria and was confirmed by positive autoantibody testing [ ] . for all patients, we retrieved the following data: age, sex, diabetes duration, body mass index, history of hypertension and smoking habit, most recent glycated haemoglobin (hba c) values, lipid profile, urinary albumin excretion rate (uaer), estimated glomerular filtration rate (egfr; ckd-epi equation [ ] ). the presence of chronic complications was recorded as follows. nephropathy was defined as a uaer [ mg/g or egfr \ ml/min/ . m . somatic neuropathy was defined based on an assessment using the michigan neuropathy screening instrument, and eventually confirmed by nerve conduction velocity testing. autonomic neuropathy was defined based on the results of cardiac autonomic tests performed with the neurotester instrument (meteda srl, san benedetto del tronto, italy), including lying-to-standing response, valsalva manoeuvre, deep breathing and orthostatic hypotension. retinopathy (any stage) was defined based on the analysis of digital retinography, as scored by expert ophthalmologists. coronary artery disease was defined as a history of myocardial infarction or coronary revascularization, or evidence of myocardial ischemia upon stress test (when available). peripheral arterial disease was defined as a history of claudication or rest pain, peripheral artery revascularization or an ankle-brachial index of \ . . cerebrovascular disease was defined as a history of stroke or transient ischemic attack or carotid atherosclerosis (symptomatic or asymptomatic). we also collected information on concomitant medications, other than insulin, including metformin, sodium glucose cotransporter- inhibitors and drugs for the management of concomitant risk factors. raw data on sensor glucose readings were retrospectively retrieved from all patients at -min intervals. to avoid an impact of scan frequency on average glucose levels, we did not consider glucose readings from sensor scans in our analysis. raw data were imported on a dedicated spreadsheet, and the following metrics were computed: average glucose with standard deviation (sd); coefficient of variation (cv%; expressed as the percentage of average glucose); time in hypoglycaemia (\ mg/dl); time in glucose range ( - mg/dl); time in hyperglycaemia ([ mg/dl); and number of scans per day. as per convention, we set a cutoff of mg/dl to define high/low average glucose and a sd cutoff of mg/dl to define stable/ unstable control. the primary endpoint was average glucose. these variables were calculated for each of the following periods ( fig. a ): months before the sars-cov- outbreak in italy; week before the sars-cov- outbreak in italy; from the closure of sport and educational activities to lockdown of the padova area, when commercial activities and non-essential services were closed (period ); and the first week after lockdown (period ). patients were divided into groups based on whether they stopped their working activities during lockdown or whether they continued working during lockdown because of being involved in essential services (e.g. workers in the healthcare system or food supply chain). patients who continued working served as negative controls for those who stopped working during the lockdown period. continuous variables are presented as the mean ± sd if normally distributed or as the median a total of patients with t d were enrolled in the study, then categorized into one of two groups based on whether they stopped working (n = ) or continued working (n = ) during the lockdown. clinical characteristics of the two groups are reported in table . none of the patients were known to be (have been) infected with sars-cov- nor to be (have been) quarantined for close contact with infected people. the patients who stopped working due to the lockdown had an average age of . years, % were male and average diabetes duration was years. the mean latest available hba c value was . %, and the prevalence of complications was low. when data collected during the week before the sars-cov- outbreak in italy were compared to those of the first week of lockdown (period ), average glucose had decreased from . ± . mg/dl ( . ± . mmol/l) to . ± . mg/dl ( . ± . mmol/l; p = . ; fig. b) , which is equal to a reduction of . ± . mg/dl ( . ± . mmol/l). the standard deviation of sensor readings decreased from . ± . mg/ dl ( . ± . mmol/l) to . ± . mg/dl ( . ± . mmol/l; p = . ). as a result of the simultaneous improvement in average glucose and the standard deviation, patients moved from a high-unstable profile towards a lowstable profile (fig. c) . the number of patients in the low-stable profile area increased from three to eight (p = . ). however, the cv%, which is a better measure of glycaemic stability according to international consensus and recommendations [ , ] , did not change substantially across the periods considered. time in hypoglycaemia was not significantly changed, whereas time in range increased (from . ± . to . ± . %; p = . ) and time in hyperglycaemia decreased (from . ± . to . ± . %; p = . ; fig. d ). the number of scans per day did not change significantly (from . ± . to . ± . ; p = . ). reduction of average glucose was directly correlated with baseline average glucose (r = . ; p = . ), but not with the number of scans per day. when data collected during period were compared to those collected during the months before sars-cov- spread, the same significant improvements were noted ( table ) . data collected during period were not significantly different from those collected week or months before sars-cov- outbreak. data are expressed as mean ± standard deviation or as the number (of patients) with the percentage in parenthesis. the urinary albumin creatinine ratio is expressed as the median with the interquartile range in square brackets *significant different between patient groups at p \ . hdl high-density lipoprotein, ldl low-density lipoprotein, mdi multidose insulin, csii continuous subcutaneous insulin infusion, sglt- i sodium glucose cotransporter- inhibitor, acei angiotensin converting enzyme inhibitor, arb angiotensin receptor blockers period : from the closure of sport and educational activities to lockdown of the padova area, when commercial activities and non-essential services were closed; period : the first week after lockdown patients who continued working during the lockdown (n = ) had an average age of years, . % were male and average diabetes duration was . years (and thus longer than that of the group not working). eight patients were on insulin pump therapy. none of the patients who continued to work showed improvement in any of the measures of glucose control during the lockdown period (period ) compared to the months or the week before the sars-cov- outbreak: average glucose, standard deviation, cv%, time in hypoglycaemia, time in range and time in hyperglycaemia remained unchanged (table ) , as did the number of scans per day. no difference was observed regarding any change in glucose control metrics among those who were on the insulin pump and those who were on a regimen of multiple daily insulin injections. our data show that, during the first week of lockdown due to the sars-cov- outbreak in north-east italy, patients with t d who stayed at home achieved a significant improvement in glucose control. among patients with t d followed at the same clinic who continued working in the same period, many of whom were on insulin pump therapy, no deterioration of glucose control was observed. the sars-cov- pandemic represents a huge challenge to public health worldwide [ ] , and healthcare services have faced severe challenges during outbreaks of the coronavirus disease (covid- ), resulting in major cut backs in the care provided to people with chronic diseases, including diabetes [ , ] . many outpatient clinics have had to change their routine interactions with patient and use telemedicine to monitor patients at home [ ] . in italy, the widespread use of fgm among people with t d allowed these patients to be remotely connected to the clinic through the cloud. diabetes professionals were concerned that glucose control could worsen during lockdown because of the limited possibility to exercise and the severe psychologic stress imposed by social distancing in a cultural environment heavily reliant on direct inter-personal relationships. during the outbreak, most non-essential activities were shut down, and most citizens stopped their usual working routine or turned to working at home. however, some people, such as those involved in healthcare or the food supply chain, continued to work during the lockdown. our observation that glucose control improved during the first week of lockdown in people with t d who stayed at home is reassuring and suggests that a slowing down of routine activities can have favourable effects on glucose control in the short term. remarkably, the reduction in average glucose and the increase in time in range were not paralleled by an increased time in hypoglycaemia, which remained stable. we speculate that such an improvement occurred because patients had more time to concentrate on diabetes control and had a more regular lifestyle, including the timing and composition of meals, while not being exposed to workplace stress [ ] . in addition, the knowledge that diabetes worsens the outcomes of covid- [ , ] may have improved patients' awareness and compliance to diabetes management. to evaluate whether glucose control changed in all patients with t d during lockdown, irrespectively of whether they stayed at home or not, we included a group of patients who continued working. the observation that glucose control did not improve in this subgroup of t d patients supports our interpretation. however, the groups of patients who stopped working and those who continued their usual working activities were not comparable because the latter had a better baseline glucose control than those who stayed at home, and [ % were on insulin pump therapy. users of pump therapy represent approximately % of patients with t d at our clinic, and % of t d patients nationwide [ ] . the frequent use of insulin pump therapy among this group of patients is probably related to the fact that most were healthcare workers and/or shift workers who often need pump therapy to cope with their lifestyle and working schedules. patients who continued working had a higher time in range at baseline, such that further improvements were more difficult to obtain. yet, it is reasonable to assume that these individuals were subjected to stronger challenges during lockdown, including exercise limitations, social distancing, workplace stress, and fear of infection. therefore, that these patients maintained good glycaemic control is reassuring in terms of their effective self-management of diabetes. we speculate that the use of fgm combined with insulin pump therapy contributed to this effect [ ] ; for example by limiting diabetes-related distress [ ] . we acknowledge that detailed information to interpret the drivers of glucose control during lockdown, such as changes in insulin doses, consumption of snacks and exercise, were not available and should be investigated in future studies. in addition, we included patients with t d having relatively good glycaemic control and showing frequent sensor use. therefore, it remains unclear whether the same results would apply to patients with worse glucose glycaemic control or less frequent sensor scans. finally, we did not analyse glycaemic control in the subsequent weeks of lockdown because most patients were remotely contacted by the physicians from the clinic with advice on how to manage diabetes, thereby introducing bias. hence, the medium-and long-term impact of lockdown on glucose control remains unknown. in summary, we report that glucose control improved in people with t d who stayed at home during the first week of lockdown due to covid- . this observation suggests that slowing down routine activities can have beneficial effects on t d control in the short term. however, the long-term effects of lockdown and the factors that affect glucose control in this particular situation deserve future investigation. boscari, daniela bruttomesso and gian paolo fadini have received lecture fees or other support from abbott, the manufacturer of the flash glucose monitoring system and cloud platform described in this study. benedetta maria bonora and angelo avogaro declare no conflict of interest in connection with the submitted material. compliance with ethics guidelines. the study was approved by the ethical committee of the university hospital of padova. all procedures were performed in accordance with with the helsinki declaration of , and its later amendments, and was in agreement with national regulations. the study was conceived as a retrospective data collection, and all patients provided written informed consent to the reuse of clinical data for research purposes. data availability. the datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. open access. this article is licensed under a creative commons attribution-noncommercial . international license, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/bync/ . /. diabetes resilience: a model of risk and protection in type diabetes the relationship between diabetes self-management and metabolic control in youth with type diabetes: an integrative review health-related quality of life and glycaemic control among adults with type and type diabetes-a nationwide cross-sectional study diabetes distress, intentional hyperglycemia at work, and glycemic control among workers with type diabetes profiling intra-patient type i diabetes behaviors observational study of diabetes management in type diabetic school-age children during holiday versus school days seasonality of type diabetes mellitus in children and its modification by weekends and holidays: retrospective observational study a novel coronavirus from patients with pneumonia 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with type diabetes effectiveness of the freestyle libre flash glucose monitoring system on diabetes distress among individuals with type diabetes: a prospective study funding. no funding or sponsorship was received for this study or publication of this article.authorship. all named authors meet the international committee of medical journal editors (icmje) criteriafor authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.authorship contributions. benedetta maria bonora and federico boscari contributed equally. key: cord- - u i qmc authors: almomani, huda y.; pascual, carlos rodriguez; al-azzam, sayer i.; ahmadi, keivan title: randomised controlled trial of pharmacist-led patient counselling in controlling hypoglycaemic attacks in older adults with type diabetes mellitus (rose-adam): a study protocol date: - - journal: res social adm pharm doi: . /j.sapharm. . . sha: doc_id: cord_uid: u i qmc introduction: hypoglycaemia is one of the most serious adverse effects of diabetes treatment. older adults are at the highest risk to develop hypoglycaemia. several studies have established the important positive role of educational interventions on achieving glycaemic control and other clinical outcomes, however, there is still a lack in studies that evaluate the impact of such type of interventions on hypoglycaemia risk in elderly patients with type diabetes. the purpose of this research is to evaluate the effectiveness of pharmacist-led patient counselling on reducing hypoglycaemic attacks in older adults with type diabetes mellitus. methods: and analysis: this study is an open-label, parallel controlled randomised trial, which will be conducted in the outpatient clinics at the largest referral hospital in the north of jordan. participants who are elderly (age ≥ years), diagnosed with type diabetes mellitus, and taking insulin, sulfonylurea, or any three anti-diabetic medications will be randomly assigned to intervention (sugar handshake) and control (usual care) groups. the sugar handshake participants will have an interactive, individualised, medications-focused counselling session reinforced with a pictogram and a phone call at week six of enrolment. the primary outcome measure is the frequency of total hypoglycaemic events within weeks of follow up. secondary outcomes include the frequency of asymptomatic, symptomatic, and severe hypoglycaemic events, hypoglycaemia incidence, and time to the first hypoglycaemic attack. we will also conduct a nested qualitative study for process evaluation. ethics and dissemination: the human research ethics committee of the university of lincoln and the institutional review board of king abdullah university hospital approved this protocol. the findings of this study will be presented in international conferences and published in a peer-reviewed journal. trial registration number: the study protocol has been registered with clinicaltrials.gov, nct . background hypoglycaemia is the major limiting factor in diabetes management. hypoglycaemia has been found to be associated with cardiovascular events such as myocardial infarction, arrhythmias and cardiovascular mortality as well as cerebral complications such as dementia. - . additionally, hypoglycaemia can impact patients' quality of life. patients with moderate or worse symptoms of hypoglycaemia are less satisfied with their treatment and report poorer adherence to their medications. the great burden of hypoglycaemia is largely presented by the considerable health care cost resulting from hospitalisations, ambulance services, emergency department visits, and absenteeism from work. , older adults are the most susceptible age group to develop hypoglycaemia and to experience hypoglycaemia-related complications. the correlation between ageing and hypoglycaemia in type ii diabetes is multifactorial. [ ] [ ] [ ] [ ] [ ] factors such as physiological changes in elderly that would affect the pharmacokinetics profile of anti-diabetic drugs, comorbidities that affect heart and kidneys, nutrition changes and cognitive impairment that could affect concordance and compliance with treatment regimen [ ] [ ] [ ] [ ] [ ] . as the population of older adults is increasing, globally; it is expected to see an increase in the prevalence of t dm in older adults. , in jordan, the prevalence of diabetes in people aged years and over increased significantly over ten years period. it is estimated that the number of elderly persons in jordan will be three times higher in than it was in , consequently more older adults will be at risk of developing type ii diabetes and diabetes-related complications. there are several studies on the association between hypoglycaemia and patient characteristics such as patients' perspectives and attitudes towards diabetes management skills, self-monitoring of blood glucose, and non-adherence to anti-diabetic medications in jordanian population. - however, there is a dearth of data on the interventions that could potentially prevent hypoglycaemia in such patients, especially the older population. therefore, it is imperative to develop diabetes-related care strategies targeted to this broad population of patients to cope with the growing figures in the future. in the context of diabetes, pharmacist-led care interventions appear to have a pivotal role in glycaemic control, improving self-care activities, medication adherence, improving quality of life, and reducing related complications. - pharmacist-led care interventions can be individualised to each patient to achieve glycaemic control. , , however, a few randomised controlled trials (rcts) have investigated the impact of such interventions on hypoglycaemia in adults diagnosed with t dm. although elderly people are considered heterogenous group with different characteristics from younger adults, none of these trials has explored the effect of educational interventions in this age category. jordanian pharmacy education equips the pharmacists with robust clinical knowledge and clinical skills to work with other healthcare professionals to provide optimal quality care to the patients . therefore, the aim of this study is to evaluate the effectiveness of pharmacist-led patient counselling on preventing hypoglycaemia in older adults with t dm. educational interventions are considered to be "complex" interventions compared with classic examples of drug interventions in rcts. that is an educational interventions' success or failure could be attributed to a myriad of factors besides the interventions' effectiveness. the factors such as the delivery of the intervention, understanding of the intervention by the patients and implementation of intervention would decide the fate of an educational intervention. for this reason, a process evaluation is valuable to identify whether an intervention works and how, barriers for its implementation, and how to improve it in the future. undertaking qualitative studies to evaluate the interventions during the implementation stage helps in modifying the ongoing interventions as well as the study design to make them more feasible and effective. the study will be a single-centre, two groups, : parallel, open-label, pragmatic randomised controlled trial with a nested process evaluation embedded; and will be conducted in two clinics at a referral tertiary hospital in jordan. participants will be randomly assigned to either the intervention group hereinafter referred to as the "sugar handshake" group or the control group. figure illustrates the detailed study flow chart. hypoglycaemic episodes pose some challenges as the frequency of hypoglycaemic events is the primary factor in calculating the sample size. , we referred to the most relevant study that used a similar outcome measure, methodology and intervention to our research to calculate the needed sample size. the previous study found that the mean total number of hypoglycaemic attacks in the control and the intervention groups were . ± . and . ± . per patient in weeks, respectively. we used the reported frequency of hypoglycaemic attacks in both groups to calculate the minimum required sample size. therefore, we need to recruit at least patients to achieve a significance level of . and a study power of %. accounting for % to compensate attrition rate and missing data, the final sample size wished to be recruited is participants ( in each group). we will recruit older adults who are years and above, diagnosed with t dm and being prescribed sulfonylurea, insulin, or any three anti-diabetic medications. exclusion criteria include patients unable to understand instructions or to give consent, diagnosed with haemolytic anaemia or haemoglobinopathies, on palliative care for cancer, with advanced- stage or end-stage diseases who are terminally ill, diagnosed with psychosis or severe depression, or with life expectancy < months, impaired mental capacity, unwilling to take home glucose measurements or to use the glucose meter, or unwilling to return for follow up. patients who have a partner or a first-degree relative who has been enrolled in the study, are excluded as well. we will use two recruitment methods to reach potentially eligible patients: an advertisement placed in the reception room where patients wait for their appointments, and through direct identification of potentially eligible patients at the recruitment sites. ha will be responsible for recruiting participants in the endocrinology and diabetic foot care clinics meanwhile the research assistant (ra) will recruit from the cardiology clinics. ha and the ra will explain the trial purpose and processes and provide participant information sheets (supplementary file ) to the interested patients. they will also confirm the eligibility of patients who are willing to participate and will ask them to sign a written consent form we will randomly assign participants to the intervention and control groups on a : basis. the random sequence will be generated using the website (www.randomization.com) to generate the randomisation schedule. envelopes will be used to conceal the allocation and will be opened by the researcher sequentially at the time of each participant's enrolment. the study envelopes will contain the study name, the participants' codes, the group to which the participants are randomised. the randomisation sequence and the study envelopes will be prepared by a third independent party who will not be involved in the study. the envelopes will be closed and opaque and will be given to the researcher and the ra who are involved in conducting the study. the envelopes that will contain the group allocation will be kept in a locked cabinet in the hospital. blinding since this is an open-label study, the patients and the data collectors will not be blinded to the assigned group. eligible patients will be informed about the purpose of the study and the study-related activities before they sign the consent form. proper measures will be taken along the trial duration to minimise performance and ascertainment bias that may result from unblinding participants. all participants will be unblinded to the study groups and to the real purpose of the trial at the follow-up visit that would mark the end of the trial. additionally, participants who are assigned to the control group will receive the sugar handshake intervention at the follow- up visit. intervention group (sugar handshake) the educational intervention, the sugar handshake, is designed to promote behavioural change to prevent hypoglycaemia. we applied the principles of the behaviour wheel theory (bcw)to design the intervention. our educational intervention would enhance the physical and psychological capabilities of the patients through improving their knowledge and skills in managing and preventing hypoglycaemia. the intervention would also lead to the behavioural change by a conducive environment to promote behaviour change by addressing the physical and cultural needs of the patients. we have structured the reporting of the intervention in line with the tidier (template for intervention description and replication) checklist and guide. participants assigned to the sugar handshake group will receive individualised counselling regarding hypoglycaemia in addition to the usual care provided at the trial sites. the intervention is designed by ha who is a pharmacist with prior work experience in patient counselling and pharmacist-related clinical services. ha has trained the ra on delivering the intervention. the intervention is delivered in two steps i.e., a face-to-face conversation at the enrolment visit followed by a phone call six weeks later. step one: face-to-face conversation at the enrolment visit the sugar handshake intervention will cover comprehensive strategies to prevent and handle hypoglycaemia with instructions related to anti-diabetic medications and managing drug-related problems. table step two: phone call at the th week: participants will receive a -minute follow up call at week six of enrolment; so that the first step of the intervention would be reinforced as well as participants' queries/questions would be answered. participants will also be asked about the number and timing of having hypoglycaemic attacks during the first six weeks in the trial to re-consider modifying the intervention components. participants in this group will be offered guidance on hypoglycaemia diagnosis and the proper use of the glucose meters in addition to the usual care. they will also be provided with instructions on hypoglycaemia treatment. as participants in both groups will receive the same information regarding hypoglycaemia recognition, they will have similar ability to recognise hypoglycaemic attacks. at week of enrolment, participants will receive a phone call to remind them of using the glucose meters and documenting hypoglycaemic attacks. of special note, participants who complete the trial duration will receive the intervention at the debrief visit and after returning the hypoglycaemia diaries. all participants in both groups will be given glucose meters and test strips with a demonstration on proper use to measure their blood glucose levels at morning before breakfast daily for consecutive weeks. they will also be handed diaries and instructed to additionally, it is impractical for dm patients to measure their bg levels frequently to diagnose hypoglycaemia. hence, it is imperative to account for both symptomatic and asymptomatic types of hypoglycaemia. we will use diaries to measure types of hypoglycaemia and we will ask participants to fill in the diary on a daily basis for weeks. participants will be asked to fill in the diary with the date of each day and the fasting blood glucose reading. additionally, they will be asked to tick on the boxes for every time they experience severe hypoglycaemia, symptoms of hypoglycaemia at the time of fasting blood glucose measurement, and symptoms of hypoglycaemia during the rest of the day. participants will document a symptomatic attack if the symptoms resolve after receiving the corrective actions. the rate of each type of hypoglycaemia will be measured according to the hypoglycaemia diaries filled by the participants. severe hypoglycaemia will be measured directly according worked and what didn't, and how the study could be improved in future research. we will collect qualitative data using semi-structured interviews from a handful of participants in each study group. we have prepared the interview guide (table ) based on the objectives of the study and the mrc domains for process evaluation. table : interview schedule you have previously read in the participant information sheet that we are conducting a phone interview as a part of this study and you accepted to participate in it. therefore, i would like to ask you some questions about your experience with the study processes that have been provided to you at the inclusion visit. the information will help us in improving several aspects of the study. the interview should take about minutes. are you available to respond to the questions at this time? . i would like to start by asking: how do you describe your participation in the study so far? if needed, the interviewers may explain the question by the follow-up question: how do you rate your participation in the study from good to poor and why? . what has worked for you from the study processes that you were asked to do? -why do you think they have? what hasn't worked for you from the study processes that you were asked to do? -why do you think they haven't? . from your perspective, how the study could be improved? please consider any aspects of the study that you think could be improved. per-protocol analysis will be conducted including participants who are compliant to % or more of the study protocol. , the missingness in the primary outcome will be handled under the assumption of "missing at random" rather than "missing completely at random", because we are expecting that the probability of missing data depends on observed covariates or outcomes rather than unobserved data. therefore, the method chosen to handle missing data in the outcomes is multiple imputations. , descriptive analysis will be used across randomised groups and quantitative analysis will be conducted in rstudio version . . ( - - ). continuous variables will be presented as means, standard deviation, median and interquartile range, meanwhile, categorical variables will be presented as frequencies and percentages. the randomised groups will be examined and compared for all variables. categorical variables will be evaluated using the chi-square test. continuous variables will be tested for normality and based on the distribution of the data, appropriate parametric or non-parametric tests will be used. for example, paired t test or wilcoxon test would be applied to assess the differences in baseline variables between both groups and between participants who completed the trial as well as the participants who will be lost to follow up. the primary and secondary outcomes (total and types of hypoglycaemic attacks) will be measured across the randomised groups and compared using the analysis of covariance (ancova), and the appropriate parametric or non-parametric tests dependent on the normality of distribution. subgroup analysis will also be performed using interaction terms in regression models. we will use logistic regression analysis to examine associations between the categorical outcome variable ( frequent vs infrequent hypoglycaemia episodes) and independent variables such as sex, age, educational level, living arrangements, duration of diabetes, number of current medications, experiencing previous hypoglycaemia, the status of self- monitoring of blood glucose, types of anti-diabetic medications, baseline hba c and interactions between the independent variables. the findings will be also presented as odds ratio and % confidence intervals. a p value of less than . will be considered statistically significant. hypoglycaemia rates will be described with kaplan-meier survival curves, considering the time to the first hypoglycaemic attack as the outcome measure. qualitative data analysis the interviews will be audio-recorded then transcribed and translated into the english language. we will use the thematic analysis approach to analyse the collected data for there is a need for protocol amendments through the embedded evaluation process, the changes will be discussed by the supervisory team and will be communicated in writing to the human research ethics committee of the university of lincoln and the institutional review board of kauh. upon completion of the study, we will provide the trial site with an executive summary of the findings in the form of a report. participants would be able to get the results of the study from their health care professionals at the trial site no later than one year after the end of data collection. we are planning to disseminate the study outcomes through peer-reviewed publications and presentations in conferences. we will comply with the authorship eligibility the sugar handshake intervention is designed to be pragmatic and to facilitate transferability of evidence into practice. therefore, pharmacists can easily deliver it to the patients in different working positions including hospitals and community pharmacies. moreover, the delivery of the sugar handshake intervention is cheap and will not cost an extra burden on patients. previous studies concerning the attitudes, religious beliefs, and self-management skills amongst patients with t dm helped in assuring the appropriateness of contextual and cultural delivery as well as the implementation of the study and the sugar handshake intervention. - using blood glucose/hypoglycaemia diaries to objectively report and measure several types of hypoglycaemia is another strength. this will facilitate a more accurate measurement of hypoglycaemic events where the concern that patients may forget to report the experienced episodes is reduced. a plausible limitation that warrants consideration is the short follow up duration ( weeks), which may make it difficult to examine the sustainability of the intervention effect. however, we anticipate that this duration will decrease the dropout rate. moreover, we expect the effect of our intervention to last up to at least six months as concluded by a previous trial. another concern is the enrolment of relatives into different groups upon randomisation, which will introduce contamination bias. therefore, if a patient happens to have a relative who has already participated in the trial, he would be excluded. additionally, participants may not fully adhere to the intervention during the follow-up period. for this reason, they will receive a phone call reminder at week six of enrolment. individualising the intervention according to each patient's lifestyle and potential causes of hypoglycaemia will enhance the adherence to the intervention as well. as this is an open-label study, performance bias and ascertainment bias may result from unblinding participants and the data collectors, respectively. participants in the control group may be less adherent to the trial protocol and more likely to withdraw from the trial. however, efforts will be made to standardise the trial protocol, frequency and time of follow up, and treatment of experienced hypoglycaemia across both groups to minimise performance bias. we also anticipate that the objective measurement of the outcomes would minimise ascertainment bias. the prevalence of diabetes in jordan has been growing rapidly to reach . % in . in light of the lack of awareness regarding diabetes diagnosis, causes, and management we would expect a further increase in the number of jordanians who are diagnosed with diabetes and who would suffer from diabetes-related complications. , while pharmacists are easier to access than physicians, a possible strategy to mitigate the burden of diabetes is to establish and support the pharmacist-led, patient-oriented services. international hypoglycaemia study group ihs. minimizing hypoglycemia in diabetes diabetes care adverse macrovascular events, and inflammation in the edinburgh type diabetes study. diabetes care association of hypoglycaemia and risk of cardiac arrhythmia in patients with diabetes mellitus: a systematic review and meta-analysis severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type diabetes: the atherosclerosis severe hypoglycemia and risks of vascular events and death effects of severe hypoglycemia on cardiovascular outcomes and death in the veterans affairs diabetes trial. diabetes care predictors of quality of life and other patient-reported outcomes in the panorama multinational study of people with type diabetes impact of symptomatic hypoglycemia on medication adherence healthcare resource use, direct and indirect costs of hypoglycemia in type and type diabetes, and nationwide projections. results of the hypos- study management of hypoglycemia in older adults with type diabetes sircar et al m. review of hypoglycaemia in the older adult: clinical implications and cardiovascular disease predicts severe hypoglycemia in patients with type diabetes diabetes management in older adults with chronic curr diab rep older adults: standards of medical care in diabetes- diabetes care the department of economic and social affairs of the united nations. world economic and social survey, : development in an ageing world the burden of disease in older people and implications for health policy and practice. the lancet an increase in prevalence of diabetes mellitus in jordan over years personalized diabetes management: moving from algorithmic to individualized therapy self-efficacy-focused education in persons with diabetes: a systematic review and meta-analysis the role of structured education in the management of hypoglycaemia pharmacy education in jordan: updates when are complex interventions 'complex'? when are simple interventions 'simple'? developing and evaluating complex interventions: the new medical research council guidance process evaluation of complex interventions: medical research council guidance spirit statement: defining standard protocol items for clinical trials hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes hypoglycemia event rates: a comparison between real-world data and randomized controlled trial populations in insulin- treated diabetes. diabetes ther intensive individualized reinforcement education is important for the prevention of hypoglycemia in patients with type diabetes the behaviour change wheel: a new method for characterising and designing behaviour change interventions better reporting of interventions: template for intervention description and replication (tidier) checklist and guide hypoglycemia and diabetes: a report of a workgroup of the american diabetes association and the diabetes care understanding the new hba c units for the diagnosis of type diabetes research council (mrc) guidance. mrc popul health sci res netw the prevention and handling of the missing data a comparative analysis of generalized estimating equations methods for incomplete longitudinal ordinal data with ignorable dropouts using thematic analysis in psychology community-based peer-led diabetes self- management effectiveness of hypoaware, a brief partly web-based psychoeducational intervention for adults with type and insulin- treated type diabetes and problematic hypoglycemia: a cluster randomized efficacy of structured education in patients with type diabetes mellitus receiving insulin treatment diabetes x-pert programme makes a difference the effect of an education programme (medias bsc) of non-intensive insulin treatment regimens for people with type diabetes: a randomized, multi-centre trial exclusion of older adults from ongoing clinical trials about type diabetes using shared decision-making to address possible overtreatment in patients at high risk for hypoglycemia: the veterans health administration's choosing wisely hypoglycemia safety initiative. clin diabetes publ am diabetes assoc a novel intervention including individualized nutritional recommendations reduces hemoglobin a c level, medication use, and weight in type diabetes. jmir diabetes time trends in diabetes mellitus in jordan between and health care and pharmacy practice in jordan pharmacist-led study in controlling hypoglycemia in older adults with type diabetes mellitus (rose-adam) we would like to acknowledge the university of lincoln and isra university for their support to conduct this study. we would also acknowledge the physicians and nursing staff working at kauh for facilitating recruitment and the study implementation. key: cord- -zem d y authors: thomaz ugliara barone, mark; bega harnik, simone; vieira de luca, patrícia; letícia de souza lima, bruna; josé pineda wieselberg, ronaldo; ngongo, belinda; cordeiro pedrosa, hermelinda; pimazoni-netto, augusto; reis franco, denise; de fatima marinho de souza, maria; carvalho malta, deborah; giampaoli, viviana title: the impact of covid- on people with diabetes in brazil date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: zem d y abstract the present study aims atidentifying main barriers faced by people living with diabetes in brazil during the covid- pandemic. methods in a convenience sampling study, data were collected from individuals, aged or above; . % female participants; . % t d and . % t d, between april nd and may th, using an anonymous and untraceable survey containing multiple choice questions (socio-demographic; health status and habits of life during covid- pandemic). relationship between variables was established using the multiple correspondence analysis technique. results . % of respondents reduced their frequency of going outside of their homes; among those who monitored blood glucose at home during the pandemic ( . %), the majority ( . %) experienced an increase, a decrease or a higher variability in glucose levels; . % postponed their medical appointments and/or routine examinations; and . % reduced their physical activity. t d, the youngest group, was more susceptible to presenting covid- symptoms despite not being testing; whilst the td group had higher frequency of comorbidities that are additional risk factors for covid- severity. conclusions this study provides a firsthand revelation of the severity of covid- on individuals with diabetes in brazil, altering their habits, which impacted their glycemia, potentially increasing their risk of poor outcomes if infected by sars-cov- . the outbreak covid- has led to an unprecedented global health crisis which is testing health systems' preparedness and ability to cope with a pandemic response [ ] [ ] [ ] [ ] . . brazilexperienced a similar situation. thefirst sars-cov- case was officially reported in december in wuhan,china, and rapidly spread in the entire country and beyond within days [ ] [ ] [ ] . the first suspected case in latin america was reported on january th in brazil and the first case confirmed in brazil on february th of [ , , ] . a series of measures were put in place p to prepare brazil for the anticipated health crisis prior to the declaration of covid- as being public health emergency of international concern, on january th [ ] , and then a pandemic, on march th [ ] . following these international alerts,less than a month after the first confirmed case, on march th, the brazilian ministry of health recognized that community transmission was already happening in brazil [ ] . infection by sars-cov- causes major disruptions and threats ,in addition to the loss of human lives, with case fatality rate ranging from . % in germany, to . %in italy [ ] , the impact of covid- is beyond imagination and is sparkling a global mourning,booming afeeling of unsafety and uncertainty. on june th, according to the world health organization (who), , , cases and , deaths duetocovid- were confirmed in countries [ ] . fcases and mortality in brazil reached , and , respectively,with a case fatality rate of . % [ ] . while this is the highest number of cases and one of the highest case fatality rate in latin america [ ] , scientists argue that cases and mortality are extremely underscored due to the low number of tests performed among other reasons [ , , , ] by possible - times the official reported figures [ ] . authors of the first chinese and italian reports alerted for the worse prognosis of individuals with diabetes and other noncommunicable disease (ncds), in comparison with populations of the same age group without those chronic conditions [ , [ ] [ ] [ ] [ ] . further retrospective studies have revealed that, within this group of patients, hyperglycemia was associated with higher severity and mortality rates [ , , , ] , for reasons under investigation [ , ] . additionally, usual comorbidities such as hypertension, cardiovascular disease, older age, and gender (male) also complement increased severity and mortality risks of individuals with diabetes hospitalized due to covid- [ ] . , with a prevalence as high as . million people or . % of the population between and years old, brazil is among the top countries with high prevalence of diabetes. diabetes leads g to more than , deaths yearly [ ] . brazil struggles with the continuous treatment routine of impacted populations; only . % are considered to be in target, having a glycated hemoglobin a c below . % ( mmol/mol) [ ] . consequently, . % of brazilians with diabetes belong to a subgroup more exposed to hyperglycemia , which makes them vulnerable to even higher risk of poor outcomes when infected by the sars-cov- virus. this state of affairs calls fordeep commitments from the public health in all its forms and a concrete alignment with the who. unfortunately, in the midst of the fight against this novel virus, brazil experienced a troublesome atmosphere of political disputes, blinding authorities to make swift decisions aligned with the global technical recommendations [ , , ] . this also harmed adjustments to continue the proper follow-up and management of other diseases, including both communicable and ncds. for these reasons, the present study aims to investigate challenges encountered by people living with diabetes in brazil during the covid- pandemic. data from individuals with diabetes were collected through an anonymous and untraceable survey containing multiple choice questions in portuguese. the authors shared this survey on social media including facebook, through their affiliated institutions, co-ligated or partner entities, and diabetes social media groups. hence, the convenience sampling nature of this study. in addition to being a person living with diabetes, individuals needed to be legally adults (above years old) and accept the terms to share anonymous and untraceable answers. survey responses were collected from april nd through may th. the first question provided a complete overview of the questionnaire and required confirmation of the heath conditon (diabetes) by the respondent. . this was followed by socio-demographic questions related to age, gender, state of residence, capital/country/coast, education level, number of people living in the household, and nature of the health system which could be public, private or both. subsequent questions served to identify the health status of the participants, asking about diabetes type, and presence and type of comorbidity. all remaining questions covered aspects attributed to the covid- pandemic: frequency of going outside, strategies to protect from infection when outside, noted changes in the glycemic levels, access to medical care, changes in eating habits and physical activity, changes in smoking and drinking habits, and suspected or confirmed covid- infection by the respondent or cohabitant family member. at the end of the survey, the respondent could leave a comment. several questions and their answers were regarding subjective perceptions, such as "my blood glucose increased", "i am eating more" or "i am exercising much less" than before the pandemic. therefore, answers should not be interpreted as objective measurements, but as subjective comparisons with the prepandemic states. a multivariate analysis of dimensions of covid- and types of diabetes (type diabetes -t d; type diabetes -t d; others: lada, mody, gestational; and unknown) was performed with multiple correspondence analysis (mca) in r (version . . ) and rstudio (version . . ) [ ] . the survey was answered by individuals, . % were female respondents, . % between and years old, . % of respondents were from southeast of brazil, and the main diabetes types were type ( . %) and type ( . %) (full socio-demographic profile in table ). among the main reported consequences of the covid- pandemic were: . % reduced frequency of going outside home (among them, . % never went outside since the beginning of the pandemic); among the ones who monitored their blood glucose at home ( . %), the majority ( . %) experienced a deterioration, which included: . % are reporting greater variability than before the pandemic, % higher glycemia and . % lower glycemic levels. moreover, . % postponed medical appointments and/or routine exams, and . % did not schedule a medical appointment since the onset of the pandemic. among recommended habits, slated for diabetes treatment, physical activity was most impacted, with a reduction reported by . % of the respondents ( . % with a slight reduction and . % with a great reduction). see table for habits and behaviors. regarding co-morbidities, for the current study and analysis, we opted to group them into the following: ) "mental health" which includes the following conditions: depression, anxiety, bulimia, anorexia and diabulimia; and ) "cardiovascular diseases" comprising : stroke, infarction, hypertension and dyslipidemia. two other groups were already established in the survey as a single answer, which had a parenthesis to facilitate comprehension, the "diabetes related complications" with: retinopathy, neuropathy and diabetic renal disease; and the "respiratory": asthma and copd (table ) . the analysis revealed the association between age and the occurrence of symptoms of covid- , type of diabetes and some of the co-morbidities evaluated (figure ). people with t d were among the youngest and appeared in proximity to mental health diseases category, but also close to the no-cardiovascular conditions, no-obesity and no-respiratory disease categories. they were alarmingly close to the category that, despite having symptoms of covid- , had no testing for sars-cov- . not measuring the blood glucose is close to t d and unknown diabetes type. t d, not surprisingly, was more associated than other types with older age, cardiovascular diseases and obesity. it is also worth noting that t d and older group were the closest to test positive for sars-cov- . in opposition, individuals who had symptoms of covid- and were not tested ( people or . %) presented higher proximity to increased blood glucose (figure ). measuring blood glucose was related with food consumption and working out, as depicted on figure . individuals that experienced decrease in blood glucose levels, increased physical activity and decreased food consumption. meanwhile, higher food consumption and reduced physical activity were associated with higher blood glucose levels. while it seems that the pandemic had a higher impact on habits and glycemic levels of t d individuals (right side of figure ), with significant perceived changes, t d respondents seem to have maintained most of their habits during this period. individuals who exclusively use the brazilian public health system (unified health system -sus), which serves more than % of the brazilian population [ ] (in our case, . % of the respondents), were who kept venturing out during the pandemic and experienced an increase of blood glucose levels, as shown in figure . t d individuals were the closest to the use of both health systems (sus and private) and also experienced higher glycemic variability (ups and downs). they had the ability to have friends or relatives to buy or collect their medicines and medical supplies. users of the private health system were closer to experience no glycemic changes during the pandemic, using their own stocks of medicine and medical supplies or ordering for home delivery from private pharmacies (figure ) . the results above unveil short, mid and long-term risks for individuals with diabetes in brazil. while the federal government and some states made initial commitments and plans [ ] , knowing the risks for poor prognosis among individuals living with diabetes and/or other ncds if infected by sars-cov- . our data revealed that implemented measures did not cover most of this population. the strategy to distribute medicines and medical supplies for days, as recommended by different organizations [ , ] , in order to avoid monthly trips were effective for only % of the . % who received their medication and supplies from sus (or . % of the total respondents). this provision of medicines and supplies for months, avoiding the monthly rounds to public primary healthcare facilities or pharmacies, seemed to be the one of the only specific policies to protect individuals with diabetes and others living with ncds in brazil [ , ] . although limited, this would at least protect them from encountering infected people seeking care. . meanwhile, at municipality level, certain locations successfully implemented alternative strategies, as hailed by one participant from an inland town: "my town adopted a delivery of medicine method for people with chronic diseases". according to our data, especially individuals w exclusively depended on sus were at higher risk, venturing out of home more often and experiencing an increase in blood glucose levels ( figure ). while differences would not be expected, since brazil prides itself for its universal health coverage, and most people, including the ones with private insurance, rely on sus to receive part or all their medicines and supplies. we hypothesise that this finding highlights the socioeconomic inequalities in the country, which obliges the less privileged to continue going to work during the pandemic and/or to access affordable food. . even though . % of the individuals reported having a family member or friend going monthly to public pharmacies on their behalf to collect medicines and supplies, . % went themselves, perhaps due to lack of direct support.. it is important to highlight that family member's or friend's support may reduce but not eliminate the risk of infection, especially if residing in the same location, acting as a potential vehicle of indirect transmission. another uncomfortable answer came from . % of the individuals who reported halting collection of their medicines and medical supplies and relying on personal stocks, which might be limited in quantity or expected to expire soon. this situation may place those who avoided leaving their homes during the pandemic in a risky untreated situation, a globally shared concern [ , , , , ] . while it is hard to predict social, economic and health impact of a pandemic, specialists alert to the consequences of implementing only light measures [ , , , , , ] , but, at the same time, also the harmful consequences of lockdowns, mobility restrictions and social distancing on the prevention and control of diabetes and other ncds [ , , ] . barone et al. [ ] reported an association between stricter measures against the pandemic and perceived challenges and fear in the diabetes community in south and central american, which, when disconnected from information and educational strategies, would increase the pressure on the health systems [ , ] . although decentralized (defined by states and municipalities) and delayed [ , , , , ] , the measures to contain the sars-cov- spread in brazil, and reflected on mobility reduction, was experienced by . % of this study's respondents in different degrees (with . % never going outside). differently from kluge et al.'s prediction [ ] , in our case it was not associated with increased consumption of alcohol, tobacco and unhealthy foods. notwithstanding, physical activity was affected, being reduced for . % of the respondents. other researchers have also reported physical activity reductions during the pandemic, and alerted for the potential negative consequences on metabolic, cardiovascular and musculoskeletal health [ , ] . these effects were observed even after short periods of inactivity, are hard to recover and, not only increase premature mortality, but also favors the development of diabetes chronic complications [ , ] . a strategy to minimize those consequences would be developing good channels and partnerships for informing these populations through the internet and tv broadcasting in a structured manner, focusing on preventive measures and maintenance or improvement of habits and behaviors, such as regular physical activity [ , , , , ] . this recommendation is compatible with the present findings where . % of the individuals maintained or increased their time watching tv and . % maintained or increased their time on the internet. regarding treatment, the covid- pandemic, as predicted and observed by different authors, is impacting availability and access to healthcare professionals (hcps) for the routine care of people with diabetes, since they relocated to emergency rooms, testing sites, icus and other services to attend infected individuals [ , , , , ] . covid- transmission was found to be high among hcps. . we investigated . % of the individuals who postponed their medical appointments and/or examinations. we attributed these results to shortage of hcps, as cited by individuals, reporting appointment cancelation or absence of s physician, or personal decision because of the fear of getting infected at a hospital or clinic. also identified, in other studies as one of the greatest fears of the population [ , ] . the potential consequence of this phenomenon of fear during the pandemic was reported in a pediatric emergency department, in italy, with reduction and delay in children's arrival, which included cases of severe ketoacidosis and hypoglycemia [ ] . although online consultation and other telemedicine strategies were not investigated profoundly in the present study, one of the respondents commented that he/she was having online medical appointments. brazilian laws and regulations became more flexible allowing this type of approach during the covid- pandemic [ ] . in alignment with other authors and international organizations, we highly recommend it [ , , , , , , ] , reinforcing primary healthcare's role during the pandemic through ensuring close and timely monitoring of people with diabetes and other ncds [ , , ] the results show thatall types of diabetes were close to additional risk factors for poor prognosis of individuals infected by sars-cov- . while t d and unknown diabetes type (figure ) appear near other ncds (especially cardiovascular and obesity) [ , , , , ] , t d and other types (lada, mody and gestational grouped) presented close proximity to glycemic variability (figure ) [ , , ] . therefore, we suggest that none of the types should feel safe. although, not surprising, t d was associated with " years and older" (figure ), and it is known that the covid- mortality and severity increase with age [ , , ] .it was unfortunate the proximity of individuals reporting increased blood glucose levels and the presence of covid- symptoms without testing (figure ). the global shortage of tests for sars-cov- poses a grand challenge [ ] [ ] [ ] , however, cognizant that high blood glucose increases the risk for infection severity and death [ , , , , , ] , early testing efforts are recommended in this group. in addition, supporting them in intensifying their diabetes self-care practices to quickly bring their glycemia back on track must be prioritized [ , , ] . figure depicts the importance of balancing food and exercise, since individuals who increased or decreased any of them experienced changes in their blood glucose levels, whereas those able to maintain exercise and food consumption avoided glycemic changes. while the present study focused only on diabetes, who's data show that other ncds serviced in similar health systems and pandemic environment, are facing comparable challenges [ ] . in terms of unattended needs of individuals with diabetes during this covid- crisis, brazil is not the only country with unaddressed demands. in a collection of testimonials from people with diabetes in different countries, the international diabetes federation exposed some similar issues whilst others different from the brazilian context [ ] . while the absence of specific measures to protect those with diabetes was reported in greece and spain, access to medicines was a challenge in zimbabwe, iran and india [ ]. however, countries like argentina, italy, portugal, and south korea seemed to have adopted measures that made people with diabetes feel safer [ , ] . it is urgent for brazil to follow international best practices and recommendations, since, as stated by the who regional office for europe, "the prevention and control of ncds have a crucial role in the covid- response and an adaptive response is required to account for the needs of people with ncds" [ ] . imitations of the present study, although efforts were made to disseminate the survey as much as possible, this study's sample neither reflects the proportion of brazilian population nor the fraction with diabetes. thus, it is a convenience sample, without post-stratification weights. questions about behaviors, habits and glycemic changes were subjective comparisons with the pre-pandemic state, therefore, we did not have access to objective data to validate the subjective responses. as an online survey, it is biased by individuals who have internet access. while % of the brazilian population have a college degree [ ] and . % have private health insurance [ ] , among the respondents of the present survey, . % had at least one college degree and only . % exclusively access care services through sus. other demographic limitations related to the age groups distribution, younger than the general population with the great majority of the respondents from sao paulo state, which would be about % of the country, not . % as in our group of respondents. we understand that one of the main factors leading to this bias is the network in which the authors are engaged, the geographic location of diabetes associations and the profile of their active members, tendency to have more individuals with t d than t d, mostly young and highly educated. ann additional limitation is the number of choices for each question and the aggregation made for analysis purposes. this includes the fact that if separated, diseases aggregated in the cardiovascular disease group, for example, could behave differently in terms of proximity to other factors; moreover, increase or decrease of the blood glucose, interpreted as distancing from the target, would in fact have led the glycemic to target, while the ones who successfully maintained the blood glucose in pre-pandemic levels, may have kept it out of target. as revealed for the first time in the current study, individuals with diabetes were not spared by the covid- pandemic in brazil. measures and adjustments lacked or were insufficient, paving the way to unhealthy and unsafe behaviors such as postponing medical appointments, reducing physical activity and refraining from collecting medication and supplies, which led to a high percentage of glycemic worsen reports. additionally, announced measures for prevention and mitigation of covid- consequences on this population, such as supply of medicines for months, worked just for a minority. in conclusion, we see a pressing need from the brazilian federal, states and municipal authorities to broaden the already implemented measures in order to reach more people, and partner with civil society, private sector and media channels to quickly improve the response and, this way, prevent a surge of individuals with diabetes infected by sars-cov- and of acute and chronic diabetes complications. among the priorities measures to keep individuals healthy is by ensuring their glycemia is on target and they are at home as much as possible. we recommend that the public and the private health systems maintain and strengthen programs for the continuity of care of individuals with diabetes and other ncds, and develop information and educational campaigns on how to access those measures. in addition to focusing on reducing the risk of infection and continuity of their healthcare, these measures should facilitate access to healthcare professionals' counseling for therapeutic adjustment. finally, as key measures we foresee are a) activemonitoring and response to communities' needs at primary heathcare level; b) high quality telehealth for consultations to monitoring and examining; c) distribution of medications and supplies for three or more months, ideally with home delivery; d) lab exams scheduled through home sampling, using mobile point-ofcare strategies or appointment in specific facilities with well established disinfection protocols. consequently, we believe that the pandemic's challenges can be lessened if appropriate measures protecting individuals with diabetes and other chronic conditions are adopted, and investments are not solely directed to purchasing mechanical ventilators and equipping tertiary care. epidemiology, public policies and covid- pandemics in brazil: what can we expect? revista de enfermagem uerj covid- in brazil: advantages of a socialized unified health system and preparation to contain cases. sociedade brasileira de medicina tropical covid- in latin america: the implications of the first confirmed case in brazil south america prepares for the impact of covid- characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet preparación y control de la enfermedad por coronavirus (covid- ) en américa latina covid- : towards controlling of a pandemic covid- in italy: momentous decisions and many uncertainties who. coronavirus disease (covid- ) pandemic the lancet. covid- in brazil report : estimating covid- cases and reproduction number in brazil pesquisadores estimam haver mais de , milhão de casos de covid- no brasil covid- infection in italian people with diabetes:lessons learned for our future (an experience to be used) care for diabetes with covid- : advice from china prevention and control of noncommunicable diseases in the covid- response clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study. the lancet association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes admission hyperglycemia and radiological findings of sars-cov in patients with and without diabetes glycemic characteristics and clinical outcomes of covid- patients hospitalized in the united states elevated glucose levels favor sars-cov- infection and monocyte response through a hif- α/glycolysis dependent axis hyperglycemia and the worse prognosis of covid- . why a fast blood glucose control should be mandatory clinical characteristics and risk factors for mortality of covid- patients with diabetes in wuhan, china: a two-center international diabetes federation prevalence of diabetes mellitus as determined by glycated hemoglobin in the brazilian adult population, national health survey an analysis and synthesis of multiple correspondence analysis, optimal scaling, dual scaling, homogeneity analysis and other methods for quantifying categorical multivariate data private health care coverage in the brazilian population, according to the brazilian national health survey. ciência & saúde coletiva paho. if i have diabetes, what do i need to know about covid- ? securing the safety net and protecting health during a pandemic: medicaid's response to covid- alterações no programa farmácia popular devido à situação de emergência de saúde pública decorrente do coronavírus (covid saúde amplia entrega de remédios nas farmácias de alto custo para prevenção do coronavírus covid- and diabetes prevention and management of covid- among patients with diabetes: an appraisal of the literature delayed access or provision of care in italy resulting from fear of covid- covid- and endocrine diseases. a statement from the enfermedad por coronavirus (covid- ) en américa latina: papel de la atención primaria en la preparación y respuesta public health measures and the reproduction number of sars-cov- covid- impact on people with diabetes in the south and central america deep impact of covid- in the healthcare of latin america: the case of brazil social isolation during the covid- pandemic can increase physical inactivity and the global burden of cardiovascular disease risk of increased physical inactivity during covid- outbreak in older people: a call for actions managing covid- in low-and middle-income countries what is the role of primary health care in the covid- pandemic? practical recommendations for the management of diabetes in patients with covid- . the lancet the silver lining to covid- : avoiding diabetic ketoacidosis admissions with telehealth coronavirus infections and type diabetes -shared pathways with therapeutic implications ensuring people-centred diabetes care during the covid- pandemic experiences from portugal beyond the virus: ensuring continuity of care for people with diabetes during covid- . primary care diabetes obesity and covid- severity in a designated hospital in shenzhen, china. diabetes care covid- and diabetes: knowledge in progress type diabetes and covid- : preliminary findings from a multicenter surveillance study in the u.s. diabetes care critical care utilization for the covid- outbreak in lombardy, italy clinical considerations for patients with diabetes in times of covid- epidemic world health organization, rapid assessment of service delivery for ncds during the covid- pandemic covid- : perspectives from people with diabetes education at a glance . country note brazil the authors acknowledge vanessa pirolo's support and assistance sharing the survey through her network and the non-governmental organizations adj diabetes brasil (adj), institute for children with diabetes (icd), brazilian diabetes society (sbd), brazilian hypercholesterolemia association (ahf), fórumdcnts and their member and partner entities for assisting in sharing the survey and providing general support. key: cord- -hb bsb q authors: khader, mohammed abdul; jabeen, talha; namoju, ramanachary title: a cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: hb bsb q background and aims: uncontrolled diabetes has been associated with poorer clinical outcomes in covid- . we aimed to evaluate and assess the impact of covid- pandemic on management of diabetes and challenges faced by people with diabetes in india during and after the lockdown phase. methods: a cross-sectional study based on an online questionnaire survey was designed. the questions collected socio-demographic details, medical and social history, and impact of the pandemic on medical and social life from participants. linear regression was employed to evaluate association of different parameters with the change in glycemic levels. results: the frequency of clinical visits during the covid- pandemic were reduced in . % of participants. . % of participants were able to monitor their blood glucose levels (bgls) in which . % ( . %, . %, and . %) participants experienced an increase in bgl (mild, moderate, and severe respectively). only . % of participants possessed the digital glucometer at home. . % of participants reported a decrease in physical activity while . % reported an increase in food intake. . % of participants were able to buy all medicines and . % were gone for virtual consultations while . % reported that they didn't have access to healthcare services. overall, . % participants experienced disruption in therapy. a highly significant correlation (r = . , p = . ) was found between increasing age and reporting of higher bgls. conclusion: this study provides a firsthand evidence of major disruption in diabetes care activities during and after the lockdown phase in india and increased risk of poorer clinical outcomes, if infected by sars-cov- . the coronavirus disease (covid- ) , a pandemic originated from china as a cluster of unknown pneumonia cases is continuing to wreak havoc globally [ ] . as of july , the world health organization (who) has documented , , positive covid- cases and the death toll stood at , . india, with no exception, is ringing high alarm bells to the outbreak. currently, india has a load of , , covid- cases, making it the worst-hit nation of asia and third worst-hit nation in the world after the united states and brazil [ ] . the outbreak is frequently testing the preparedness of health services and their ability to cope with a pandemic response [ ] . the first confirmed case of sars-cov- positive in india was reported on th january. following the drastic growth in daily case counts, the government had drawn up plans to deal with a worsening of the pandemic in the country. a series of lockdowns starting from th march were imposed on people in the country to break the chain of virus transmission [ ] . further, united nations and who have praised india's response to the pandemic as 'comprehensive' and 'robust'. however, since the start of "unlocking" and easing of restrictions from june st , india is witnessing an exponential rise in covid- cases indicating the possibility of 'community transmission' [ ] . accumulating evidence suggests a high risk of becoming severely ill with the coronavirus in people with increasing age and pre-existing comorbidities [ , ] . the mortality rate due to covid- in india is very low (i.e. . %) and interestingly majority (nearly %) of deaths are being observed in those having comorbidities [ ] . among all, diabetes found to pose a particular adverse risk for covid- infection [ ] . uncontrolled diabetes compromises innate immunity, the first line of defense against sars-cov- [ ] . this results in disruption of cell-mediated immunity, diminished lymphocyte transformation, impaired leukocyte function, greater viral replication in pulmonary epithelial cells, and consequent pneumonitis [ ] . since people with diabetes are at increased risk of morbidity and mortality associated with sars-cov- infection, their routine care, and monitoring are highly important [ ] . apart from the risk of covid- infection, a poorly controlled diabetes has the potential to root life-threatening complications like macrovascular diseases (angina pectoris, myocardial infarction, stroke, peripheral artery disease), microvascular diseases (retinopathy, nephropathy, and neuropathy), and immune dysfunction (more susceptible to bacterial and fungal infections) [ ] . with medical focus largely centered on covid- , the clinical support needed by patients living with non-communicable diseases (ncds) is getting severely affected [ , ] . treatment delays, discontinuation of routine care, services, and uncertainty around medicine availability have left them more at risk than ever. a survey of countries by the who reported dramatic curtailment of health services for patients living with ncds during the covid- pandemic. it was reported that diabetes treatment has been partially or completely disrupted in % of the countries surveyed. the lower-income countries and countries moving in to transition towards the community transmission are being majorly affected [ ] . a recent study in the brazilian population revealed the impact of covid- on diabetics [ ] . india harbors million diabetes patients, which makes it the second most affected nation in the world, after china. the number is projected to grow million by as per the international diabetes federation [ ] . on the other hand, only a few papers have discussed the association between the covid- outbreak and its impact on diabetes care in india. however, these studies had a relatively smaller sample size and were primarily conducted during the period of nation-wide lockdown [ ] [ ] [ ] [ ] . by virtue of being with a higher prevalence of diabetes and a hasty upsurge in covid- cases during the unlocking phase, and with their overlapping on morbidity and mortality of people, it is essential to study the impact of covid- on diabetic care in india and helps improvise the preparedness for current and future thereat imposed by covid- . keeping the above points in view, this study was designed to evaluate the impact of covid- pandemic on medical treatment, routine care services, and challenges faced by people living with diabetes in india. a cross-sectional study based on an online questionnaire survey was designed to assess the impact of covid- on the medical treatment of diabetes people. the study was conducted in between : ist, june th , , and : ist, july th , . people with diabetes were invited for the study through social networking platforms including facebook, whatsapp, linkedin, text message, through their affiliated institutions, and diabetes social media groups. the questionnaire consisted of multiple choice questions in english and telugu. the survey initiation clearly stated the right of the individuals to participate or not to participate in the survey. all the participants enrolling must have to fill the informed consent form. inclusion criteria -people who are diagnosed with diabetes -any gender -age more than years exclusion criteria -not able to provide informed consent for the study the questionnaire consisted of mainly domains: a) socio-demographic details, e.g., subject's age, gender, state, city, town, educational qualification, financial income; b) medical and social history, e.g., type of diabetes, comorbidities, smoking, and drinking habits; c) impact of covid- outbreak on their medical and social life, e.g., frequency of clinic visits, changes in glycemic levels, digital glucometer at home, access to health care services, changes in the eating habits and physical activity, changes in drinking and smoking habits, online consultations, the reason for cancellation or postponement. in the end, a blank j o u r n a l p r e -p r o o f space was given to leave a comment. the questions were designated to relate the current situation of participants "during" the pandemic, to "before" the pandemic. descriptive analysis was computed in terms of mean value ± (standard deviation) for continuous variables and frequency (percentage) for categorical variables. student's t-test was used to examine the association between continuous variables. multivariable logistic regression analysis was used to adjust for the effect of cofounders when appropriate to determine the association of binary outcomes. linear regression was employed to evaluate the association of different parameters with the change in glycemic levels. a p-value of < . was considered statistically significant. all statistical analyses were done using the spss statistic . (ibm spss statistics, new york, united states) database. bar diagrams, tables and charts were created using microsoft excel version to depict percentages, and averages. a total of responses obtained in the study duration and responses excluded due to the incomplete information. a total of responses then assessed for the study. the majority of participants were male ( . %) and belonged to the age group of - ( . %). the mean age was . years. the participants were from different states in india -telangana, andhra pradesh, tamil nadu, maharashtra, karnataka, kerala, delhi, punjab, and rajasthan., of which, . % comprised from telangana state (hyderabad= . %). a significantly higher number of participants lived in urban localities ( . %). the highest levels of education for most of the participants were graduation ( . %) and secondary ( . %). % of participants had a monthly income ₹ > , and . % had a monthly income in the range of ₹ , - , . people with type- diabetes were predominant in the study ( . %). comorbidities were present in . % of the participants. the most common comorbidities were hypertension and dyslipidemia. . % and . % of participants had smoking and drinking habits respectively. the complete socio-demographic profile of the participants is shown in table . impact of epidemic on medical treatment and social life of people with diabetes: the frequency of clinical visits of participants significantly decreased as compared to prepandemic period (fig. . a) : ( . %) participants didn't visit the clinic till now i.e., from march nd to june th ; ( . %) participants visited once in three months; ( . %) visited once in two months; and ( . %) visited once monthly. ( . %) participants monitored their blood glucose level (bgl), either with digital glucometer in-home or through blood samples in a lab or a clinic (fig. . b) in which . % ( . %, . %, and . %) participants experienced an increase in bgl (mild, moderate, and severe respectively) (fig. . a) . ( . %) possessed blood glucose measuring device (digital glucometer) at home (fig. . c) . the covid- pandemic disrupted physical activity and food intake. ( . %), ( . %) and ( . %) participants showed a decrease, no change, and increase in physical activity respectively than before the pandemic ( fig. . d) . ( . %), ( . %), and ( . %) participants showed an increase, no change, and a decrease in food intake respectively than before (fig. . e) . the epidemic increased virtual consultations. ( . %) participants used the virtual platform to follow up with doctors during the study period, while ( . %) expressed that they used the virtual platform before the pandemic also (fig. . b) . further, the covid- pandemic disrupted the purchase of medicines. ( . %) participants purchased all the medicine. ( . %) did not buy due to unavailability of medicines, ( . %) did not buy due to financial constraints and ( . %) felt purchase of medicines difficult due to fear of corona ( fig. . f) . participants allowed to choose more than one reason in case of multiple answers applied. among participants, a total of ( . %) didn't have access to healthcare services as before the pandemic (fig. . g) . the major reasons for cancellation and postponement of appointments with doctors were a) fear of getting infected with covid- - ( . %), b) absence of physician from the clinic - ( . %), c) lack of communication with clinics - ( . %), and d) financial constraints - ( . %). participants were asked to choose more than one reason in case of multiple answers applied (fig. . h) . a total of ( . %) expressed that the covid- pandemic disrupted their therapy [majorly - ( . %) and slightly - ( . %)] (fig. . c) . further, logistic regression analysis showed a significant correlation with regard to increasing age and reporting of an increase in bgls (r= . , p= . ), (fig. . c) . this study provides the firsthand evidence of major disruption in diabetes care activities during and after the lockdown phase in india. with india witnessing exponential growth in covid- cases since the start of unlocking [ ] , the challenged healthcare resources laid down falling short to meet the needs of the entire population, including individuals with diabetes. in our survey, we found the majority of people irrespective of being in urban or rural localities, were not able to follow up with doctors. however, people living in rural areas were found to have an additional level of difficulties through traveling, making it more inconvenient for them to see a doctor. with global priorities set to contain the spread of the virus, the absence of physicians for people having ncds and fear of getting infected with covid- are playing key roles in the disruption of diabetes care. other major factors identified were financial constraints and altered work-timings of clinics due to pandemic. the majority of participants monitoring their bgl either at home/laboratory/clinic said that they observed a spike in their bgl. our data mainly consisted of people having type- diabetes ( . %). recent literature has mainly focused on disrupted glycemic control among type- diabetes people [ , ] . therefore, irrespective of the type of diabetes, there is a need to monitor bgls in this population. diabetes people infected with sars-cov- had a more than triple mortality rate of % in comparison to % in those without diabetes [ ] . uncontrolled diabetes has the potential to results in long-term complications, if not addressed at the earliest [ ] . % of participants had digital glucometer at home while % didn't have. this was not studied previously. in the times of covid- , the use of such devices are a must for diabetes people and they should be educated about its importance. pharmacists working in clinical settings and dispensing areas can play a great role in patient education about such devices. concerning authorities should make sure that no shortage of such devices happens. regardless of the existence of pandemic, such devices help diabetics for selfmonitoring and self-care [ ] . with no doubts, lockdown measures and mobility restrictions were found effective to control the spread of covid- [ ] , but, at the same time, showing their harmful consequences on prevention and control of diabetes and other ncds [ ] . barone et al, reported that stricter measures against the pandemic may lead to present and future severe impact on diabetes care in south and central america [ ] . though mobility restrictions are eased during the postlockdown phase in india, fear of getting infected with covid- and "work from home" scenario is keeping people confined to their homes only. . % of participants experienced a decrease in their physical activity and . % had an increase in their food intake than before. a decrease in physical activity of diabetes people ( . %) was also reported by barone et al. the study also reported an increase in food intake ( . %) among diabetics. in line with recommendations suggested by barone et al, internet and television broadcasting can be used as an effective medium to create awareness among people of habits and behaviors, such as regular physical activity [ ] . however, the use of television by participants was not investigated in the current study. the proportion of people using virtual consultation platforms with doctors has significantly increased. only . % of participants said of using virtual consultation before while it got increased to . % during the pandemic. a pilot study from government medical university reported teleconsultations were given by ophthalmologists during covid- lockdown in india [ ] . overall, . % of participants said not having access to overall healthcare services as before and . % said pandemic has disrupted their therapy. increased age people were found to have the worst glycemic control (p= . ). the presence of comorbidities and behavioral habits predicted increase bgls, but did not reach statistical significance. many participants in the comment section provided at the end said that they are more stressed about uncertainty prevailing due to pandemic and waiting for normalcy to return. le joesnen et al, reported an increase in covid- specific worry among diabetics in denmark [ ] . the results from our survey revealed flaws in government measures, healthcare policies to protect this vulnerable group of people from public health emergency due to the covid- pandemic. though a lot of plans are being made by the government and states [ ] , they did not cover most of this population. we found people with old age are those having a major disruption in the bgls. since the risk of becoming severely ill with sars-cov- appears to be high in people with increased age and poorly controlled diabetes, disturbed diabetes care is paying the way for the consequences that might be worse than the pandemic itself. this may also result in the diabetes population in india projected to grow million by much sooner than predicted earlier. as india has entered into the "unlock" phase, an increase in covid- caseload is resulting in an additional disruption in care for diabetes people. since many other countries have also entered into the "unlocking phase", an immediate call to look for people having diabetes seems eminently appropriate. self-monitoring of bgls through devices like digital glucometer is essential. availability of medicines, diagnostic tools shouldn't get under stocked. diabetes people should be educated about the symptoms of hyperglycemia, essentially in times when their visit to doctor's in-person appears risky and difficult. though the use of telemedicine platforms is growing with much attention in india since the beginning of the pandemic, many milestones are still needed for its acceptance among people [ ] . since many people in the survey said fear of getting infected with covid- and the absence of physicians from clinics were the main reasons for therapy disturbance, clear knowledge and understanding of people about telemedicine will provide greater convenience while not having to expose themselves to infection in an in-person clinic. broader strategies to protect people's jobs and economic crises arising from pandemic are essential. the main limitations of our study includes a) our sample is not reflective of the diabetic population of india. we had more than two-third participants from southern india ( . %) therefore the geographical distribution could lead to varying responses. b) all responses have been collected through online-mode without having access to objective data to validate the subjective responses and c) only people having internet facilities were able to participate in survey while india has . % of people who don't have access to the internet. our study revealed a severe disruption in diabetes care activities during and after the lockdown phase in india. the covid- pandemic has created additional challenges for the healthcare sector and people with diabetes are not spared from this. though the lockdown measures are eased, the ongoing pandemic continues to devastate the healthcare services for ncds. considering more severe symptoms and complications of sars-cov- in diabetics; disrupted glycemic control, physical inactivity and altered food consumption are paying the way for consequences that may be worse than the epidemic itself. india is having the second largest diabetes population globally and need an additional set of measures to be implemented soon. teleconsultation, use of digital devices, minimizing sedentary behavior, and home delivery of medicines should be encouraged among people with diabetes and ncds. the authors received no specific funding for this work. the authors reports no conflict of interest. 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estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: a simulation model using multivariate regression analysis covid- impact on people with diabetes in south and central america (saca region) teleconsultation at a tertiary care government medical university during covid- lockdown in india -a pilot study diabetes and covid- : psychosocial consequences of the covid- pandemic in people with diabetes in denmark-what characterizes people with high levels of covid- -related worries telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians table : socio-demographic profile and health status of the participants (n= ) we are immensely grateful to all the participants who took part in the survey. we thank our colleagues who greatly assisted the research. we thank dr. laeeq ur rehman who helped to distribute the anonymous survey to all diabetic groups and target physicians. we thank our friends across the states in helping us to distribute the survey platform to diabetics. all authors (akm, tj and rn) contributed equally to the designing of study, acquisition and analysis of data, preparation, revision and final version of approval of the manuscript. all authors have read and consented to the manuscript. j o u r n a l p r e -p r o o f a cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in india.abdul khader mohammed , pharmd, talha jabeen * , pharmd and ramanachary namoju , ms.affiliations: key: cord- - f wq authors: ory, marcia g.; lee, shinduk; towne, samuel d.; flores, starr; gabriel, olga; smith, matthew lee title: implementing a diabetes education program to reduce health disparities in south texas: application of the re-aim framework for planning and evaluation date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: f wq health disparities in diabetes management and control are well-documented. the objective of this study is to describe one diabetes education program delivered in the united states in terms of the re-aim (reach, effectiveness, adoption, implementation, and maintenance) planning and evaluation framework. questionnaires, clinical data, and administrative records were analyzed from adults with diabetes living in south texas, an area characterized by high health disparities. the diabetes education program delivered was a professionally led -month program involving h of in-person workshop education followed by quarterly follow-up sessions. changes in average blood glucose levels over the past months (e.g., a c levels) were the primary clinical outcome. descriptive and multiple generalized linear mixed models were performed. this community-based initiative reached a large and diverse population, and statistically significant reductions in a c levels (p < . ) were observed among participants with type diabetes at months. these reductions in a c levels were sustained at -, -, and -month follow-up assessments (p < . ). however, considerable attrition over time at follow-up sessions indicate the need for more robust strategies to keep participants engaged. for this diabetes education program, the re-aim model was a useful framework to present study processes and outcomes. health disparities are often geographically bound and occur more frequently in impoverished populations characterized by low socio-economic status and a dearth of available healthcare resources [ ] [ ] [ ] [ ] . the u.s.-mexico border is impacted by extremely high disparities in income, education, and healthcare access, and these social determinants of health make this region among the nation's figure illustrated the counties formally included in the healthy south texas initiative [ ] , and the counties in which the diabetes education program was offered were marked with a red dot. counties along the us-mexico border were included, as well as areas adjacent to border counties, which were all referred to as south texas. including urban, small town, and rural areas, the overall estimated population in these counties in was approximately . million, and these areas were among the most impoverished in the nation in terms of socioeconomic status and lack of healthcare services [ , ] . as a community-driven initiative, inclusionary criteria were broad with the intent of serving those both directly and indirectly involved in a person's diabetes prevention and management. while the focus was on adults with type diabetes, persons with pre-diabetes and type diabetes were invited, as well as family members or friends providing care for persons with diabetes. as indicated in figure , the formal diabetes education program was offered in of the south texas counties in two primary hubs clustered around nueces and hidalgo counties. given the community-based nature of this initiative and the desire to reach as many participants as possible to show widespread program penetration, participants were recruited from a variety of sources including screenings at health fairs, referrals from healthcare facilities, outreach to community partnerships with flyers and other social media, and self-referrals. although there was no attempt to standardize referral sources, which differed by organizational sponsorship and location, promotional materials (e.g., flyers) were standardized with a uniform healthy south texas brand. the diabetes education program was a recognized american diabetes association (ada) program that was professionally led but also included community health workers for outreach and programming assistance [ ] . all ada-recognized programs provided quality education for people with diabetes and followed the national standards for diabetes self-management education and support (dsmes) guidelines [ ] . ada-recognized diabetes education programs were eligible for reimbursement through many federal and private u.s. insurers [ ] . offered in both spanish and english, the program consisted of hours of face-to-face educational workshop sessions led by at least one trained health professional (e.g., registered nurse (rn), registered dietician (rd), pharmacist, or certified diabetes educator). workshop sessions were followed with brief (e.g., - min) in-person individualized follow-up educational and support sessions offered on a quarterly basis for a year. focal workshop topics included a discussion of, as well as hands-on experiential learning about what diabetes is, blood glucose monitoring, given the community-based nature of this initiative and the desire to reach as many participants as possible to show widespread program penetration, participants were recruited from a variety of sources including screenings at health fairs, referrals from healthcare facilities, outreach to community partnerships with flyers and other social media, and self-referrals. although there was no attempt to standardize referral sources, which differed by organizational sponsorship and location, promotional materials (e.g., flyers) were standardized with a uniform healthy south texas brand. the diabetes education program was a recognized american diabetes association (ada) program that was professionally led but also included community health workers for outreach and programming assistance [ ] . all ada-recognized programs provided quality education for people with diabetes and followed the national standards for diabetes self-management education and support (dsmes) guidelines [ ] . ada-recognized diabetes education programs were eligible for reimbursement through many federal and private u.s. insurers [ ] . offered in both spanish and english, the program consisted of h of face-to-face educational workshop sessions led by at least one trained health professional (e.g., registered nurse (rn), registered dietician (rd), pharmacist, or certified diabetes educator). workshop sessions were followed with brief (e.g., - min) in-person individualized follow-up educational and support sessions offered on a quarterly basis for a year. focal workshop topics included a discussion of, as well as hands-on descriptive statistics (mean and standard deviation or frequency and percentage) were used to describe the characteristics of participants. not all implementation sites collected the exact same set of variables; thereby, the descriptive statistics reflected available data (i.e., not all variables had the same number of missing cases). bivariate analyses (e.g., independent t-tests or chi-square tests) were performed to compare the characteristics of participants recruited during the first biennium and second biennium. next, retention rates were estimated for each follow-up session. as a part of retention analysis, characteristics of participants who attended and did not attend each follow-up session were described and were then compared using bivariate analyses. this study used data collected between september and december . although having four additional data collection months after the second biennium ended in august allowed for more follow-ups, not all participants had an opportunity to complete all their follow-up sessions. intervention delivery dates were used to identify and exclude participants from the retention analyses based on their eligibility to participate in the follow-up. for example, participants who participated in the workshop after june were excluded from the retention analyses for the -month follow-up. similarly, participants who participated in the workshop after march were excluded from the retention analyses for the -month follow-up; and those who participated in the workshop after december were excluded from the retention analyses for the -month follow-up. multiple generalized linear mixed models with participant-level random intercepts were fitted to examine changes in a c level over time among participants with pre-diabetes or type diabetes. persons with type diabetes (n = ) or gestational diabetes (n = ) were not included in the regression models due to small sample sizes. separate models were performed for the first and second biennia. the first set of models examined changes in a c levels over time in participants with type diabetes (n = in the first biennium and n = in the second biennium). the second set of models examined changes in a c level over time in participants with pre-diabetes (n = in the first biennium and n = in the second biennium). the third set of models examined any differences in the changes in a c levels over time based on diabetes type (pre-diabetes or type diabetes) (n = in the first biennium and n = in the second biennium). the next set of models examined changes in a c level among participants with type diabetes by their baseline a c level (i.e., . - . %, . - . %, . - . %, . - . %, . - . %, . - . %, and . % or higher) (n = in the first biennium and n = in the second biennium). in addition, a separate regression model was used to examine any racial/ethnic differences in changes in a c level (n = in the first biennium and n = in the second biennium). all regression models controlled for covariates including age, sex, race/ethnicity, education, language, and baseline bmi category. given that there were only participants reported speaking "other" as their primary language, they were excluded from the regression analyses. a significance level of . was used. this study involved retrospective reviews and analyses of limited data, and this study was reviewed and approved by the institutional review board at texas a&m university (irb - d). results were presented based on the five re-aim elements to provide a case study of this applied research about diabetes self-management education [ ] . reach was defined as "the absolute number, proportion, and representativeness of individuals who are willing to participate in a given initiative, intervention, or program, and reasons why or why not" [ ] . the number of persons who participated in the program and their general characteristics were tracked (table ). the majority of program participants were aged between and years ( . %), female ( . %), hispanic ( . %), and had high school or less education ( . %). most participants reported english as their primary language ( . %) ( table ). the intervention could be attended by individuals with pre-diabetes or diabetes as well as their family and friends. among the program participants with a recorded diabetes type, nearly % had pre-diabetes and more than % had type diabetes. the mean a c level was . % among those with pre-diabetes, . % among those with type diabetes, and . % among those with type diabetes. * p < . ; ** p < . ; a . p-values from bivariate analyses (e.g., independent t-tests or chi-square tests) comparing the characteristics of participants recruited during the first biennium and second biennium; b . chi-square comparison was performed after excluding "other" language (n = ); c . in total, . % of diabetes type records were missing, and frequency and percentage were calculated based on available data (n = ); d . mean and standard deviation of baseline a c percentage measures were estimated among those with pre-diabetes and type and type diabetes. bmi, body mass index. a c, average blood glucose level over the past months. there were statistically significant differences in characteristics of the participants recruited during the first and second biennium (table ) , indicating changes in program participant profiles and expanded program reach. compared to participants recruited during the first biennium, those recruited during the second biennium tended to be younger ( . % vs. . % aged - years), normal or overweight ( . % vs. . %), and not knowing their diabetes type ( . % vs. . %) ( table ) . in addition to considering initial recruitment, it was important to assess population representativeness over time. the program consisted of an educational session and four quarterly follow-ups to track behavioral goals and clinical outcomes. however, less than % of participants attended the first scheduled quarterly follow-up session at months, and the attendance rate for the subsequent follow-up sessions further decreased to . % at months, . % at months, and . % at months. the attendance rates at and -month follow-up sessions were higher during the second biennium than during the first biennium ( . % vs. . % at months and . % vs. . % at months). table shows the number and characteristics of overall program participants who attended and did not attend at each follow-up assessment. for all four follow-ups, retention rates were higher among those in the older age group, females, non-hispanic individuals, those with more than a high school education, and those whose primary language was spanish ( table ) . retention rates tended to be lowest for those with bmis classified as being underweight (table ) . among participants with type diabetes, those not attending a follow-up session at any given time point had significantly higher baseline a c levels than those who attended the follow-up session ( table ) . among participants with pre-diabetes or type diabetes, no statistically significant differences were observed based on baseline a c level attending a follow-up session at any given time point (table ). at the -month follow-up, the retention rate was significantly different based on participants' diabetes type ( table ). the retention rate was highest among those with pre-diabetes ( . % at months) and type diabetes ( . %), followed by those with type diabetes ( . %) and those who were unaware of their diabetes type ( . %) ( table ). however, the association between retention rates and diabetes type was not statistically significant at subsequent follow-ups (table ) . effectiveness was defined as "the impact of an intervention on important individual outcomes, including potential negative effects, and broader impact including quality of life and economic outcomes; and variability across subgroups (generalizability or heterogeneity of effect)" [ ] . this study evaluated changes in a c level among participants from baseline to each follow-up time point. in both the first and second biennium, a statistically significant reduction in a c level was observed among participants with type diabetes at the -month follow-up (b = − . , p < . in the first biennium and b = − . , p < . in the second biennium), and this a c level reduction was sustained at the -month (b = − . , p < . and b = − . , p < . ), -month (b = − . , p < . and b = − . , p < . ), and -month (b = − . , p < . and b = − . , p < . ) follow-up. for example, for participants with type diabetes who joined during the second biennium, the average a c level dropped from . % at baseline to . % at months, and this a c level reduction was sustained at subsequent follow-ups ( . % at months, . % at months, and . % at months). on average, participants with pre-diabetes had a c levels that remained controlled (< . %) from baseline to the subsequent follow-ups. for example, in the first biennium, a statistically non-significant reduction in a c level was observed among participants with pre-diabetes at all follow-ups (b = − . and p = . at months; b = − . and p = . at months; b = − . and p = . at months; and b = − . and p = . at months). participants who had type diabetes showed significantly greater reductions in a c level than those with pre-diabetes (p < . for the interaction term between time and diabetes type in both the first and second biennia) ( figure ). table . characteristics of the program participants who attended and did not attend -, -, -, and -month follow-up assessments. p-values from bivariate analyses (e.g., independent t-tests or chi-square tests) comparing the characteristics of participants who attended and did not attend the follow-up session; e . excluded participants who reported "other" primary language to prevent possibility of identifying the individuals; f . excluded participants who reported having gestational diabetes to prevent possibility of identifying the individuals; g . high missing response rates and frequency and percentage were calculated based on available data (n = at months, at months, at months, and at months); h . mean and standard deviation of baseline a c percentage measures were estimated among those with pre-diabetes, type diabetes, or type diabetes. bmi, body mass index. a c, average blood glucose level over the past months. significant reduction in a c level was observed among participants with pre-diabetes at all followups (b = − . and p = . at months; b = − . and p = . at months; b = − . and p = . at months; and b = − . and p = . at months). participants who had type diabetes showed significantly greater reductions in a c level than those with pre-diabetes (p < . for the interaction term between time and diabetes type in both the first and second biennia) (figure ). (a) (b) figure . estimated changes in a c from baseline to , , , and -month follow-up after adjusting for age, gender, ethnicity, education, language, and baseline bmi category, by diabetes type and biennia: (a) first biennium; (b) second biennium. a c, average blood glucose level over the past months. bmi, body mass index. changes in a c values over time among participants with type diabetes were also examined based on baseline a c values. estimated changes in a c by baseline a c values show similar trends over time among the participants enrolled during the first biennium ( figure a ) and second biennium (figure b ). for both biennia, there was a statistically significant modification effect of the baseline a c level on changes in a c values over time (p < . for the interaction term between time and the baseline a c level in both the first and second biennia). participants with high baseline a c values (e.g., % or higher) achieved a decline in their a c values at the -month follow-up assessments and maintained during the subsequent follow-ups. the estimated a c level decline was most pronounced for those with highest baseline a c values (e.g., % or higher). on average, participants with controlled diabetes at the baseline remained in control during the subsequent follow-ups. level on changes in a c values over time (p < . for the interaction term between time and the baseline a c level in both the first and second biennia). participants with high baseline a c values (e.g., % or higher) achieved a decline in their a c values at the -month follow-up assessments and maintained during the subsequent follow-ups. the estimated a c level decline was most pronounced for those with highest baseline a c values (e.g., % or higher). on average, participants with controlled diabetes at the baseline remained in control during the subsequent follow-ups. in a separate regression model, which included the interaction term between time and race/ethnicity, there was no statistically significant differences in changes in a c values over time among participants with pre-diabetes or type diabetes (p = . in the first biennium and p = . in the second biennium). adoption was defined as "the absolute number, proportion, and representativeness of settings and intervention agents (people who deliver the program) who are willing to initiate a program, and why" [ ] . in lieu of being able to quantify adoption, the general adoption approach was described. the coastal bend health education center (cbhec) in corpus christi served as the healthy south texas regional headquarters. the texas a&m south texas center, mcallen campus, served as a second regional hub. while planning the intervention roll-out, a hub-and-spoke model was determined to be the most effective strategy in which a central "hub" supports multiple "spokes" in communities to provide a range of services. with this approach, cbhec and the mcallen campus identified other regional partners to help recruit and deliver the program. due to the staffing requirements (e.g., needing a health professional to lead the educational workshops and sessions), the program was not delivered in all counties; rather, it was more selectively offered around the two hubs-with the spokes representing adjacent service areas. in accordance with ongoing collaborative health promotion activities in their respective local communities, both cbhec and the mcallen campus were able to call upon their extended healthcare and public health networks for program delivery assistance. regional partners that helped deliver the program represented diverse community and clinical entities including community-based organizations, federally qualified health centers, hospitals, clinics, pharmacies, school districts, academic institutions of higher education, state agencies and not-for-profit social service organizations, behavioral health organizations, and city and county government offices. partnerships varied with some organizations assuming a fuller responsibility for delivering courses on their own, some helping with overall recruitment, and some solely offering physical space for classes. implementation was defined as "the intervention agents' fidelity to the various elements of an intervention's key functions or components, including consistency of delivery as intended and the time and cost of the intervention. adaptations are also included in this re-aim element" [ ] . as an ada-recognized program, there was a need to demonstrate that ada principles of diabetes education were being followed. this involved an annual review by a designated quality control coordinator to review delivery processes, certify them as compliant, or note aspects to be corrected. program standardization across sites was facilitated by having a centralized hub for training and data reporting, in coordination with the scientific-administrative oversight functions provided by healthy south texas leadership. cbhec trained staff in program delivery using a standardized program manual and holding periodic problem-solving feedback sessions with regional program managers and implementers. adaptations to the program were discussed with the evaluation team to enhance program reach and retention. for example, program staff reported that many participants found it difficult to attend a single-day, -h workshop. therefore, other options were offered such as spreading the workshop over multiple days in two -h sessions or four -h sessions. program costs were not tracked in the first biennium, but efforts were made to retrospectively estimate actual program costs based on personnel, supply and space costs toward the end of the second biennium. the program was estimated to cost between usd and per participant, albeit with substantial variation based on how established the program was delivered at different sites, methods of recruitment, and the number of participants in each class. a major indicator of program implementation was how many participants engaged in all program activities (e.g., the initial educational workshop plus four quarterly follow-up sessions to track behavioral goals and clinical outcomes over time). as seen in table , only about % of participants attended the first quarterly follow-up session at months, and attendance rates decreased for the subsequent follow-up sessions. given that process evaluation activities were initially built into the program evaluation, program staff were made aware of this issue concerning attendance. subsequent action was taken in an attempt to bolster follow-up rates. retention rates at and -month follow-up sessions during the second biennium were significantly higher than the rates during the first biennium (i.e., . % vs. . % at months and . % vs. . % at months). maintenance was defined at the individual level as "the long-term effects of a program on outcomes after a program is completed" and at the setting level as "the extent to which a program or policy becomes institutionalized" [ ] . at the individual level, the trajectory of a c level change over time during the -month intervention period has already been reported in the effectiveness section (figures and ) . at the setting level, programs included within the healthy south texas initiative were intentionally designed to be housed within and delivered by established community partners who could draw upon their existing networks to facilitate programmatic spread and sustainability. for legislative feedback purposes, the amount of actual and in-kind dollars the health science center leveraged during the first two biennia was calculated. from private and public sources, over usd , , was identified in direct support and in-kind dollars for the healthy south texas initiative (including delivery of the diabetes education program, as well as other disease prevention and health promotion activities) by governmental and nongovernmental entities. the program is still ongoing with a legislative commitment for a third biennium (september -august ), and program delivery remains a core function of the two regional hubs. the healthy south texas diabetes education program reached and benefitted large numbers of participants in a region with documented health inequities that have perpetuated health disparities [ ] . utilizing the re-aim framework for both planning and evaluation enabled the study team to describe this diabetes program in terms of its reach, adoption, implementation, effectiveness and maintenance [ ] , and explore the unique challenges faced when applying and assessing re-aim elements in community settings [ , ] . this community-based initiative reached a large and diverse population in this region, thus supporting the external validity of the positive results observed. the hispanic population accounted for over two-thirds of the total population in the service region [ ]; hence, the ability to provide the program in spanish was a critical element that enabled the program to reach this population. an estimated , persons were served in the first two biennia across a broader range of diabetes outreach and education activities implemented by the texas a&m health science center healthy south texas initiative, in which the diabetes education program was a single component. this initiative capitalized on its understanding of the local community and organizational context, which has been deemed critical for the implementation and dissemination of other health promotion programs [ ] . this enabled the implementation sites to draw upon highly visible stakeholders and their diverse relationships with community and clinical organizations for outreach and delivery. culture, language, and access to resources are known barriers to access to care in the hispanic population with type diabetes [ ] , and collaboration with diverse local community and clinical entities enabled recruitment of culturally competent staff and facilitators to reach the hispanic population, who are likely to be an underserved population in the region. this study has generated several general take-home messages to be considered before implementing future health promotion initiatives. foremost, program planners should conduct community needs assessments and/or engage stakeholders from the communities they wish to target during initial planning, when assessing feasibility, and when deciding which components to include (e.g., considering potential cultural competency considerations and the need to tailor materials). while research studies typically need to offer incentives for participant recruitment [ ] , the healthy south texas initiative promoted program adoption by providing sites with necessary materials and/or subcontracted for services, which allowed programs to be offered free to participants who may have otherwise lacked resources to pay for such services. this was a critical component that helped alleviate or limit the participants' financial burden as a major barrier to participation, particularly among the socioeconomically disadvantaged population. when considering the generalizability of this evaluation in future settings and populations, program implementers and other key stakeholders should consider this option, where possible, as it may determine whether or not participants can access similar services in other initiatives. balancing fidelity to program implementation with the need for adaptation remains challenging in translational research [ ] . over the past two biennia, many of the recommended re-aim strategies for improving the implementation processes were implicitly followed and should serve as explicit guideposts in future studies [ , ] . for example, some sites adapted intervention delivery modes and routinized follow-up reminder contacts. other sites switched the health professional type needed to lead workshops to accommodate local needs and preferences. for example, one hub determined that in their setting a registered dietician was preferable to a registered nurse, and the ada offered some latitude when selecting the specific type of health professional used to lead workshops without jeopardizing the ada-recognized status or program fidelity. of particular note, the high attrition rates for follow-up visits raises issues about the feasibility and appropriateness of the current diabetes education program structure. the first biennium was a learning curve for the problem facilitators and implementation sites, and additional activities (e.g., reminder calls) were considered and conducted to enhance follow-up rates in the second biennium. reviewing other successful chronic disease self-management programs [ ] , the difficulties of expecting the targeted population to consistently engage in intervention sessions over a -month period were recognized. hence, one major adaptation for future programming is to consider modifications of the current diabetes education program and/or the development of a new iteration of such a program with a shorter active intervention period. long-term supports are still valuable for participant success and should still be incorporated in some capacity (e.g., by their healthcare provider, virtually, telephonically). the effectiveness of the diabetes education program demonstrated significant decreases in a c levels over time which were clinically meaningful [ ] . however, a closer look provides guidance for future targeting, which is a major concern in intervention research [ ] . while reducing a c levels is a clinical goal for persons with elevated a c levels, targeting those with a c values of and above has greater potential to be most cost effective, given these a c levels are associated with the most diabetes complications and need for costly medical care [ ] . findings from our study indicate that self-management programs adhering to ada best practices can achieve large decreases in a c levels among this population. maintenance of individual and system-level outcomes is often the most challenging re-aim element to achieve [ , , ] . it is critical to be aware of how context can influence outcomes at both levels. the practical robust implementation and sustainability model (prism) framework, which is now an integral part of the re-aim framework [ ] , helps us understand the contributory role of recipients, implementation and sustainability, infrastructure, and the external environment. one successful maintenance strategy at the individual maintenance level was to pair the diabetes education program with opportunities for class-based exercise programming throughout the year. based on feedback from program managers, participants seemed to enjoy these sessions and kept them engaged in the diabetes education program. additionally, the diabetes education program was seen as a core component of the two healthy south texas regional hubs, and organizational efforts are underway to build capacity and support for continued delivery through a network of concerned partners. in the current third biennium of state funding (september -august ), program staff are fully aware of the importance of context during these unprecedented times. thus, different options for long-term sustainability are being explored, noting that the current covid- crisis may make future state support less likely due to budgetary considerations [ ] . toward this end, strategies for defining and promoting the value proposition of this and other health education programs are being formulated. for example, fee-for-service options, seeking insurance reimbursement for recognized diabetes management programs, and/or providing the program for a modest charge to community or healthcare organizations as a community benefit are being investigated. to assist in making a value proposition based on the potential return on investments made, economic evaluation studies that can demonstrate objective value in multiple ways (e.g., monetary outcomes, measures of gains in quality of life, reductions in years of potential life lost, reductions in potentially preventable hospitalizations) are recommended. such studies are important to inform local, state, and national stakeholders about the potential return on investment for these and similar studies and should complement other evaluation activities of similar initiatives to reach a broader audience. while there were many strengths in this community-based study, there were some limitations that must be acknowledged. this is a case study of a single diabetes education program in a geographic area. hence, the findings, while promising, may not be generalizable to all community diabetes prevention and control programs or to other areas with differing population characteristics, settings, or varying levels of baseline risk (e.g., a c level). additionally, in contrast to academic-based research studies, service delivery often has priority in community-driven programs relative to data collection and management processes, which can limit the types and quality of data collected. for example, although there was a record of engagement by partnering organizations, there was no record of the extent to which organizations agreed to participate when asked. furthermore, while a large sample size was used, lack of randomization in community settings could be impacted by selection bias. the re-aim model provided a general framework for reporting the planning and evaluation of this initiative. as such, full measures on all re-aim dimensions were not collected. while this is a potential shortcoming, it is also aligned with the recognition that applying the re-aim model in "real-world" studies does not depend on the assessment of all five dimensions [ ] . despite the relatively large numbers of community residents served by the diabetes education program, the proportion reached relative to people with diabetes residing in these south texas counties was still minimal, given the high rates of adults with diabetes in the south texas region [ ] . further, the large attrition rate for follow-up sessions was considerable, which may highlight recruitment or fidelity issues and introduce self-selection and/or a healthful bias (i.e., participants with type diabetes with lower a c levels had better retention rates at all follow-up sessions). finally, data were not collected longer than months following the diabetes education program workshop; therefore, an assessment of long-term clinical control and management among participants was not possible. similarly, as the healthy south texas initiative is still ongoing, long-term program delivery and institutionalization post external funding could not be assessed. however, lessons can be learned from this initiative that advance knowledge about research translation. in line with guidelines for implementing evidence-based diabetes prevention and control programs [ ] , two successful strategies were employed to enhance reach with the ultimate goal of reducing health disparities in underserved populations. first, community health workers were integral to participant recruitment because they were seen as trusted members in the community [ ] . another successful strategy was establishing and using diabetes health champions [ ] (i.e., persons in the program who had successfully lowered their own a c levels) to serve as program promoters who could engage populations typically characterized as "hard to reach" and who were unaware of, or previously uninterested in, participating in health promotion programs [ ] . the diabetes education program provided an example of dedicated effort to meet the overall public health goal of diabetes prevention and management for all americans, especially among those experiencing a multitude of social determinants of health inequities [ ] . offering the diabetes education program through two regional hubs was a major advantage for program reach and adoption as well as launching the initiative quickly. overall, the diabetes education program, as part of the healthy south texas initiative, made a substantial impact on the target area reaching diverse and potentially at-risk populations with measured benefits as evidenced in the current study. for long-term programmatic sustainability, such programs will need to be viewed as essential to routine diabetes regional risk: mapping single and multiple chronic conditions in the united states regional differences in rural and urban mortality trends; nc rural health research program: chapel hill trends in socioeconomic status-related differences in mortality among people with chronic obstructive pulmonary disease understanding associations among race, socioeconomic status, and health: patterns and prospects healthy border : a prevention & health promotion initiative emergent public health issues in the us-mexico border region; frontiers in public health centers for diabetes control and prevention. diagnosed diabetes 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creative commons attribution (cc by) license the authors would like to thank the healthy south texas team within the texas a&m health science center for their work to deliver and evaluate this program. a special thanks is given to the diabetes education program trainers, educators, and staff in corpus christi and mcallen who are continually dedicated to improving lives in south texas. additionally, the authors would like to thank carrie l. byington, former senior vice president of the texas a&m university health science center and vice chancellor for health services of the texas a&m university system (currently executive vice president and head of uc health at the university of california) and susan ballabina, deputy vice chancellor for texas a&m agrilife for their leadership role in the healthy south texas initiative during the study period. the authors declare no conflict of interest. key: cord- -wlzgq f authors: yan, alice f.; sun, xiaomin; zheng, jinge; mi, baibing; zuo, hui; ruan, guorui; hussain, akhtar; wang, youfa; shi, zumin title: perceived risk, behavior changes and health-related outcomes during covid- pandemic: findings among adults with and without diabetes in china date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: wlzgq f aims: to examine perceived infection risk of covid- and the health and related behavior changes among people with diabetes, compared with people without diabetes, and to examine factors associated with self-reported health during the national quarantine period in china. methods: the china covid- survey is an anonymous -item survey administered via social media across china. a national sample of , adults in all provinces in mainland china provided data on sociodemographic characteristics, awareness, attitudes towards covid- , lifestyle factors, and health outcomes during the quarantine. regression models tested associations among study variables adjusting for covariates. results: among the , total participants ( . % men and . % women), reported having diagnosed diabetes and , had no diabetes. participants with diabetes perceived themselves to be at higher risk and were more worried about being infected with covid- when compared to non-diabetic individuals (p<. ). during the covid- pandemic, participants with diabetes were more likely to experience food and drug shortages and to increase their physical activity, compared to their counterparts. among diabetic respondents, a high proportion of current smokers ( . %) and drinkers ( . %) reported increased amounts of smoking and drinking. people with diabetes were % less likely to report excellent or very good health. having minutes/week physical activity was positively associated with excellent or very good health (prevalence ratio, pr= . , %ci . - . ). conclusions: a high proportion of people with diabetes perceived risk of covid- infection and increased their smoking and drinking during the pandemic. since the outbreak of the novel coronavirus disease (covid- ) was first reported in wuhan city in china in december [ ] , it has quickly become a global pandemic. a novel betacoronavirus, known as the severe acute respiratory syndrome coronavirus (sars-cov- ), was identified as the pathogen for covid- [ ] . china implemented a lockdown of wuhan in late january to contain the spread of covid- . on march , , the world health organization (who) declared covid- , which triggered severe pneumonia and acute, even lethal, lung failure, a pandemic [ ] . covid- infection is a double challenge for people with diabetes. it was reported that among covid- patients admitted to hospitals, diabetes was the second most prevalent comorbidity (with a rate of approximately - %) [ ] [ ] [ ] . a growing body of clinical and population studies shows that patients with diabetes, when contracting sars-cov- , are more likely to develop severe symptoms and complications [ , ] , and they have much higher admission rates in intensive care units. the risk of dying from covid- was up to % higher for those with diabetes, particularly among elderly type diabetes cases [ ] than for people without diabetes [ , ] . in addition to the direct vulnerability to the worst outcomes of covid- , people with diabetes can be affected by limited access to healthcare due to massive population lockdowns. consequently, their health condition would become worse. second, the prolonged period of quarantine and social distancing, although effective to contain the spread of the virus, is likely to have undesirable effects on the lifestyle behaviors and health and well-being of chronic disease patients, including those with diabetes. third, during pandemics such as covid- , vulnerable populations, including women, the elderly, and those with chronic diseases, become more vulnerable due to their impaired ability to access and understand health information and make sound, informed decisions. china has the largest number of diabetes patients in the world, and the number has been continually rising due to the improvement of living standards and increase of obesity. china has an estimated million adults living with diabetes ( . % total diabetes and . % prediabetes) [ ] [ ] [ ] . so far, it is unknown how chinese diabetes patients perceived covid- related risks and how they modified their health-related behaviors accordingly during the pandemic. the objectives of this time-sensitive study are: ) to examine perceived risk of covid- and levels of worry among people with diabetes, and compare with the perceptions of those without diabetes; ) to examine the health-related experiences and behaviors of people with diabetes when compared with those without diabetes, and ) to examine factors associated with self-reported health status during the covid- quarantine period in china. the china covid- survey is a cross-sectional anonymous survey that was administered via wechat, china's leading social network. almost every chinese adult uses wechat daily, and many children use it as well. we selected this platform not only because the nation was under quarantine and we could only reach respondents online, but also because wechat is china's leading social network with more than one billion users, and most chinese adults use wechat daily. based on national usage statistics in , the wechat's penetration rate in china is % among - -year-olds. [ ] survey data collection was administered between april and early may , . we used both snowball and convenience sampling approaches to recruit a diverse sample in china. the china covid- survey questionnaire has items and provides about study variables. it covers comprehensive topics: ) awareness, knowledge, attitudes, and practices toward covid- , ) personal experiences and impacts of covid- , ) attitude toward government responses to covid- , ) healthcare-seeking behaviors, ) demographics characteristics, ) lifestyle behaviors, ) psychological well-being , and ) health outcomes, including obesity and other non-communicable diseases (ncds) during the covid- pandemic. the xian jiaotong university institutional review board approved study procedures, and participants provided consent online. data includes a national sample of , adults aged>= years in province-level administrative units. for the present study, the study sample included , participants. of the total, , have neither diabetes nor other ncds (hypertension, heart disease, stroke, cancer, asthma, chronic lung disease, etc.) (n= , ; referred to as "people without diabetes" hereafter) and people have been diagnosed as having diabetes (n= ; referred to as "people with diabetes" hereafter). those with other ncds but not diabetes were excluded in the analysis. we focused on the following study variables: demographic characteristics, awareness and attitudes toward covid- , lifestyle behaviors, sleep, and quality of life. data on demographic characteristics, including gender, education, income, residence, and occupation were collected and then included as covariates in analysis models. for this study, we awareness and attitudes towards the covid- were assessed using items adapted from a recent covid- awareness, attitude, and action questionnaire [ ] . two questions asked participants to rate the likelihood they perceived that they or someone in the family might get we adopted the questionnaire developed by conway and colleagues [ ] . two items, drug shortage and food shortage due to covid- , were used to measure coronavirus experiences. measures of health-related behaviors, including changes in lifestyle behaviors (diet, physical activity, and sleeping), were assessed using items from the kadoorie study of chronic disease in china (kscdc) [ ] and the ccdrf survey [ ] . these surveys were validated in the chinese population. body mass index (bmi) was calculated using self-reported weight and height. we used bmi>= to define overweight/obese [ ] . physical activity during covid- was measured with items adapted from the international physical activity questionnaire (ipaq) [ ] . we then calculated participants' weekly physical activity minutes and whether they meet the min weekly physical activity recommendation. participants' self-rated health [ ] was measured by the most commonly used item from patient-reported outcomes measurement information system (promis) item with responses from poor to excellent. to assess chronic disease status, participants completed questions regarding the following questions: "did they currently have a chronic disease? if so, they were to identify specific diseases or health conditions." healthy individuals who self-identified of having no existing chronic diseases were defined as "healthy people without diabetes," those who self-identified as having diabetes was defined as "people with diabetes." those with other chronic diseases but no diabetes was excluded in the analysis. we first described the distribution of sample characteristics including age, gender, education, income (low, medium, high based on tertiles), residence (city, town, and rural), smoking (non-smoker, current smoker, ex-smoker), and alcohol drinking (non-drinker, current drinker, ex-drinker), body mass index (bmi, based on reported weight and height), and weight status (classified based on bmi>= for overweight and >= for obesity, which are the chinese national bmi cut points), and analysed these by the subjects' diabetes status. chi square test was used to compare differences between groups for categorical variables and anova for continuous variables. second, we graphically presented the distributions of frequency of physical activity, change in smoking and alcohol drinking by perceived covid- infection risk with bar charts. then we performed a multivariable poisson regression with robust variance to calculate prevalence ratio (pr) [ ] , to assess the association between diabetes status and lifestyle behaviour changes during covid- pandemic with self-reported health (excellent/very good vs. others), while controlling for sociodemographic variables. it is usually preferable to use prs instead of odds ratios (ors) in cross-sectional studies when the prevalence of outcome measures is above % [ ] . all the analyses were performed using stata . (stata corporation, college station, tx, usa). statistical significance was considered when p< . (two-sided). the sample characteristics by diabetes status are summarized in table . a total of , participants ( , men and , women) were included in the present study, of which ( . %) reported having diabetes. compared to participants without diabetes, more participants with diabetes were men ( . %) and older. they were more likely to live in cities ( . %), had a lower level of education, a high level of income ( . %), and were overweight ( . %) or obese ( %). notably, those with diabetes were more likely to be current smokers ( . % vs. . %, p< . ) and current alcohol drinkers ( . % vs. . %, p< . ), compared to those without diabetes. the prevalence of daily exercise was . % in participants with diabetes vs. . % in participants without diabetes (figure ) . when asked about participating in certain types of exercise, people with diabetes (when participated in physical activity) were more likely to do tai chi and/or qigong than the others ( . % vs . %). perceived high covid- infection risk was associated with increases in smoking and drinking (figure ) . among those who perceived high infection risk, . % of the smokers increased smoking a lot and . % drinkers increased drinking a lot. the corresponding figures were only . % and . % among those individuals that did not perceive themselves to be at a higher risk of infection. findings (table ) from the multivariable poisson regression model showed associations between diabetes and lifestyle behavior changes during covid- pandemic with self-reported health, controlling for demographic characteristic. the model showed that those with diabetes were % less likely to report having excellent/very good health. obtaining minutes/week physical activity was positively associated with excellent/very good health (pr . , %ci . - . ). compared with those who reported no change of pa, those individuals who increased pa levels were more likely to report excellent/very good health. compared with those who obtained - hours of sleep per day, participants who got less than hours of sleep were % less likely to report excellent/very good health. changes in drinking were not associated with self-reported health outcomes. surprisingly, those who reported increases in smoking were more likely to have excellent/good health. risk factor assessments based on pandemic data from multiple countries, although still notably limited [ ] [ ] [ ] [ ] [ ] ] , indicate that those at higher risk for severe illness from covid- include older males, and people with obesity and related comorbidities such type diabetes. as china has the highest number of obese and diabetic patients worldwide (about % of adults are obese or overweight) [ , ] , and million adults living with diabetes ( . % total diabetes and . % prediabetes [ ] ), it is critical to understand how covid- impacts chinese adults, especially those with chronic conditions like diabetes and overweight/obesity, which likely coexist. to our knowledge, this study is the first sizeable nationwide survey to examine chinese diabetics and healthy non-diabetic residents' attitudes towards covid- risks and the impact of covid- on health-related behavior changes, and self-related health during the home quarantine period in china. the survey respondents were from all the provinces, municipal cities, and special administrative regions of china. our study shows that chinese adults with diabetes were more likely to perceive a high risk of covid- infection and high level of worry than those without diabetes. literature has shown that food insecurity is an important risk factor for type diabetes. [ ] people with diabetes are more dependent on the regularity of food and medicine and therefore this may have caused the perceived risk of food and drug shortage. concurrently, a higher proportion of individuals with diabetes reported an increase in smoking and drinking than those without diabetes in our sample. we attempted to investigate the association between self-reported health and the alcohol drinking and smoking. we found that those who increased smoking were more likely to have excellent/good health. although this cross-section data does not allow us to draw a causal conclusion, we propose two explanations for future studies to validate. first, increased alcohol consumption and smoking may be related to elevated anxiety and stress due to prolonged isolation and uncertainly during the covid- pandemic. when people's lives are stressful, alcohol consumption and tobacco smoking may become a coping approach for their stress. second, the controversial, unproven but popular social media claims that [ ] tobacco or nicotine could reduce the risks of covid- may play a role in shaping at-risk individuals' behaviors. with around million adult smokers, and accounts for nearly one-third ( %) of smokers worldwide in china [ ] , the use of tobacco products is of particular concern during the covid- pandemic. we advocate for more research to examine the role of smoking in the contraction, transmission, and mortality rate of covid- . previous research suggest that alcohol consumption is a potential risk factor for type diabetes [ , ] . regardless of the amount of alcohol a person consumes, alcohol consumption can weaken the immune systems [ ] . people with problematic drinking behaviors can be among the most vulnerable populations for covid- infection [ ] . given the high rates of smoking and drinking among those with diabetes, countries should allocate resources to health stimulus packages, scientific research, and health promotion campaigns to further reduce alcohol drinking and smoking rates. the covid- pandemic casts new light on some old problems: medication access, drug shortages, and food shortages. our findings showed that diabetic patients were at higher risk for drug and food shortages. although some global supply disruptions and shortages cannot be predicted or prevented, government agencies and healthcare providers can provide telemedicine, mail order pharmacy, home delivery, and drive-thru or curbside pick-up of groceries or medications in order to mitigate the shortages while enhancing social distancing. while china is slowly beginning to reopen since lifting the lockdown in mid-may, it is of interest to understand how people coped with stress during the time of social distancing and home quarantine in china. our findings indicate that having an adequate amount of physical activity (i.e., engaging in weekly physical activity for minutes or more) and increasing physical activity during pandemic were positively associated with self-reported excellent/very good health. insufficient sleep was more common in people with diabetes than people without diabetes and was related to poor health. these findings further highlight the importance of the promotion of health and wellness during covid- . this study has some strengths and limitations. to our knowledge, no studies to date have reported findings related to perceived infection risks and the impacts of covid- on a large sample of people with diabetes on health-related outcomes and lifestyle behavior changes in china, where covid- was first reported, and many vigorous nationwide measures were taken to control its spread. our findings may shed light on how to target or manage risk factors (i.e., drinking and smoking) for the diabetic population during the pandemic. given the anonymous design of the online survey, such an approach can work better to collect people's honest answers, especially about sensitive information; and it is more feasible in special situations like covid- , where face-to-face interviews are difficult. this study has some limitations. first, potential self-selection bias is common in survey data, including ours due to the use of convenience and snowball sampling method. our sample may also have bias related to age or education since . % of diabetic adults have a bachelor's degree in comparison to % of non-diabetic adults. however, some health indicator rates from our data, such as rates of overweight/obesity and diabetes, were consistent with those from other national survey data [ , ] . second, the sample was relatively young ( . % of participants were - years old and . % years old and above). therefore, the observations are limited and cannot be extrapolated to older individuals who likely have different perceptions of the covid- pandemic. third, the survey questionnaire did not ask participants to identify the specific type of diabetes that they had been diagnosed. although we did not attempt to distinguish type diabetes from type by self-report, the vast majority of diabetes cases in china are currently type [ ] . fourth, the self-reporting scale used for changes in smoking and drinking was crude and subjective (changed a lot, change a little, et al). we did not collect the baseline data for tobacco or alcohol consumptions prior to covid- and cannot really quantify the changes. in addition to collecting data on the self-reported changes in smoking and alcohol consumption for the current diabetic smokers or drinkers during covid- as this study did, it is also important to know the prevalence of initiation of smoking/drinking during the covid- pandemic. fifth, the number and/or types of medications taken as well as duration of diabetes were not collected in the survey. this was because stratified analysis by number of medications taken by participants would require a much larger sample size. this was beyond the scope of the current investigation. lastly, a review by dryhurst and colleagues [ ] pointed out that many rapid-response studies almost exclusively rely on single-item measures of risk perception, selectively tapping into either cognitive or emotional dimensions. this study's two-item measures of risk perception share the above-mentioned limitation. risk perception is a subjective psychological construct that is influenced by cognitive, emotional, social, cultural, and individual variation both between individuals and between different countries [ ] . we encourage future studies to include theory-based measures of risk perception that involve multidimension determinants of risk perception. in conclusion, our results showed that chinese adults with diabetes perceived themselves at high risk for covid- infection and were more worried about being infected when compared to individuals without diabetes. they reported experiences with shortages of food and medication and exhibited adverse lifestyle behaviors and declined health. even though we cannot identify precisely what caused the fear, it may be hypothesized that imprecise information and instructions of being at higher risk for covid- and death in people with diabetes by media and government, without necessary follow-up and support structures in place, created the anxiety. this is indeed a wake-up call, a tocsin, to the world on the importance of primary prevention and providing good support to chronic disease patients, including those with diabetes. a novel coronavirus outbreak of global health concern identification of a novel coronavirus in patients with severe acute respiratory syndrome clinical considerations for patients with diabetes in times of covid- epidemic clinical features of patients infected with novel coronavirus in wuhan prevalence of comorbidities and its effects in patients infected with sars-cov- : a systematic review and meta-analysis epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study are patients with hypertension and diabetes mellitus at increased risk for covid- infection? the clinical characteristics and outcomes of diabetes mellitus and secondary hyperglycaemia patients with coronavirus disease : a single-center, retrospective, observational study in wuhan practical recommendations for the management of diabetes in patients with covid- clinical characteristics and outcomes of patients with severe covid- with diabetes american diabetes association. how covid- impacts people with diabetes prevalence and ethnic pattern of diabetes and prediabetes in china in diabetes in china: epidemiology and genetic risk factors and their clinical utility in personalized medication global and regional diabetes prevalence estimates for and projections for and : results from the international diabetes federation diabetes atlas wechat revenue and usage statistics business of apps disease and disparity in china: a view from stroke and mi disease attitudes, and actions related to covid- among adults with chronic conditions at the onset of the u.s. outbreak social psychological measurements of covid- : coronavirus perceived threat, government response, impacts, and experiences questionnaires. national institute of health cohort profile: the kadoorie study of chronic disease in china (kscdc) predictive values of body mass index and waist circumference to risk factors of related diseases in chinese adult population validity of the international physical activity questionnaire short form (ipaq-sf): a systematic review general population estimate for "excellent" to "poor" self-rated health item alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio a comparison of two methods for estimating prevalence ratios obesity as a predictor for a poor prognosis of covid- : a systematic review new national data show alarming increase in obesity and noncommunicable chronic diseases in china prevention and control of obesity in china food insecurity is an important risk factor for type diabetes: a case-control study of new referrals to the university clinics two important controversial risk factors in sars-cov- infection: obesity and smoking tobacco and the lung cancer epidemic in china alcohol and type diabetes. a review. nutrition, metabolism and cardiovascular diseases alcohol consumption and risk of pre-diabetes and type diabetes development in a swedish population alcohol and the immune system covid- hangover: a rising tide of alcohol use disorder and alcohol-associated liver disease understanding the china blue paper on obesity prevention and control and policy implications and recommendations for obesity prevention and control in china diabetes in china: epidemiology and genetic risk factors and their clinical utility in personalized medication risk perceptions of covid- around the world the authors would like to thank the study participants, collaborators, and staff members who contributed to this study. in particular, we would like to thank professors shiyong liu, peng ni and qianli xue, and mrs. lihua yan.author contributions: a.f.y, y.w, z.s. contributed to the study design, data collection, and drafting the report. all authors contributed to interpretation of the data, commented on and revised the report, and approved the final version for publication. board (grant number: - ) and xi'an jiaotong university global health institute. key: cord- -dftdxzsm authors: rayman, g.; lumb, a.n.; kennon, b.; cottrell, c.; nagi, d.; page, e.; voigt, d.; courtney, h.c.; atkins, h.; platts, j.; higgins, k.; dhatariya, k.; patel, m.; narendran, p.; kar, p.; newland‐jones, p.; stewart, r.; burr, o.; thomas, s. title: dexamethasone therapy in covid‐ patients: implications and guidance for the management of blood glucose in people with and without diabetes date: - - journal: diabet med doi: . /dme. sha: doc_id: cord_uid: dftdxzsm the recovery (randomised evaluation of covid‐ therapy) trial found that dexamethasone mg once per day for days reduced deaths by one‐third in ventilated patients and by one‐fifth in other patients, receiving oxygen therapy. this equates to the prevention of one death in around eight ventilated patients, or one in around patients requiring oxygen. this article is protected by copyright. all rights reserved the recovery (randomised evaluation of covid- therapy) trial found that dexamethasone mg once per day for days reduced deaths by one-third in ventilated patients and by one-fifth in other patients, receiving oxygen therapy [ ] . this equates to the prevention of one death in around eight ventilated patients, or one in around patients requiring oxygen. this welcome news has been considered such an important therapeutic advance that the regimen has been fast-tracked in the uk even though the study has yet to attain peer review publication. although described by the investigators as 'low dose dexamethasone therapy' the dose is in effect five-to six fold greater than the therapeutic glucocorticoid replacement dose. high doses of glucocorticoids exacerbate hyperglycaemia in people with diabetes, may unmask undiagnosed diabetes and, in those at risk of diabetes, may precipitate hyperglycaemia and new-onset diabetes (commonly termed 'steroid-induced diabetes'). furthermore, glucocorticoids are the commonest cause of people with diabetes developing potentially life-threating hyperglycaemic hyperosmolar state (hhs) in hospital. to prevent these harms, the joint british diabetes societies (jbds) published guidelines on the management of inpatients with and without diabetes receiving steroid therapy [ ] . however, these guidelines, which have been adopted in most uk hospitals, may not be appropriate for those with severe covid- infection receiving dexamethasone, given the additional impact of the disease on glucose metabolism. the 'cytokine storm' resulting from severe covid- infection is associated with significant insulin resistance and reduced insulin production from the pancreatic  cells. this dual pathology can precipitate severe hyperglycaemia, life-threatening ketoacidosis and hhs in people with diabetes, and even in people without, diabetes [ ] . to prevent these harms, the uk national diabetes covid- response group published in this journal guidance on the management of covid- -related hyperglycaemia [ ]. however, given the 'triple insult' of dexamethasone-induced impaired glucose metabolism, covid- -induced insulin resistance and covid- impaired insulin production, we now provide new guidance specifically for use in people with severe covid- infection commencing dexamethasone. the aim is to ensure that all patients commenced on dexamethasone, whether or not they have diabetes, receive appropriate glucose surveillance and management of hyperglycaemia should it occur. the guidance informs the clinician of the key facts pertaining to this clinical situation and the reasons why these recommendations differ from the jbds guidelines. it describes the frequency at which capillary blood glucose monitoring should be this article is protected by copyright. all rights reserved undertaken in those with and without diabetes and gives the target ranges of capillary blood glucose levels to aim for. the guidance recommends giving correction doses of rapid-acting analogue insulin when capillary blood glucose > . mmol/l, with the dose calculated according to the patient's weight or in those already treated with insulin, on their total daily insulin dose. the correction doses recommended are notably higher than those used in our previous hyperglycaemia guideline given the inevitable increase in insulin resistance. unlike the previous guidance, we do not recommend using the insulin correction ratios that some people with type diabetes usually use as these may not be appropriate given the significant disturbance of glucose metabolism. to maintain glycaemic control we recommend using nph insulin which has an intermediate duration of action in preference to longer-acting insulin even though the metabolic effects of dexamethasone can persist for up to h. nph insulin given twice daily allows more flexibility in dose adjustment. the starting doses based on weight are slightly greater than those given in our previous guidance but as before, a reduced dose should be used in the frail, elderly and those with an egfr of < ml/min. if the patient is already on a long-acting insulin or twice daily pre-mix insulin then it is recommended this be increased by %, but it is noted that this may actually require rapid escalation by % or more [ ] . insulin resistance will fall when dexamethasone is stopped and so capillary blood glucose and insulin dose adjustment need careful monitoring to avoid hypoglycaemia. the guidance table for the nph and long-acting insulin assists in dose escalation and down titration of these insulins. finally, close initial follow-up is advised for those with known diabetes and a yearly hba c measurement is recommended for those with steroid-induced hyperglycaemia because this group have been shown to be at increased risk of developing diabetes at a later date. we hope that these guidelines will be helpful for those managing patients with covid- treated with dexamethasone in the ward setting. although not intended for critical care units where policies around blood glucose monitoring may differ and where insulin is likely to be given by intravenous infusion, the guidelines may be adapted for use in this setting. concise advice on inpatient diabetes (covid:diabetes): › dexamethasone reduces mortality in people with covid- who require ventilation or oxygen therapy › corticosteroid therapy impairs glucose metabolism and is the commonest cause of life threatening inpatient hyperglycaemic hyperosmolar syndrome (hhs) › covid- increases insulin resistance and impairs insulin production from the pancreatic beta cells; this can precipitate hyperglycaemia and life threating diabetic ketoacidosis (dka) in people with diabetes and even in people not known to have diabetes › glucose levels above . mmol/l have been linked to increased mortality in people with covid- › the recommended dexamethasone dose of mg/day (oral or iv) for days, equivalent to mg of prednisolone/day, will undoubtedly afect glucose metabolism › thus, the triple whammy of dexamethasone induced impaired glucose metabolism, covid- induced insulin resistance and covid- related impaired insulin production could result in signiicant hyperglycaemia, hhs and dka in people with and without diabetes, increasing both morbidity and mortality › sulphonylureas are not recommended in this context as beta cell function may be impaired and insulin resistance is likely to be severe. for this reason, these recommendations difer from those in the jbds guideline on the management of hyperglycaemia and steroid (glucocorticoid) therapy q to ensure all patients on dexamethasone receive appropriate glucose surveillance and appropriate management of hyperglycaemia target glucose . - . mmol/l (up to . mmol/l is acceptable) check the glucose at least hourly ideally at fasting periods (e.g. before meals and at bedtime). if after hours all fasting glucose results are < . mmol/l reduce frequency to once daily at . - . hrs. continue until dexamethasone is stopped if any fasting glucose is above . mmol/l continue hourly monitoring and follow the guidance below to correct hyperglycaemia i.e. glucose above . mmol/l throughout the admission, check fasting glucose at least hourly, or more frequently if the glucose is outside the . - . mmol/l range q this guidance is for use in all patients with covid- who are treated with dexamethasone in a ward setting use subcutaneous rapid acting insulin analogue (novorapid®/humalog®/apridra®) as described below. note these are conservative doses and depending on response in individual patients, as previously stated, may need to be increased rapidly (or where more insulin sensitive, decreased) recheck glucose at hrs to determine response and whether a further correction dose is needed follow the weight-based tables below in those people: » not known to have diabetes » with type diabetes treated with diet alone or with oral hypoglycaemic agents where the total daily dose (tdd) of insulin is known follow the guidance in the increase the long acting basal or nph insulin by % but this may need rapid escalation by as much as % depending on response. titrate the dose using the tables below. patients on basal-bolus regimens may not require 'mealtime' insulin boluses if not eating, however, if hyperglycaemia persists during adjustment of basal insulin then use corrective rapid acting insulin doses according to total daily insulin dose (tdd) or weight given in the table for correction doses of rapid acting insulin leicester diabetes centre › people on twice-daily pre-mix insulin e.g. novomix ®/humulin m ®/humalog mix ®/humalog mix ® consider increasing the morning dose by % but this may need rapid escalation by as much as % each day depending on the response doses can be titrated daily, although longer-acting insulins may take - hours to reach steady state. dose adjustments will afect blood glucose throughout the day if the person is too unwell to manage their pump, transfer to a variable rate intravenous insulin infusion (vriii) with a basal insulin given alongside -seek the advice of the diabetes team. if the pump is removed, give the pump to a relative for safekeeping or label with the patients details and safely store those people well enough to manage their subcutaneous insulin infusion pump should be recommended to initially increase the basal rates by % and be made aware that this may need to be increased further on a daily basis. refer all people using a personal insulin pump to the diabetes team insulin resistance will begin to fall when the dexamethasone has been stopped but may take a number of days. continue to monitor glucose hourly and down titrate using the guidance table above normoglycaemia may be established after stopping dexamethasone without the need for ongoing diabetes therapy. however, up to a third of people may later develop diabetes therefore alert the gp that the patient will need a yearly hba c measurement › people with known diabetesthese patients will require close support following discharge. the discharge guidelines and patient information lealet produced by this group are available to facilitate this. the lealet can be accessed here: https://www.diabetes.org.uk/professionals/resources/shared-practice/inpatient-and-hospital-care#patients key: cord- - b btzrx authors: liu, zhelong; bai, xi; han, xia; jiang, wangyan; qiu, lin; chen, shi; yu, xuefeng title: the association of diabetes and the prognosis of covid- patients: a retrospective study date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: b btzrx abstract aims this study evaluated the impact of previous glycemic control and in-hospital use of antidiabetic/antihypertensive drugs on the prognosis of covid- patients with diabetes. methods in this retrospective cohort study, consecutive inpatients with laboratory confirmed covid- were enrolled from tongji hospital (wuhan, china). patients without diabetes were matched to those with diabetes based on age, sex, and comorbidities. all patients were followed up to a clinical endpoint (discharge, worsening including transferring to icu or immediate death). data and outcomes were extracted from medical records and analyzed. results patients with pre-existing diabetes were included in this study, with matched patients without diabetes included as a control group. patients with diabetes had a higher rate of worsening ( . % versus . %, p= . ). multivariable regression showed increased odds of worsening associated with previous glycemic control reflected by hba c (odds ratio . , % ci . - . , p= . ) and receiver-operating characteristics (roc) curve identified hba c of . % ( mmol/mol) as the optimal cut-off value. univariate analysis demonstrated the in-hospital use of antidiabetic/antihypertensive drugs were not associated with a higher risk of worsening. conclusions covid- patients with diabetes had a higher risk of worsening, especially those with poorly-controlled hba c, with an optimal cut-off value of . %. the in-hospital use of antidiabetic/antihypertensive drugs were not associated with increased odds of worsening in patients with diabetes. since dec , the novel coronavirus disease has spread rapidly around the world and infected more than million people hitherto [ ] . the pathogen was identified as a novel, highly contagious severe acute respiratory syndrome coronavirus (sars-cov- ), which can invade the human body through angiotensinconverting enzyme (ace- ) [ ] . the clinical manifestations of covid- include fever, dry cough, dyspnea, myalgia, fatigue etc, and severe cases can rapidly develop into acute respiratory distress syndrome, septic shock, and multiple organ dysfunction syndrome [ ] . recent studies have shown that diabetes mellitus (dm) is one of the most common comorbidities of covid- , with a prevalence ranging from . % to . % [ ] [ ] [ ] . diabetes has been associated with an increased mortality in previous viral epidemics, such as the outbreak of sars-cov- and middle east respiratory syndrome coronavirus [ , ] . similar conclusions were reported in the pandemic of sars-cov- . some studies have suggested that diabetes is a risk factor for the poor prognosis of covid- [ , , ] , while some studies reported that patients with diabetes seemed not to have a higher mortality risk [ , ] . data regarding the impact of diabetes on the prognosis of covid- patients are scant and controversial. good glycemic control should be the most important for patients with diabetes during the covid- infection as it has been shown to improve the innate immune system [ , ] . data from other viral epidemics such as sars and influenza h n has demonstrated that patients with poor glycemic control have a higher mortality risk [ , ] . unfortunately, the previous studies mostly focused on the impact of diabetes, as a comorbidity, on the prognosis of covid- . despite a few studies reported that covid- patients with poorly controlled fasting blood glucose in hospital were associated with higher mortality [ ] , there is still a lack of information on the impact of previous glycemic control on the prognosis of covid- patients with diabetes. in addition, previous studies have reported that metformin could increase ace- expression and improve its stability by impeding its ubiquitination and proteasomal degradation [ ] . angiotensin-converting enzyme inhibitors (acei) and angiotensin ii receptor blockers (arb) also have been considered as a link between covid- and diabetes because they are widely used in patients with diabetes [ ] . however, there are still no solid evidences demonstrating the impact of these medications on the prognosis of this population. in this report, we aimed to evaluate the prognosis of covid- patients with diabetes and the impact of previous glycemic control on it. besides, the influence of the commonly used antidiabetic and antihypertensive drugs on the prognosis of patients with diabetes was also explored. [ ] . patients with diabetes were designated according to the patient's medical history. then the patients without diabetes were matched ( : ratio) to the patients with diabetes based on age, sex, and comorbidities (hypertension, hyperlipemia, chronic renal diseases). the study was approved by the ethics committee of tongji hospital (tj-irb ). written informed consent forms were waived in the urgency of pandemic. a trained team of physicians extracted the epidemiological, demographic, clinical, laboratory, treatment, and prognosis data from electronic medical records. the demographic characteristics, comorbidities, clinical symptoms, symptoms from onset to admission, vital signs, laboratory findings, antidiabetic and antihypertensive drugs used prior to admission and during hospitalization, and outcomes were collected. most of the clinical data used in our study were collected from the first day of admission unless otherwise stated. comorbidities were determined based on the patient's selfreport on admission. the glycated hemoglobin a c (hba c) and the maximum of the blood glucose (bg) in-hospital were used to reflect the previous and in-hospital glycemic control, respectively. all data were double-checked by different researchers to guarantee the accuracy. all patients were followed up to a clinical endpoint (discharge, worsening including transferring to intensive care unit (icu) or immediate death). patients who transferred to icu or died immediately before transferring to icu were classified as the worsening group. continuous and categorical variables were described as median (interquartile range [iqr] ) and number (%), respectively. continuous variables between groups were compared by the mann-whitney u test, and categorical variables were compared by chi-square or fisher's exact test where appropriate. binary logistic regression models were used to evaluate the impact of the previous and in-hospital glycemic control on the outcomes of the patients with diabetes, and three models were constructed to adjust potential confounding factors. model explored the risk factors associated with worsening by a univariate analysis, which included hba c, maximum of the bg in-hospital, age, sex, smoking, comorbidities other than diabetes, white cell count, the percentage of neutrophils, lymphopenia, alanine aminotransferase, aspartate aminotransferase, γ -glutamyl transferase, creatinine, c-reactive protein (crp), d-dimer, n-terminal brain natriuretic peptide precursor (nt-probnp), cardiac troponin i (ctni), prothrombin time, total cholesterol, triglyceride, interleukin- , tumor necrosis factor-α. model included hba c and the maximum of the bg in-hospital for a multivariate logistic regression analysis. on the basis of model , the variables with a p value < . in the univariate analysis were further added for a multivariate analysis in the model . considering the limited number of the patients in the worsening group, three variables, which included lymphocyte, crp and prothrombin time, were added in the model to avoid over-fitting. receiver operating characteristic (roc) curve was used to analyze the predictive value of the hba c level on the prognosis of the patients with diabetes. when we evaluated the association between the use of each antidiabetic or antihypertensive drug and the outcomes, due to the limited number of patients in each subset, logistic regression model was used and only glucose, hba c at admission or maximum of the glucose inhospital were adjusted to avoid over-fitting. the results were shown in odds ratio (or) and % confidence interval (ci). a two-sided p value < . was considered statistically different. all statistical analyses were performed with spss, version . (ibm spss). a total of confirmed covid- patients with pre-existing dm were included in this study (table ) both groups were fever and cough, followed by fatigue and diarrhea ( table ). the patients with diabetes reported a significantly higher incidence of fever ( . % versus . %) compared to the group without diabetes. laboratory findings on admission and clinical outcomes of both groups are summarized in table . the rate of disease worsening during hospitalization was significantly higher in the patients with pre-existing dm compared to the patients without diabetes ( . % complete data collected from patients with diabetes ( in the worsening group, and in the discharge group) were included in the logistic regression models (table ). in the univariable analysis (model ), hba c, maximum of the bg in-hospital, lymphopenia, the percentage of neutrophils, crp and prothrombin time were associated with worsening. in the model included hba c and the maximum of the bg in-hospital, only hba c was associated with increased odds of worsening. when adjusting for lymphopenia, crp and prothrombin time, hba c was still associated with increased odds of worsening. using disease worsening as the end point, roc curve analysis was used to identify the optimal hba c cutoff value, which was . % ( mmol/mol) (figure ). with this value, the area under the roc curve was . ( % ci, . - . , p < . ), and the sensitivity and specificity for predicting disease worsening in the patients with diabetes were . % and . %, respectively. for each laboratory index, patients were divided into groups for further analysis (table ). compared to the hba c well-controlled patients, the poorly-controlled patients presented higher white cell count and the percentage of neutrophils. also, the incidence of lymphopenia was higher in the poorlycontrolled patients. levels of the maximum of the bg in-hospital, hemoglobin, triglyceride, urea nitrogen, prothrombin time and ctni were clearly elevated in the poorly-controlled patients compared with the well-controlled patients. this retrospective cohort study have novel findings with important implications for the covid- patients with diabetes. first of all, not only did we find that covid- patients with pre-existing dm had an increased risk of disease worsening, but poor previous glycemic control, which was reflected by hba c, was associated with higher odds of disease worsening. second, to our knowledge, this was the first study investigating the prognostic value of hba c in the covid- patients with diabetes, and a hba c level of . % ( mmol/mol) was the optimal cutoff value. furthermore, we found that α-glucosidase inhibitors and ccbs use were associated with reduced odds of disease worsening. metformin, insulin, aceis/arbs and statins were not previously, the prognosis of covid- patients with pre-existing dm has been reported. the majority of the studies demonstrated that diabetes was an important risk factor for the progression or mortality in covid- [ , , ] , while some reported that covid- patients with diabetes seemed not to have a higher mortality risk [ , ] . a recent meta-analysis involving studies suggested that covid- patients with diabetes had an increased risk of icu admission and mortality [ ] , which was consistent with the results in our study. it is worth noting that the judgement of preexisting diabetes was based on the patient's self-report at admission, which could lead to the underdiagnosis of diabetes in the control group. in fact, the median level of hba c in the control group was . %, which was above the normal upper limit of hba c ( . %). thus, although our results showed an increased risk of disease worsening in covid- patients with diabetes, the risk might still be underestimated. hba c is considered to be a good indicator reflecting long-term glycemia [ ] . previous studies have reported that patients with poor hba c control were more susceptible to infections, such as the infections of chlamydia pneumoniae, hemolytic streptococci groups b, g, klebsiella pneumoniae, mycobacterium tuberculosis, and exhibited worse prognosis compared to the patients with well hba c control [ ] [ ] [ ] [ ] . besides, chronic hyperglycemia was thought to downregulate ace- expression, making cells susceptible to the damage of sars-cov- [ ] . however, to our knowledge, the association between hba c level and the prognosis of covid- patients with diabetes has not been explored. our study found that among covid- patients, those with poor hba c control had a higher risk of disease worsening, with an optimal cut-off value of . % ( mmol/mol), demonstrating the importance of previous glycemic control. furthermore, we compared the clinical characteristics of the hba c well-controlled group with the poorly-controlled group. the hba c poorlycontrolled patients presented a higher incidence of lymphopenia ( . % versus . %) compared to the well-controlled patients. also, the levels of the percentage of neutrophils, prothrombin time and ctni were significantly elevated in the poorlycontrolled group. the changes in these clinical indicators were consistent with those in the covid- severe cases that have been reported previously [ , , ] , suggesting that the higher risk of disease worsening in the poorly-controlled group might be associated with the changes in these clinical indicators in addition to the poor glycemic control. the association between the in-hospital use of common antidiabetic/antihypertensive drugs and the prognosis of the covid- patients with diabetes was also explored in this study for the first time. the results demonstrated that α-glucosidase inhibitors and ccbs use were associated with a lower risk of disease worsening, and no significant associations were observed between the use of metformin, insulin, aceis/arbs, statins and disease worsening after adjusting for glucose, hba c at admission and maximum of the glucose in-hospital. previous studies demonstrated that ace- ser residue could be phosphorylated to improve the stability and increase the expression of ace- in human umbilical vein endothelial cells by the ′-amp-activated protein kinase, which was the molecular effector of the majority of metformin's pharmacological actions [ ] . special considerations were also recommended on the use of metformin due to the lactic acidosis associated with it [ ] . in addition, previous studies reported that aceis/arbs could upregulate the ace- expression, which might facilitate the entry and proliferation of sars-cov- [ , ] . thus, there are concerns about the safety of using aceis/arbs in patients with diabetes. our results demonstrated that there were no significant associations between the use of metformin, insulin, α-glucosidase inhibitors, aceis/arbs, ccbs, statins and increased odds of disease worsening. even the use of α-glucosidase inhibitors and ccbs were significantly associated with decreased odds of disease worsening. although the potential bias of reverse causation cannot be ruled out, our results at least suggested that the use of these drugs were not associated with a higher risk of disease worsening. however, considering the risk of acute metabolic decompensation caused by metformin in covid- patients with severe symptoms as well as the fact that the maximum of the in-hospital bg alone cannot fully reflect the in-hospital glycemic control, the safety of the in-hospital use of metformin needs more studies to explore. there were some limitations of our study. first, the interpretation of our results might be limited by the sample size. second, owing to the retrospective design of the study, the lack of data didn't allow us to analyze the type of dm, disease course and mean inhospital bg. third, due to the lack of mean in-hospital bg resulting from the urgency of pandemic, only the maximum of the in-hospital bg could be used to reflect the inhospital glycemic control, which could reduce the convictive power of the conclusions about the safety of antidiabetic/antihypertensive drugs. in the urgent conditions, medical history was not taken in detail and some laboratory examinations were not performed in all patients. covid- patients with pre-existing dm had an increased risk of disease worsening, especially those with poorly-controlled hba c, with an optimal cut-off value of . % ( mmol/mol). the in-hospital use of common antidiabetic/antihypertensive drugs were not associated with a higher risk of disease worsening in covid- patients with diabetes. ethical approval for this study was granted by the ethics committee of tongji hospital (tj-irb ). written informed consent was waived due to the urgency of pandemic. the dataset used during the current study are available from the corresponding author on reasonable request. none. all authors read and approved the final manuscript. sc and xy designed the study. zl and xh collected data. xb conducted the analysis and wrote the first draft. wj and lq finalized the manuscript. the corresponding authors attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted. table demographics and baseline characteristics of covid- patients abbreviations: acei, angiotensin-converting enzyme inhibitor; arb, angiotensin ii receptor blocker. figure the predictive value of the hba 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endothelium mitigates pulmonary hypertension should anti-diabetic medications be reconsidered amid covid- pandemic? diabetes research and clinical practice new coronavirus pneumonia prevention and control program diabetic patients with covid- infection are at higher risk of icu admission and poor short-term outcome screening for diabetes in indigenous populations using glycated haemoglobin: sensitivity, specificity, post-test likelihood and risk of disease. diabetic medicine : a journal of the chlamydia pneumoniae infection in adolescents with type diabetes mellitus impact of diabetes and poor glycaemic control on risk of bacteraemia with haemolytic streptococci groups a, b, and g impact of glycemic control on capsular polysaccharide biosynthesis and opsonophagocytosis of klebsiella pneumoniae: implications for invasive syndrome in patients with diabetes mellitus the correlation between ct features and glycosylated hemoglobin level in patients with t dm complicated with primary pulmonary tuberculosis. infection and drug resistance practical recommendations for the management of diabetes in patients with covid- . the lancet clinical features and treatment of covid- patients in northeast chongqing angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during covid- pandemic poor previous glycemic control, which was reflected by hba c, was associated with higher odds of disease worsening, which included transferring to icu or immediate death a hba c level of . % ( mmol/mol) was the optimal cutoff value for the prognosis of covid- patients with diabetes the in-hospital use of common antidiabetic/antihypertensive drugs were not associated with a higher risk of disease worsening in covid- patients with diabetes not applicable. key: cord- -s nong authors: milionis, charalampos; milioni, stella olga title: a brief analysis and hypotheses about the risk of covid- for people with type and type diabetes mellitus date: - - journal: j diabetes metab disord doi: . /s - - - sha: doc_id: cord_uid: s nong covid- is an infectious respiratory disease which firstly occurred in wuhan, china and evolved rapidly around the globe. the causative pathogen is a novel coronavirus called sars-cov- with genomic similarities with sars-cov and mers-cov. the disease is transmitted among humans either through direct contact or via droplets from sneeze or cough. most infected persons remain asymptomatic or mildly symptomatic, but some patients may develop severe clinical features, including pneumonia, respiratory failure, sepsis and even death. people of advanced age and/or with underlying diseases (including diabetes mellitus) are at greater risk. the innate and adaptive immune system are responsible for protecting the body against viral infection. nevertheless, it is assumed that sars-cov- interferes with the immune system through immunomodulating mechanisms which intensify its pathogenesis. a delayed or reduced response of the innate immune system is critical for the development of pathogenesis of the virus. people with diabetes are more likely to develop severe symptoms of covid- . the present article speculates that special aspects of the immune dysfunction caused by chronic hyperglycaemia is the main reason for this susceptibility. coronavirus disease (covid- ) is a respiratory infection which is caused by a novel virus belonging to the coronaviridae family [ ] and is officially named sars-cov- (severe acute respiratory syndrome coronavirus ). in humans, coronaviruses primarily target the respiratory system and have also caused outbreaks of respiratory disease in the past, mainly the severe acute respiratory syndrome (sars-cov) in and the middle east respiratory syndrome (mers-cov) in . they are a large family of positivesense single-stranded rna viruses (+ ssrna) with a crownlike appearance under the electron microscope due to the presence of spike glycoproteins on the envelope [ ] . these viruses derive from animal species (bats, rodents, birds) and can cross barriers between species, also infecting humans [ ] . the transmission of sars-cov- among humans occurs mainly through direct contact or droplets spread by coughing or sneezing from an infected individual [ ] . the incubation period in most individuals varies between and days [ ] . on average, each person has the potential to spread the infection to . - . other people [ ] . the majority of infected individuals (about %) remains asymptomatic or with mild symptoms, whilst the remainder suffer from severe or critical clinical features. the most common symptoms of covid- include fever, cough, sore throat, malaise and dyspnoea. in severe cases, patients may develop pneumonia, acute respiratory distress syndrome, respiratory failure, septic shock and multi-organ failure which can lead to death [ ] . the elderly and those with underlying diseases (such as hypertension, cardiovascular diseases, diabetes mellitus and chronic pulmonary diseases) are more at risk of adverse outcomes [ ] . the first cases of covid- were detected in wuhan, the largest metropolitan area in hubei province, china. the spread of the disease evolved quickly to a pandemic. as of june , , the number of covid- infections globally has exceeded million cases in countries/regions causing more than , deaths [ ] . many issues still remain to be determined with regard to the epidemiological evolution of the disease, especially the de-escalation of its prevalence, possible seasonal fluctuations of its incidence and the risk for future widespread reoccurrences. nevertheless, it is already known that the resulting outbreak of covid- has had a detrimental effect on public health, causing numerous deaths and burdening tremendously the health systems worldwide. for this reason, states around the world have been taking measures to restrict the impact of the spread. at the moment, management strategies aim at reducing transmission in the community and supporting patients with severe clinical features. at the same time, researchers have been working intensively towards the establishment of novel diagnostic procedures, effective therapeutic regimens and prevention products. coronaviruses' entry into susceptible cells is a complex process that is mediated through binding of the viral surfaceexposed spike (s) glycoprotein to the host cell receptor. this interaction promotes the fusion of the viral and cellular membranes. sars-related coronaviruses interact directly with angiotensin-converting enzyme (ace ) via the domain b of the s glycoprotein to enter cells [ ] . ace is mainly expressed in type alveolar cells in the lungs [ ] . the first-line defence against viral infection is the production of type i interferons (ifns-α/β) which is an essential part of the innate immune system. in rna viruses, such as the coronaviruses, the viral genome or the intermediates during viral replication are recognised by either endosomal rna receptors or cytosolic rna sensors in all nucleated cells of mammalians. this interaction leads to a downstream signalling cascade and an accompanying translocation of nuclear factors. this process results in expression of ifns-α/β and other pro-inflammatory cytokines. these interferons act to neighbouring cells and via the jak-stat pathway stimulate the expression of antiviral proteins and induce other biological activities such as inhibition of cell proliferation, regulation of apoptosis and immunomodulation [ ] . a successful response of the ifns-α/β-related innate immune system should be able to control viral replication and dispersion in the body at an early stage, at least to an extent. however, it is believed that sars cov- is able to subvert the host response through the action of structural and nonstructural proteins. due to the genomic sequence similarities with sars-cov (and secondarily with mers-cov), it is assumed that sars-cov- interferes with the relevant signalling processes of the host cells through degradation or inhibition of involved cellular molecules. consequently, the delayed or vitiated infs-α/β response compromises the early viral control, leading to escalation of the concentration of inflammatory neutrophils and monocytes and in turn to overproduction of pro-inflammatory cytokines ('cytokine storm') that manifest the lung immunopathology of covid- [ ] . the adaptive immunity response to sars-cov- has not yet been clarified. presumably, antigens from invading pathogens (most probably the surface-exposed spike glycoprotein but perhaps also the membrane protein) are acquired by respiratory dendritic cells which become activated and present the processed antigen to circulating t cells. activated cd + t cells promote the production of virus-specific antibodies by activating t-dependent b cells, whilst cd + t cells are cytotoxic and can kill infected cells. in addition, b cells produce specific antibodies which may neutralise the invading viruses [ ] . if the pathogenesis in sars applies to covid- , the upregulation of pro-inflammatory cytokines during the delayed innate immunity potentiates the occurrence of severe respiratory manifestations, whilst the progression to adaptive immunity is correlated with recovery [ ] . diabetes mellitus is a clinical syndrome of impaired glucose metabolism with inappropriate hyperglycaemia due to absolute or relative deficiency in insulin secretion, resistance to insulin action, or both [ ] . the most common types of diabetes mellitus include type and type diabetes [ ] . although the clinical diagnosis of the type of diabetes is not always straightforward, type and type diabetes are heterogeneous diseases with considerably different pathophysiology. type diabetes is a catabolic disorder in which pancreatic β-cells fail to respond to all insulinogenic stimuli mainly due to immune-mediated and less frequently due to idiopathic destruction. [ , ] . type diabetes is characterised by various degrees of resistance to insulin action and insulin secretory defect and is associated with other metabolic disorders of the muscle tissue, liver, fat cells, gastrointestinal tract, pancreatic α-cells, kidneys, and brain [ ] . the global prevalence of diabetes mellitus has risen dramatically over the past forty years and it is expected to grow further over the next decades. in , it was approximately . % ( million people) and it is estimated to rise around to . % ( million) by and . % ( million) by [ ] . chronic hyperglycaemia is associated with increased susceptibility to pathogens. many common infections are more frequent and severe in individuals with diabetes mellitus, whilst some rare infections (e.g. rhinocerebral mucormycosis, emphysematous infections of the gallbladder and urinary tract, invasive otitis externa) affect almost exclusively the diabetic population [ ] . although the reasons for this vulnerability are not completely defined, it is believed that abnormalities in innate and adaptive immunity, diminished vascularisation, and facilitation of colonisation and growth of a variety of organisms are critical factors [ ] . in case of viral infections, it is assumed that impairments mainly in innate as well as in cell-mediated and humoral immunity could contribute to the increased susceptibility. the existence of diabetes is strongly associated with an increased risk of developing severe covid- in case of infection with sars-cov- [ , ] . however, it is not clear how diabetes mellitus worsens the clinical presentation of covid- . several suggestions can be made. the present article supports that heightened inflammatory processes constitute the main pathophysiologic factor for the severity of covid- among patients with diabetes mellitus, whilst impairments in immune response and diabetic comorbidities contribute to the aggravated pathogenesis. the primary hypothesis is that chronic hyperglycaemia is involved in inflammatory processes which further activate monocytes and promote the synthesis of pro-inflammatory cytokines, thus aggravating inflammation and injury in the lung tissue and worsening clinical condition. in this mechanism, the excess of circulating glucose causes oxidative stress in which free radical o reduces the availability of nitric oxide (no) and activates a series of pro-inflammatory transcription factors leading to inflammation. moreover, hyperglycaemia increases the expression of tumour necrosis factor-alpha (tnf-a) and inteleukin- (il- ) which further exacerbate inflammation [ ] . a higher propensity to infections due to the involvement of inflammatory processes was documented in studies involving other viruses [ ] . in type diabetes, autoimmunity induces an inflammatory activity which leads to pancreatic β-cell damage. the resultant chronic hyperglycaemia causes oxidative stress, increases the secretion of tnf-α and il- and impairs no-mediated vasodilatation [ ] . in type diabetes, inflammation is also caused by systemic factors, mainly obesity and subsequently insulin resistance. adipose tissue enhances the inflammation process through the action of activated macrophages and the production of proinflammatory cytokines (including tnf-a and il- ) [ , ] . yet it remains unclear whether the innate immune response is vitally impaired in both types of diabetes mellitus and whether hyperglycaemia favours the initial virulence of sars-cov- . diabetes is a chronic condition that can affect the body's immune response to pathogens [ ] . indeed, the proliferative response of lymphocytes is impaired in patients with diabetes, particularly among those with poor glycaemic control [ ] , and low lymphocyte count is a predictor of severe prognosis in patients with covid- [ ] . with regard to the production of neutralising antibodies, it is possible that glycosylation may impair humoral immunity, especially in patients with high hba c values [ ] . furthermore, patients with diabetes mellitus may present dysfunctional type iv (delayed) hypersensitivity reaction and abnormal complement activation [ ] which may hinder the immune response. apart from the defects in inflammatory and immune functions due to hyperglycaemia, complications of diabetes mellitus and treatment regimens may be involved in the vulnerability of these patients. endothelial dysfunction, in particular, may enable sasr-cov- to have an easier access to host cells [ ] . in addition, associated diabetic comorbidities and/ or complications, such as hypertension, cardiovascular disease, and chronic kidney disease may act synergistically and further worsen the prognosis [ ] . especially persons, who are treated with ace inhibitors or angiotensin receptor blockers, have increased expression of ace which could potentially facilitate the infection with sars-cov- [ ] . covid- has evolved to a public health crisis. currently, there is a lack of specific treatments, and only general preventive strategies are available. within this context, appropriate guidance of patients with diabetes should be a priority. social distancing and practicing good hygiene are invaluable tools for diminishing the transmission of sars-cov- . in case of extended periods of isolation, individuals with diabetes should secure access to medications and consumable supplies, such as insulin, glucose test strips, disinfectants, and ensure unimpeded communication with health care professionals, including the use of phone and video calls to minimise face-to-face contact [ ] . although individuals with diabetes do not appear to contract sars-cov- at an increased rate compared to the general population [ ] , poor control of diabetes is associated with a higher risk for adverse clinical outcomes. therefore, it is important that persons with diabetes mellitus maintain an optimal glycaemic control during a sars-cov- outbreak. regular monitoring of blood glucose levels (and urinary ketones when needed) and adherence to treatment are necessary for this purpose. attention to proper nutrition and physical activity (such as indoor exercise and unescorted walking) are also important [ ] . the health crisis due to the covid- pandemic has been a global challenge for states, care systems and individuals. sars-cov- has been exceptionally infectious and pathogenic for humans. patients with diabetes mellitus need to be in the core of health care attention because of greater risk for severe clinical course and mortality. in addition, the global community should focus on the discovery and production of the medical means that will affectively protect populations. identification of a novel coronavirus causing severe pneumonia in human: a descriptive study structural basis for the recognition of sars-cov- by full-length human ace zoonotic origins of human coronaviruses the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak the incubation period of coronavirus disease 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what we know, how our patients should be treated now, and what should happen next covid- in diabetic patients: related risks and specifics of management prevention and management of covid- among patients with diabetes: an appraisal of the literature publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations conflict of interest the authors declare that they have no conflict of interest. key: cord- - lqlx rv authors: nan title: poster sessions date: - - journal: j diabetes doi: . / - . _ sha: doc_id: cord_uid: lqlx rv nan polycystic ovarian syndrome (pcos) is the most common endocrinopathy in women before menopause, the purpose of this study was to determine the effects of a diet and physical activity trial for improving pcos clinical and laboratory findings in obese women. this semi-experimental single-blind controlled trial was conducted among women with pcos ( cases and controls). initially, all the patients′ information was evaluated in terms of: demographic, menstrual status, clinical characteristics of hyperandrogenemia, as well as biochemical, hormonal and abdominal ultra-sonography. the intervention plan consisted of a -week exercise and diet program for the experimental group. all baseline assessments were repeated in both groups within months after beginning of the trial, and the results were analyzed. the comparison between the two groups revealed that in the experimental group, the interventions have been effective for the following variables: follicle stimulating hormone (p = . ), the luteinizing hormone (p = . ), total testosterone (p = . ), free testosterone (p = . ), estradiol (p = . ), selfglobulin band sex hormone (p = . ), triiodotyronine (p = . ), thyroxine (p = . ), tsh (p = . ), hydroxy progesterone (p = . ), triglycerides (p = . ), total cholesterol (p = . ), body mass index (bmi; p = . ), the ultrasound exam (p < . ), oligomenorrhea (p < . ), of hirsutism (p < . ), acne (p < . ) and alopecia (p = . ). it seems that regular exercise and dietary intervention are effective to improve pcos among obese women. a series of studies have recently demonstrated that the oxidative stress, nuclear factor-kappa b (nf-jb) activation and the subsequent coordinated inflammatory responses played an important role in the pathogenesis of urate nephropathy (un). polydatin has been suggested to have the properties of anti-oxidative, anti-inflammatory and nephroprotective effects. however, the possible protective and beneficial effects of polydatin on un are not fully elucidated. therefore, we investigated the potential beneficial effects and possible mechanisms of polydatin on un. in this study, polydatin showed inhibitory activities on xanthine oxidase to repress the level of serum uric acid in vivo and in vitro. further investigations revealed that polydatin displayed little toxic effects and significantly ameliorated the renal function in fructose-induced un mice. the nephroprotective activities of polydatin was not only due to the effects on remarkably attenuating the oxidative stress induced by uric acid, but also on markedly suppressing the oxidative stress-related inflammatory cascade, including decreasing the expressions of nf-jb p , cox- and inos proteins and inhibiting the productions of tnf-a, pge and il- β. these findings elucidated that polydatin exhibited prominent nephroprotective activities and low toxic effects. drug discovery, obetherapy, evry, france many obesity related genes have been proposed as targets for the treatment of obesity. however, these obesity genes did not provide efficient drug therapy for obesity treatment. this is mainly due to the redundancy of the biochemical pathway involved in obesity and the lack of specificity of the gene targets. it is therefore a challenge to identify crucial gene(s) targets involved in energy metabolism associated with "lean or starvation phenotype". congenital enteropeptidase defficiency is an extremly rare pathology which answer to all these criteria. enteropeptidase catalyzes the conversion of inactive trypsinogen into active trypsin via the cleavage of the acidic propeptide from trypsinogen. we have generated knock out transgenic mice for enteropeptidase which shows the same phenotype like in human. these data and in vivo preclinical data using per os small molecule for long term treatment ( weeks) will be presented. f. nasiri amiri , f. ramezani tehrani , m. simbar babol medical sciences university, babol, shahid beheshti university of medical sciences, tehran, iran polycystic ovary syndrome (pcos) is the most common chronic endocrine disorder with a prevalence estimated at - % depending on the diagnostic criteria used. it has significant and diverse clinical consequence including reproductive, metabolic, psychological morbidity and some cancer. it is unclear how pcos symptom influences such women's experiences of their bodies. this study aimed to explain women's experiences of their health concerns when living with pcos. this research is a qualitative study. semi-structured opened interviews were conducted with women aged - years who were diagnosed with pcos. interviewing the participants were continued to reach data saturation. all the interviews were recorded and transcribed. the data were analysed using content analysis. four closely intertwined themes were disclosed: physical consequences of pcos, fear of future, economic burden of desease and coming to terms with a chronic condition. our findings suggest that healthcare professionals working with pcos patients should consider providing peer support groups as a means to alleviate patients concern and to promote self management activities such as lifestyle modification. ideally, groups should be designed to meet patients support needs and expectations, and should be evaluated regularly. m. kidron , e. arbit oramed pharmaceuticals, jerusalem, israel, biomedical engineering, nyu -oramed pharmaceuticals, englewood, nj, usa introduction: the major cause of hyperglycemia in t dm is inappropriate, non-suppressible hepatic glucose production due to hepatic insulin resistance (hir)) and elevated glucagon levels. hir is a result of fat deposition in the liver which in turn begets a local inflammatory process, a common thread observed in t dm, the metabolic syndrome and obesity which are all known risk factors for morbidity. the only antidiabetic drug that addresses specifically hir, up to now is metformin and its effects wanes over time. there is an unmet need for other drugs that target the liver specifically. insulin has a direct effect on hepatocytic receptors and thus has shown to be capable to reduce hepatic steatosis and improve glycemic control, as well as reduce hepatic insulin resistance. insulin administered orally is absorbed into the portal-hepatic vein and reaches the liver at high concentrations. this route of administration may confer physiologic advantages over systemic insulin administration and lower the risk of hypoglycemia. results: bmi, hdl and cu levels were found to be significantly higher in women compared to men (p < . ). _ it was established that blood copper levels, similar to hscrp, predicted ms and ms parameters, but predicted different ms parameters at different sensitivities and specifities. we obereved that there was a more significant correlation between tg level, blood pressure and cu, compared to hscrp (tables , and ). conclusion: based upon these results, it may be stated that cu predicts ms and ms parameters as well as hscrp does and that it is even a better predictor for ms and atherosclerosis since it is less influenced from inflammatory events than crp. short-chain fatty acids which then up regulate proglucagon (precursor to glp ) and pyy gene. these gut hormones are collectively known as "incretin" and they primarily regulate insulin level after eating. very recently, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in type diabetes milliets. one is exenatide, long-acting agonist of the glp- receptor and other is incretin enhancer known as sitagliptin, a dpp inhibitor. however, glp- agonist reduces body weight (anti-obesity therapy) and leads to hypoglycemia. similarly, liraglutide, dpp-iv-resistant glp- receptor agonists is also synthesized using glp- sequence with prolongs half-life. in conclusion, polysaccharides might be a way to decrease the hurdle in diabetes managements and special attention should be paid to naturally derived polysaccharides. ms is often associated with inflammation caused by latent infections or sibo. we investigated whether treatments of such items may help to control ms. method: we prospectively studied patients presenting with ms and three concomitant causes of inflammation [helicobacter pylori (hp = cases); oral papillomavirus virus (hpv = ) or ebv ( ); sibo (h or ch breath tests: cases)] who were all successfully treated for hp, hpv or ebv, and sibo (decrease of h or ch > % and decrease of circulating th cells > % which are correlated with intestinal chronic inflammation). patients were followed-up months. conclusion: treatment of latent infection and sibo benefits mainly to patients younger than , without methanogenic flora and with few circulating th cells. and increases the gastric emptying time, intestinal transit time, gastric acid secretion in the ms bark juice treated group. there was significant (p < . ) decrease in the t max , t / and increase in the c max of met in ms bark juice treated group as compare to diabetic group. present study suggests that the bark juice of ms shows significant effects in the treatment of gastroparesis and it improves the pharmacokinetic of met compared to diabetic group of rat. type diabetes mellitus (t dm) is a complex metabolic disorder. its prevalence is expected to increase exponentially around the world. insulin resistance, inflammation and dysregulation of adipokines play a major role in the pathogenesis of t dm. among the huge growing adipose secretome, nicotinamide phosphoribosyl transferase (nampt) and vaspin emerged as novel interesting adipokines having insulinmimetic and -sensitizing effects, respectively. however, their role in t dm is still controversial. accordingly, this study was designed to investigate their levels in t dm patients compared to healthy control subjects, and to study the correlation between these two novel adipokines and the correlation between each of them with anthropometric parameters, insulin resistance, hyperglycemia, dyslipidemia, and also the inflammatory marker interleukin- (il- ). the levels of these two novel adipokines and other parameters were measured in non-obese and obese t dm patients together with matched healthy non-diabetic control subjects. the nampt, vaspin and il- levels were measured by elisa while insulin levels by chemiluminescence technique. the nampt and vaspin levels were found to be significantly elevated in non-obese ( . ae . and . ae . ng/ml, respectively) and obese t dm patients ( . ae . and . ae . ng/ml, respectively) compared to control subjects ( . ae . and . ae . ng/ml, respectively) at p < . . furthermore, nampt as well as vaspin were found to be significantly correlated with one another and with various metabolic parameters. in conclusion, nampt and vaspin are potential candidates to play important role in the development and progression of t dm. . to compare insulin resistance in sub-clinical and overt thyroid hypo-function. methods: one hundred eighteen patients with the diagnosis of hypothyroidism based on their clinical and thyroid function test profile were included in this cross sectional hospital based descriptive study with their informed consent. homa-ir as an index of insulin resistance was calculated for each subject from their fasting plasma glucose and serum insulin levels. autoimmunity against thyroid was evaluated by estimating anti tpo antibodies. results: homa-ir as an index of insulin resistance was comparable in overt ( . ae . ) and subclinical hypothyroidism ( . ae . ) but was above the reference range for this population. hypothyroid anti tpo positive cases has high tsh compared to negative cases in both overt hypothyroidism and subclinical hypothyroidism. conclusions: hypothyroidism induces insulin resistance but the degree of insulin resistance is not dependent on severity of thyroid hypofunction however is associated with autoimmunity against thyroid. . ae . in smoker and . ae . in non-smoker, insulin: . ae . and . ae . (p < . ), control: glucose level was . ae . in and . ae . mmole/l, insulin level: . ae . and . ae . mkiu/ ml, respectively. both growth in height and weight gain are accelerated during puberty. they are mainly affected by sex hormone, growth hormone and igf- , and influenced by various factors either directly or indirectly. the aim of this study is to find out the association of various cytokines with obesity and early-or precocious puberty in female children. twenty-eight female children with breast budding before years old, who underwent the lhrh stimulation test as well as cytokine analysis in their blood, were included in this study. the height, weight, and bmi were measured. we defined obesity when the bmi was percentile or more, and puberty when the maximum lh level was iu/l or more during lhrh stimulation test. adiponectin, leptin, ghrelin, il- β, il- , il- , resistin, and tnfa levels in the blood were analyzed by luminex multiple bead technology (milliplex; millipore co., billerica, ma, bio-plex; bio-rad laboratories, hercules, ca). nineteen out of children were categorized as having early-or precocious puberty. their mean il- level was lower in pubertal children than that in prepubertal state ( . ae . vs. . ae . , p = . ). the leptin and resistin levels were significantly higher in obesity group (n = ) than in non-obesity group, while the ghrelin was significantly lower in obesity group (p < . ). in conclusion, the female children younger than years of age in early-or precocious puberty did not show the increment of leptin or resistin comparing with the female prepubertal children, although the obesity group showed significantly higher levels of leptin and resistin. aims: arterial stiffness is independent risk factor of cardiovascular events. suggest that the statins benefit associated with improvement in arterial stiffness parameters beyond lipidslowering effects. to evaluate changes in pulse-wave shape in obese high risk patients with ah and dyslipidemia treated with rosuvastatin compared with atorvastatin. methods: eighty-two obese patients (age . ae years) with ah, dyslipidemia were randomized to atorvastatin group (n = ) or rosuvastatin (n = ). acei and thiazide diuretics added blood pressure control. pulse-wave characteristics measured before and after weeks of treatment using finger photoplethysmographic device. stiffness index (si), reflection index (ri), augmentation index (aix), systolic bp in aorta (spa), digital pulse amplitude augmentation (paa) were accessed. results: before the treatment impared si, elevated ri, aix, spa were shown. lipids and bp goals were achieved in all patients validating further analysis. decrease in si (d si, м/c À . atorva and À . rosuva), ri (dri, % À . atorva and À . rosuva) were revealed in both treatment arms (p > . ), whereas significant trends towards aix decrease were demonstrated only in rosuvastatin-treated patients (dai, % À . atorva and À . rosuva, p < . ) rosuvastatin group demonstrated better increasing in paa than atorvastatin group (paa (atorva): before treatment . ae . and after weeks: . ae . , p = . vs. paa (rosuva): before . ae . and after weeks . ae . , p < . ). conclusions: pulse-wave analysis in obese ah patients demonstrated increasing vascular stiffness. both atorvastatin and rosuvastatin treatment resulted in arterial stiffness parameters, whereas only rosuvastatin treatment was significantly associated with trends in aix and paa improvement in short-term follow-up. z. wang , m. xu methods: four thousand two hundred and twenty-six adults above years of age and adults under years from a cohort investigated in - at the medical examination center of zhongnan hospital were recuited. cases of fld was identified through ultrasound imaging. the risk factors measured were bmi, and plasma concentrations of alt, ast, tc, tg, hdl, ldl and serum uric acid (sua). the probability of steatohepatitis with advanced fibrosis was calculated according to the body mass index, age, alt, and triglyceride (baat) and ast/alt ratio (aar). results: the prevalence of fld was higher in elderly ( . %) than in non-elderly ( . %) and similar in elderly between men and women ( . % vs. . %, p > . ). multiple regression analyses showed that obesity, high tc, tg, sua, low hdl, and elevated alt, aar < were closely related to the elderly fld the prevalence of steatohepatitis estimated as baat index ! was . % in all subjects, and was higher elderly fld patients than in the non-elderly fld patients. conclusion: the prevalence of fld is higher in the elderly, and is broadly related to the same metabolic risk factors as in the nonelderly. however, female-sex is no longer protective with increasing age, and the prevalence of steatohepatitis with advanced fibrosis is estimated to be considerably higher in the elderly fld patients than in the non-elderly fld controls. vanderbilt, nashville, tn, usa bariatric surgery improves glucose tolerance and may be a viable strategy to prevent the progression from obesity-induced insulin resistance to overt diabetes; however, the recurrence of diabetes is significant following the surgery. we sought to determine whether gastric bypass surgery protected pancreatic beta cells and prevented disease progression to overt diabetes. gastric bypass (roux-en-y gastric bypass, rygb) was performed in young ( weeks old) prediabetic blks db/db null (bks-db) mice, young ( weeks old) new zealand obese (nzo) male mice that were fed high-fat diet (hfd) post-surgery, c bl/ db/db null (b -db) mice that developed insulin resistance, and streptozotocin (stz)-induced diabetic mice. rygb resulted in sustained normoglycemia and improved glucose tolerance in pre-diabetic bks-db mice and hfd-fed nzo mice. remarkably, rygb preserved beta-cell mass and increased plasma insulin with reduced beta-cell apoptosis which was independent of weight loss and body fat reduction. rygb neither reversed hyperglycemia when performed in diabetic bks-db and nzo mice nor resulted in resolution of diabetes in stz-induced diabetic mice. the results demonstrate that gastric bypass prevents beta-cell failure if performed prior to onset of severe beta-cell damage in genetic obese mice. l. ruzic , g. sporis , m. prasek sport and exercise medicine, applied kinesiology, faculty of kinesiology, university of zagreb, vuk vrhovac university clinic, zagreb, croatia the aim of the study was to examine the influence of strength training program on pre-and post workout glycemia. twelve able-bodied diabetic patients using insulin pump (mean age . ae . , m/ f) were enrolled into gym programs /week ( min warm-up aerobic workout, intensity at % hrmax plus strength training exercises involving different muscle groups) for months. no other interventions were introduced. we were interested in effects of the programe on pre-and post workout glycemia, so the comparisons between the first weeks and the last weeks of the study were performed. also the subjects were asked about hypoglycemic episodes. there was a great variability observed in pre-and post glucose concentration within and between subjects. the mean pre-workout glucose concentration in the first weeks of the program was . ae . vs. . ae . mmol/l in last weeks of the program and the difference was not significant (p = . ). nevertheless, the mean glucose decrease after workout was higher in the last weeks of the program (deltaglu: . ae . vs. . ae . mmol/l; p < . ). no hypoglycemic episodes were reported. the months strength training program did not influence large variability in glucose levels before the workout as it depends on many other factors. the only observed effect were larger pre-to post workout glucose differences. it seems that over the time, the strength training may stimulate the body to use more glucose during the workout, which might be explainable with the expected increase of lean body mass. aim: the aim of this study was to evaluate the level of c-reactive protein in gestational diabetes mellitus. materials and methods: sixty-five healthy pregnant women aged . ae . years between the th and th weeks of gestation were studied. all women referred for a -g oral glucose tolerance test following an abnormal result on a screening. the demographic data, waist circumference, height, and weight of the participants were recorded. fasting levels of insulin, triglycerides (tg), c-reactive protein (crp), fasting blood glucose (fbg) and hba c were measured. results: based on oral glucose tolerance testing participants were divided into two groups: normal glucose tolerance (ngt; n = ) and gestational diabetes mellitus (gdm; n = ). the mean crp level was highest in gdm group ( . ae . mg/l), followed by ngt ( . ae . mg/l), (p < . ). the mean fbg ( . ae . vs. . ae . mmol/l, p < . ), homa-ir ( . ae . vs. . ae . , p < . ) and tg levels ( . ae . vs. . ae . mmol/l, p < . ) in the women with gdm were significantly higher than those in the ngt group. methods: in , an observational, prospective study started in france on request of the health authorities (has). one thousand seven hundred and two type diabetic patients treated by vildagliptin were recruited through a national representative sample of gps and diabetologists. we report the data of interim analyses after months of follow-up. results: one thousand four hundred and sixty-three patients are included in this interim analysis: % males, aged ae years, with mean bmi of kg/m . hba c was equal to . ae . % at vildagliptin initiation, then . ae . %, . ae . % and . ae . %, while mean weight decreased from to , and kg at , and months respectively. vildagliptin, rarely prescribed when not recommended, was well tolerated: asat and/or alat were > ui in . % at initiation of vildagliptin then . % at months, with a slight decrease for mean asat and alat. mean gfr was ml/mn at initiation of vildagliptin then ml/mn at months, with a stable percentage of gfr < ml/mn ( %) and < ml/mn ( . %). six severe hypoglycemic episodes occurred in six patients (incidence = . / patient-years), all treated by insulin and/or sulfonylurea in addition to vildagliptin. the proportion of patients still treated by vildagliptin at months was . %. conclusions: over months, in real-life conditions of care, vildagliptin showed a sustained effectiveness in terms of hba c reduction, a good tolerance, very few severe hypoglycemic episodes, rare treatment discontinuations and was most often prescribed as recommended. background: hdl lipoproteins are known to play a causative role in atherosclerosis and its clinical manifestation-coronary artery disease (cad). carotid intima media thickness (imt) is considered as a marker of atherosclerosis and in prediction clinical coronary events. aim: to determine the associations between plasma lipids and subclinical atherosclerosis measured by the common carotid intimamedia thickness (imt) in cad patients. methods: hdl subclasses were separated with - % pag electrophoresis, and imt was determined using high-resolution b-mode ultrasound in cad patients, with normal levels of traditional lipid risk factors. results: mean value of left and right carotid artery measurement was selected as value for correlation with hdl subclass size in each patient. the mean hdl size was . ae . nm, and the mean imt in all patients was . ae . mm ( . - . mm). hdl size was not correlated with imt (r = À . ; p > . ). by univariate analyses, carotid imt was the most closely related to systolic pressure (r = . , p < . ), followed by diastolic pressure (r = . , p < . ) and age (r = . , p < . ). stepwise multiple linear regression analysis revealed that diastolic pressure (β = . , p < . ), systolic pressure (β = . , p < . ) and age (β = . , p < . ) were independent predictors of determining carotid imt (adjusted r < . , p < . ). conclusion: these results indicate that diastolic pressure, systolic pressure and age are an important, independent determinants of carotid imt in cad patients. no other traditional risk factors imparted imt. objective: antinuclear antibodies (ana) are present in approximately - % of patients with non-alcoholic steatohepatitis (nash). a recent study implied the relationship between obesity and autoimmunity. the purpose of this study was to investigate the relationship between seropositivity for ana and metabolic abnormalities including insulin resistance, obesity and hepatic steatosis in patients with nash. methods: the severity of hepatic steatosis and fibrosis was scored by the nafld activity score system. seropositivity for ana was defined as titers of : or higher by an indirect immunofluorescence method using hep- cells. insulin resistance and obesity were evaluated by the value of homa-ir and bmi, respectively. the diagnosis of autoimmune hepatitis (aih) was based on the simplified scoring system. results: nine ( %) of patients with nash had ana. overall bmi in nash patients with ana was higher than that in those without ana. laboratory analyses revealed significantly higher mean igg level ( ae vs. ae mg/dl, p = . ) and the mean value of homa-ir ( . ae . vs. . ae . , p = . ) in nash patients with ana than those in those without ana. histological examinations exhibited that nash patients with ana had higher scores in hepatic steatosis ( . ae . , vs. . ae . , p = . ) and fibrosis ( . ae . vs. . ae . , p = . ) than those without ana. however, none of nash patients fulfilled the criteria for "definite" aih. conclusion: nash patients with ana had clinical characteristics of significantly higher serum igg levels and severe insulin resistance, and they tended to have more severe obesity, hepatic steatosis and fibrosis than nash patients without ana. r.f. alponti , , p.f. silveira pharmacology, instituto butantan, physiology, instituto de biociencias/universidade de sao paulo, sao paulo, brazil introduction: although irap (ec . . . ) is well-known, the existence of other aminopeptidases (aps) related to energy homeostasis remains unclear. objectives: to search a diverse array of aps in high (hdm) and low (ldm) density microsomes and in plasma membrane (mf) of retroperitoneal adipocytes from healthy control (c), monosodium glutamate (msg) obese and food deprived (fd) rats with their in vitro responses to insulin (is), vasopressin (avp), angiotensin (ang)-ii and ang-iv. methods: ultracentrifugation and spectrofluorometry. results: dipeptidyl-peptidase-iv (dppiv) and aps basic (apb), neutral puromycin-sensitive (psa) and -insensitive (apm), and methionyl (metap) were found. compared with non-stimulated, these aps were unaffected by is; avp increased apb/apm (ldm) and dppiv/psa (hdm) of msg-fd and metap/psa (hdm) of c; ang-ii increased apm (fm-ldm) of c, dppiv (fm) of msg and psa (fm) of fd; ang-iv increased apb (fm) of fd, apm (hdm) of msg and dppiv (fm) of c and msg. aps were modulated by avp in hdm-ldm, by ang-ii in fm-ldm and by ang-iv in fm-hdm. compared with ldm, metap decreased in fm of c and increased in fm of msg-fd without peptide stimuli; and only diabetes-related enzyme dppiv exhibited peptide-mediated intracellular translocation, which was from ldm to hdm (stimulated by avp) in msg-fd, and from ldm and hdm to fm in msg and msg-fd (stimulated by ang-ii) and in c and msg (stimulated by ang-iv). conclusion: novel peptide-modulated apb, apm, psa, metap and dppiv are found in adipocyte, this last with altered subcellular trafficking under metabolic distress. supported by fapesp, cnpq and capes. nutritional and environmental sciences, university of shizuoka, shizuoka city, japan previous studies have suggested that (-)-epigallocatechin- -gallate (egcg) exerts antioxidative and anti-inflammatory actions in various tissues, which might be beneficial for reducing risks of development of diabetes. however, an optimum intake level of egcg is unknown. in this study, we have examined the effect of a diet containing egcg on the expression of inflammation-related genes in various tissues including visceral adipose tissue and the muscle of non-obese type- diabetes animal model, goto-kakizaki (gk) rats. gk rats at weeks of age were fed a control high-fat diet ( energy% as fat) or the high-fat diet containing . %, . % or . % egcg for weeks. the mrna and protein levels of il- β, il- , mcp- , cd s, il- , tnf-a, resistin and pai- were significantly reduced in the adipose tissue of rats fed a diet containing . % egcg, but not in those fed diets containing . % or more egcg, as compared with control. the mrna levels of tnf-a, ifn-g, il- b, il- and il- in the muscle of rats fed a diet containing . % egcg were also significantly lower than those in the control. these results suggest that there is an optimum range of intake of egcg, which may suppress the expression of genes involved in inflammation in the adipose tissue and the muscle. diabetes and hypertension are the most relevant factors leading to vascular disease and cardiovascular problems. since both pathologies are greatly increasing nowadays, there is a need to detect at early stages the occurrence of target organ damage associated with them. this is the relevance of identifying biomarkers that can detect or predict the onset of cardiovascular and renal damage associated with diabetes and hypertension. given that the role of osteoprotegerin in bone metabolism is well known, and some evidence of its putative relationship with diabetes-associated pathologies has been found, to this date there is no evidence linking this molecule with target organ damage associated with diabetes. in this study, we analyze whether osteoprotegerin may be used to detect and evaluate cardiovascular and renal pathologies associated with diabetes in an in vivo model. we used normotensive and hypertensive rats, a subset of rats of each group receiving a single streptozotocin injection in order to induce diabetes. we performed an -month followup, periodically collecting blood and urine samples and monitoring both blood pressure and blood flow in the lower limbs. our results showed that osteoprotegerin was associated with the presence of diabetes, suggesting that it might be used as a biomarker for the occurrence of cardiovascular damage or to detect cardiovascular risk under these circumstances. blood flow in the lower limbs decreased soon after diabetes onset, as osteoprotegerin levels increased. our data suggest the potential use of serum levels of osteoprotegerin as a biomarker for diabetes and hypertension-associated endothelial dysfunction. purpose: this study examined whether breakfast meal composition alters the incretin response and glycemic control following both the breakfast and lunch meal. methods: seven subjects with t d completed two conditions where they consumed either a kcal high protein (pro: % carbohydrate, % protein, % fat) or high carbohydrate (cho: % cho, % protein, % fat) breakfast for days of acclimatization. on day , they underwent meal testing in which they consumed the respective breakfast followed by a lunch meal ( kcal: % cho, % pro, % fat). blood samples were collected over the -h period and analyzed for glucagon, insulin, glucagon-like peptide- (glp- ) and glucose-dependent insulinotropic polypeptide (gip) concentrations. incremental area under the curve (iauc) for the -h post-breakfast and -h post-lunch period was calculated. results: the iauc for insulin, glucose and glp- were not significantly different between conditions or between meals. the gip response to the pro breakfast ( ae pg/ml*min for -h) was lower (p = . ) compared to the cho breakfast ( ae pg/ ml*min for -h), with the opposite effect occurring in response to the lunch meal (pro: lunch ae ; cho: lunch ae pg/ ml*min for -h, p < . ). conclusion: despite no differences in glucose and insulin levels, a pro breakfast, compared to a cho breakfast, resulted in lower gip levels for the initial meal with a greater second meal effect after a lunch meal. however, a pro breakfast potentiates gip levels after a lunch meal. further research is needed to determine the physiological role of changes in circulating gip. high risk pregnancy, kasralainy university, cairo, egypt background: pregnancy tends to reset the glucose homeostasis in the direction of diabetes. about - % of all pregnant women develop an abnormal glucose tolerance in pregnancy, but most often glucose tolerance returns to normal postpartum. this condition is called gestational diabetes mellitus (gdm). aims: comparative study between gestational and pregestational diabetes in relation to glycemic control as regarding fetal and neonatal outcome. methods: this study was conducted in kasralainy maternity hospital from september to march and it included pregnant women complicated by dm attending outpatient clinic or inpatient. patients were classified into two groups, gestational diabetes: pregnant women complicated by dm which is diagnosed for the first time during pregnancy and pregestational diabetes: pregnant women who have dm that has been diagnosed prior to pregnancy. the two groups were compared according to fetal (macrosomia and intrauterine fetal death) and neonatal (respiratory distress syndrome and birth injuries) complications. all patients were - years old, singltone pregnancy, with time of termination after completed weeks. results: fetal macrosomia occurred more with gdm, on the otherhand birth injuries and rds occurred more with pre-gdm. macrosomia and rds were commoner among poor glycemic control in pregnant diabetic females than birth injuries and iufd. conclusions: glycemic control started as early as possible (the best being preconceptional) is important to decrease the incidence of birth injuries, macrosomia, fetal mortality, the need for nicu admission (rds). adiponectin, an adipocyte-derived hormone, is implicated in type diabetes and atherosclerosis. this study was designed to investigate whether serum adiponectin levels in coronary artery disease (cad) patients with type diabetes (t dm) are lower than in patients with cad alone and healthy controls. we measured serum adiponctin levels in subjects, patients with cad ( subjects of whom had both cad and t dm), and also healthy subjects were selected as controls. all patients were subjected to anthropometric indexes assessment and biochemical measurement of serum adiponectin, interleukin six (il- ), insulin, lipid profile and glucose by standard methods. the results revealed significant differences in serum adiponectin levels between cad patients with t dm and cad patients without t dm ( . ae . vs. . ae . lg/ml, p = . ), between patients with cad and healthy controls ( . ae . vs. . ae . lg/ml, p = . ), and between men and women ( . ae . vs. . ae . , p = . ). serum adiponectin levels were correlated significantly with insulin, total cholesterol, low density lipoprotein, body mass index, glucose, homa-ir, il- (r = À . , p = . , r = À . , p = . ; r = À . , p = . ; r = À . , p = . ; r = À . , p = . ; r = À . , p = . ; r = À . , p = . , respectively). adiponectin was correlated positively only with high density lipoprotein (r = . , p = . ). conclusions: we conclude that low serum adiponectin levels and insulin resistance coexist in cad patients with t dm. it is speculated that subjects who have very low levels of serum adiponectin may be at increased risk of developing both t dm and cad. objective: to simultaneously examine the impact of self-reported and newly-identified hypertension upon subsequent type diabetes (t d). methods: two community-based adult prospective cohort studies, with the same protocols, instruments and questionnaires, were conducted during - and - in urban areas of nanjing, china. data from these two cohorts were pooled and analyzed. t d (outcome variable) was identified using the world health organization diagnosis criteria. based on status of blood pressure (independent variable), participants were categorized into three groups: (i) people with normal blood pressure at baseline survey and during follow-up period (normal blood pressure), (ii) subjects with self-reported hypertension at baseline survey (self-reported hypertension) and (iii) those who did not report hypertension at baseline but were diagnosed having hypertension during follow-up period (newly-identified hypertension). all covariates were assessed at baseline and in the third-year follow-up survey. results: among participants, the -year cumulative incidence of t d was . %, . % and . % for participants with newly-identified hypertension, self-reported hypertension and normal blood pressure, respectively. after adjustment for potential confounders, compared to people with normal blood pressure, participants with newly-identified (or = . ; %ci = . , . ) or self-reported (or = . ; % ci = . , . ) hypertension were more likely to develop t d. furthermore, subjects with newly-identified hypertension (or = . ; % ci = . , . ) were at elevated risk of developing t d relative to their counterparts with self-reported hypertension. the similar associations of hypertension with t d were also found in both men and women, separately. hypertension, either self-reported or newly-identified, is an independent risk factor for developing t d among urban chinese adults. methods: a total of patients with type diabetes receiving standard glucose-lowering therapy were enrolled. efficacy of the lowcalorie diet ( kcal/day) with inclusion of specialized nutrison advanced diason product was assessed in two similar groups in during weeks: main group patients (n = ) received diet with nutrison advanced diason in the amount of ml as the only food for the day twice a week for weeks; control group patients (n = ) received a low-calorie diet with the inclusion of a standard meal at calories twice a week. results: the average weight loss in the main group was ae g, in the control group - ae g per day. according bioimpedance complex therapy with specialized product increased the content of lean mass by an average of . ae . kg and decreased fat mass by an average of . ae . kg. in main droup was a reduction of the basal level of glucose to . ae . - . ae . mmol/l (p = . ), in control groupfrom . ae . to . ae . mmol l (p = . ). total cholesterol level in the main group decreased from . ae . to . ae . mmol/l (p = . ), in the control groupfrom . ae . to . ae . mmol/l. the inclusion of the specialized product nutrison advanced diason in the standard low-calorie diet allows to raise the efficacy of dietary therapy in patients with type diabetes. liver injury and regeneration involve complicated processes and are affected by various physio-pathological factors. this study was designed to investigate the mechanisms of steatosis-associated liver injury and impaired regeneration in a mouse partial hepatectomy model. male c bl/ j and db/db mice were used as mice with normal and steatotic liver, respectively. liver regeneration and injury were evaluated chronologically after hepatectomy. initial regeneration of the steatotic liver was markedly impaired after hepatectomy. although hepatocyte proliferation was not significantly suppressed, intense liver injury with oxidative stress occurred immediately. fasl/fas expression was up-regulated in the steatotic liver, whereas the expression of anti-oxidative and anti-apoptotic molecules (catalase/mn-sod/ref- and bcl- /bcl-xl/flip, respectively) and p /sqstm , a steatosis-associated protein, were down-regulated. interestingly pro-survival akt was not activated/phosphorylated in response to hepatectomy though it was sufficiently expressed/ phosphorylated even before hepatectomy. suppression of p /sqstm increased fasl/fas-expression and reduced nrf- -dependent are activity and anti-oxidative responses in steatotic and non-steatotic hepatocytes. exogenously added fasl induced intense cellular oxidative stress and necrosis/apoptosis in steatotic hepatocytes, only the necrosis being inhibited by pretreatment with anti-oxidants, suggesting that fasl/fas-induced oxidative stress mainly leads to necrosis. furthermore, p /sqstm re-expression in the steatotic liver markedly reduced liver injury and improved tissue regeneration. in the steatotic liver, reduced expression of p /sqstm induced fasl/fas expression and suppressed anti-oxidant genes through nrf- inactivation, which together with hypo-responsiveness of akt, caused post-hepatectomy necrotic and apoptotic liver injury in redoxdependent and -independent manners, respectively. p /sqstm may be a key molecule in post-hepatectomy acute liver injury and impaired regeneration in fatty liver in mice. objective: mastication can accelerate satiety sensation and lipolysis through activation of histamine neurons; however, the data on antiobesity effects of mastication are limited. we therefore examined the effect of chewing on postprandial satiety and energy metabolism in humans. methods: satiety, energy expenditure, and fat oxidation were measured in lean young women on separate occasions, before and h after consumption of a solid meal with chewing per bite or after swallowing the same mashed meal without chewing, in a randomized, crossover design. each test meal consisting of kj ( % of energy as carbohydrate, % of energy as protein, and % of energy as fat) was consumed between and min regardless of texture difference. the thermic effect was greater after the solid meal ( . ae . %) than after the mashed meal ( . ae . %, p < . ). time course of fat oxidation tended to be higher after the solid meal than after the mashed meal (p = . ). in addition, solid meal was more satiating than mashed meal (p = . ). the results suggest that mastication contributes to postprandial satiety and thermic effect of meal. chewing meal thoroughly could be a useful eating behavior for preventing weight gain. introduction: raven noted an association between insulin resistance and cardiovascular consequences and type dm. mathew prescribed the method of insulin resistance designation using mathematic model homa-ir. aim: to estimate insulin resistance homa-ir in adult population according to gender, assess selected parameters in people with homa-ir ! . (i group) and homa-ir < . (ii group) and determine dependence between homa-ir and the above parameters. materials and methods: one hundred and fifty-four people medium age . years, from tarnawa city constituted the material. bp was examined. blood samples were obtained for plasma glycaemia, lipidogram and serum insulinaemia. all people were measured and weighed, bmi and homa ir were calculated, waist circumference was obtained. the cut-off point . for homa-ir was accepted. results: . % of the examined population had insulin resistance without a difference between women and men. significant differences between i and ii group were observed according to tg and waist circumference. in women all examined parameters were significantly different except hdl. in men bmi, waist circumference and hdl were significantly different in i and ii group. in the female group correlations between homa ir concerned all examined parameters, in the male group-hdl and waist circumference. conclusions: there was no significant difference between women and men according to insulin resistance in the whole study group. the difference between selected parameters in the two examinated groups were more strongly in women. body mass was the main factor determining insulin resistance in the whole study group as well as in men and women. background: the immune system is altered in obesity and diabetes, through changes in adipocytes, liver, pancreatic islets, vasculature and circulating leukocytes, with increased cytokine and leukocytes activation, suggesting inflammation participation in diabetes. minocycline presents a potent anti-inflammatory activity, as evaluated in vivo and in vitro. objectives: minocycline anti-diabetic effects were assessed in alloxaninduced diabetes through biochemical parameters measurements, histological and immunohistochemistry analyses. methods: alloxan was injected to rats, blood collected h later and after oral treatments ( , and days) for glycemia, triglycerides, cholesterol and transaminases measurements. diabetic controls and diabetic plus minocycline ( and mg/kg) or glibenclamide ( mg/ kg) were used. furthermore, pancreas, liver and kidney were submitted to histological and immunohistochemistry (cox- and tnf-a) analyses. results: decreases in glycemic and triglyceride levels, at the th and mainly th days after minocycline treatments, were observed. he staining showed that minocycline partly reversed tissue alterations, and decreased expressions of cox- and tnf-a, as compared to untreated animals. conclusions: beneficial minocycline effects in diabetes could be due to its anti-inflammatory and antioxidant properties and, by inhibiting microglial activation, it may be an important therapeutic strategy in diabetes where inflammation plays a significant role. methodology: forty-eight hours after alloxan-induced diabetes, blood from male wistar rats was collected for biochemical measurements. then, diabetic rats untreated or treated ( week, or months) with pentoxifylline ( , , and mg/kg, p.o.) or glibenclamide ( or mg/kg, p.o., alone or associated to pentoxifylline) were divided into eight groups with - animals each. after treatments, biochemical measurements were repeated. glycated hemoglobin determinations, and histological and immunohistochemistry analyses for inos were also performed. results: pentoxifylline brought hyperglycemia and triglycerides towards normality. glycated hemoglobin was improved. the use of diazoxide showed the mechanism of action of pentoxifylline partly related to atp-dependent k + channels. pentoxifylline improved histological alterations in pancreas, liver and kidney, and decreased inos cell expression. conclusions: pentoxifylline effects are probably related to its action on oxidative stress and inflammation, decreasing pro-inflammatory cytokines. thus, pentoxifylline is a potential candidate for diabetes mellitus therapy, since patients with vascular complications present beneficial effects, as shown in clinical practice. recently, a close relationship between the development of adiposity and gut-derived hormonal dysregulation has been clearly established. for instance, studies of gut-derived peptides such as pyy - , glp- , oxyntomodulin, discovered more than years ago and, later on ghrelin have significantly improved our understanding of mechanisms underlying ectopic lipid infiltration in organs and tissues. the etiology of non-alcoholic fatty liver disease (nafld) is intimately related to the capacity of hepatocytes to acquire an "adipocyte-like" phenotype. we previously reported that unacylated ghrelin (uag) is more potent than acylated ghrelin (ag) to stimulate adipogenesis. the present study intends to investigate the relevance of uag and ag as mediators of lipid accumulation in hepatocytes. hepg hepatocytes were treated with a control, uag or ag ( nmol/l and pmol/l) in the presence or absence of oleate ( nmol/l) to measure lipid droplet (ld) number and size. gene expression analyses were performed for key mediators of pre-adipocyte differentiation or liver functions. in response to uag or ag treatment in the presence or absence of oleate, ld number was markedly increased in hepg cells. similarly, increased ld size was noted following the treatment of hepg cells with uag or ag. however this effect could not be detected in the presence of oleate. gene expression of ppar-c and c/ebp-a was increased while that of ppar-a was decreased in response to ag treatment. these results are first to describe mechanisms through which uag and ag could promote the development of lipid infiltration in liver. deakin university, melbourne, vic., australia the world health organization believes that type diabetes mellitus is an important public health problem in the world. however some statistics showed that only . % of all world population had diabetes in , but the health professionals argue, this amount will reach to % in . diabetes australia -nsw estimates that almost million australians have diabetes and also around . million australian populations are at risk of this disease and unfortunately, the number of australian with diabetes will be approximately . millions in . obviously, direct and indirect medical costs due to health care of diabetic's patients are very high and % of the australian government's health budget is spent on health care of type diabetes. therefore, the health professionals have tried to provide the optimal public health programs for control and management of type diabetes. many researchers and health professionals argue that control of weight by change diet habits and exercise are major keys in lifestyle programs for prevention of type diabetes. in this case, the results of several studies like the finnish study, american study, the swedish malmo study and chinese study showed that the focus on diet and exercise programs are significant approaches in type diabetes prevention, while some other studies claim that the change diet habits and exercise may not sufficient and some medicines for control of insulin sensitivity and energy expenditure may also be necessary. therefore, lifestyle intervention programs and pharmacologic intervention programs are the major prevention programs. objectives: metabolic responses to acute endurance exercise may be affected by time of day because the nervous and endocrine systems have circadian rhythms clearly. the purpose of this study was to investigate the influence of acute endurance exercise in the morning and evening on metabolic responses in young men. methods: ten healthy young men completed two trials in a randomized cross-over design: . morning ( : - : ) and . evening ( : - : ) trials. in the morning and evening trials, participants walked for min at % of maximal oxygen uptake on a treadmill. pulmonary gas exchange was determined breath-by-breath by a gas analyzer. blood samples were collected to determine hormones and metabolites at preexercise, immediately and h after exercise. results: plasma interleukin- and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (p < . and p < . , respectively). serum growth hormone concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (p < . ). serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at h after exercise (p < . ). however, there was no significant difference in fat oxidation between the morning and evening trials. conclusion: these findings suggest that acute endurance exercise in the evening is more effective on lipolysis compared to that in the morning in young men. nutrition, school of public health, university of sao paulo, sao paulo, brazil background: the rs snp of fto (t>a) has been associated with obesity and its comorbidities. in a allele carriers, physical activity (pa) minimizes the deleterious impact on body weight, which could reduce cardiovascular risk. objectives: to investigate whether pa level and television viewing modulate the effects of a allele of fto on adiposity and markers of inflammation in individuals at high cardiometabolic risk. methods: this cross-sectional study included prediabetic individuals ( women, . ae . years, bmi . ae . kg/m²). physical activities were measured by the long-version of ipaq; individuals were genotyped and stratified according to total pa (< or ! min/week) and television watching (< or ! h/week). anthropometric, biochemical and inflammatory data were obtained. subgroups of individuals with or without a allele were compared by student's t test. results: among individuals who watched tv < h/week, those carrying the a allele had significantly higher concentrations of total and ldl-cholesterol, apolipoprotein b ( . ae . vs. . ae . mg/dl) and interleukin- ( . ae . vs. . ae . pg/ ml), but did not differ regarding anthropometric measures. among those who watched tv ! h/week, no difference in any clinical data was detected comparing carriers and non-carriers of a allele. regarding pa, the presence of the variant allele did not influence the metabolic profile. the presence of the variant allele at fto gene seems to favor a deleterious metabolic and inflammatory profiles particularly for individuals less exposed to sedentary activities such as watching tv. for inactive individuals, the allele presence might not affect predisposition to adiposity-induced disturbances. cardiovascular disease is the leading cause of death in brazil and in the world and its development is directly related to lifestyles and habits acquired in childhood. the objective of this study was to evaluate the anthropometric data and blood pressure levels of schoolchildren to verify that the body mass index and waist circumference maintain a relationship with blood pressure. the descriptive study was conducted with schoolchildren of both sexes in schools of cruzeiro do oeste, a small town in southern of brazil. the evaluations consisted of: measurement of weight (w) and height (e) to calculate the body mass index (bmi), waist circumference (wc) and blood pressure (bp). associations between variables were determined using the chi-square test. we observed a high percentage of overweight, wc modified and high pressure measurements. both bmi and wc showed significant association with the high pressure measurements. there is an association between increased blood pressure and increasing age. increases in bmi and central adiposity are associated with higher risks of high pressure measurements, and consequently other chronic diseases in - years old children. this study, descriptive and cross-sectional, had as objective to evaluate the relationships between anthropometric measures and lifestyle habits with the lipid profile of brazilian schoolchildren (n = ). the variables obtained were: weight and height to calculate body mass index (bmi), waist circumference (wc), blood pressure (bp), physical activity and dietary habits, serum lipid profile and glycemia. the results were analyzed by the mann-whitney test, the chi-square test and a relative measure of effects odds ratio. the significance was set at % (p < . ). anthropometric variables showed . % of schoolchildren are overweight, . % showed elevated levels of total cholesterol. there was no significant association between nutritional status and lipid profile. this evidence suggests that an appropriate bmi is not indicative of the absence of changes in lipid profile components. the risk factors associated with the development of cardiovascular disease among the children evaluated were: absence of mean meals, lack of daily physical activity, physical activity < times a week, and the consumption of salty snacks more than four times a week. the physical activity was negatively associated with dyslipidemia, suggesting that physical activity may underlying mechanisms by which zinc and magnesium influence glucose metabolism involved oxidative stress and inflammation. this crosssectional study investigated whether intakes of zinc and magnesium are useful to indicate oxidative stress, inflammation and insulin resistance in individuals at cardiometabolic risk. two hundred and five individuals ( . ae . years) with pre-diabetes were evaluated regarding dietary ( -h food recalls) and clinical variables and compared according to zinc and magnesium intake tertiles by anova. multiple linear regression analysis was employed including adjustments for age, gender and bmi (model ), and saturated fat acid intake, smoking status and physical activity (model ). stratified according to tertiles of magnesium intake, no significant differences in anthropometric, plasma glucose, lipid variables, superoxide dismutase (sod), oxidized ldl, inflammatory markers and homa-ir were found. mean values of fat mass ( . ae . . ae . . ae . %) and homa-ir ( . ae . . ae . . ae . ) were significantly lower in the highest tertile of zinc intake; significant trends to decrease fat mass, homa-ir and c-reactive protein were also observed (p-trend < . ). in linear regression models, intakes of both micronutrients were inversely associated with homa-ir but not with inflammatory markers. direct associations were found between magnesium intake and sod concentrations in adjusted models. our findings suggest that assessment of zinc and magnesium intakes may indicate oxidative stress, inflammatory status and insulin resistance in at risk individuals. our design does not allow establishing cause-effect relationship. longitudinal studies are needed to clarify if increased consumption of these micronutrients would ameliorate these pathophysiological processes. a. cezaretto, b. almeida-pititto, c.r. barros, a. siqueira-catania, s.r.g. ferreira nutrition, school of public health/university of sao paulo, sao paulo, brazil introduction: lifestyle changes remain a major challenge for reducing cardiometabolic risk. psychological disorders coexist with risk factors such as unhealthy life habits, decreasing quality of life (qol) and favoring dropouts during interventions. objectives: to compare clinical and psychological characteristics of individuals who dropped or not from lifestyle interventions, traditional or interdisciplinary. methods: one hundred and eighty-three prediabetic individuals ( . ae . years; bmi . ae . kg/m²) were allocated to month interventions on diet, physical activity and stress management. traditional intervention was based on quarterly medical visits, while participants of interdisciplinary intervention also had psychoeducative group sessions. depressive symptoms were assessed by the beck depression inventory (score ! ) and qol by the sf- . independent t-test was used to compare dropouts and non-dropouts. results: body adiposity, blood pressure, fasting glycemia, lipids, depression and qol improved in both interventions, but, in general, improvements were greater in the interdisciplinary intervention. comparing baseline data of dropouts and non-dropouts at the th month, dropouts of traditional intervention had higher bmi ( . vs. . ; p = . ), depression score ( . vs. . ; p = . ) and lower qol ( . vs. . ; p = . ) than non-dropouts. however, no difference between individuals who dropped or not was found in the interdisciplinary intervention. conclusion: interdisciplinary approach may be more effective to improve clinical features and qol. in addition, this intervention avoids dropout of individuals with worse risk profile concerning adiposity, depression and qol when compared with those having only medical visits. interdisciplinary approach may favor the retention of a subset of individuals at higher risk, which may result in long-term cardiovascular protection. aims: consumption of high fat diet (hfd) leads to accumulation of intramuscular bioactive lipids: long-chain acyl-coa (lcacoa), diacylglycerols (dag) and ceramides (cer) which are implicated in induction of muscle insulin resistance. the aim of this study was to elucidate the role of hfd, myriocin (an inhibitor of ceramide de novo synthesis) and metformin on skeletal muscle lcacoa, dag, cer and acyl-carnitine content and their impact on proteins of insulin pathway. the experiments were performed on male wistar rats: -fed standard rodent chow (control), -fed hfd, -fed hfd treated with myriocin, (hfd/myr) and -fed hfd treated with myriocin and metformin (hfd/myr/met). muscle bioactive lipids were analyzed by lc/ms/ms and plasma glucose and insulin concentration by standard assays. content and phosphorylation of akt and glycogen synthase (gs) was measured by western blot. results: compared to control, all measured lipids were elevated in hfd group. these changes were accompanied by decreased phosphorylation of akt and gs and impaired glucose disposal. myriocin caused a decrease in cer but an increase in the other lipids content as compared to hfd. introducing metformin to hfd/myr group attenuated levels of lipid metabolites known to interfere with insulin signaling (cer, dag, lcacoa) and increased acyl-carnitine content as compared to hfd/myr. in hfd/myr and hfd/myr/met groups insulin-sensitizing effects were accompanied by enhanced akt and gs phosphorylation when compared to hfd. conclusions: simultaneous treatment with myriocin and metformin redistributes fatty acids to β-oxidation which attenuates muscular content of bioactive lipids and improves glucose tolerance by promoting akt phosphorylation. pro-inflammatory state leading to abnormal production of hormones like leptin and adiponectin. the present study was designed to explore endocrine dysfunction of adipose tissue in metabolic syndrome. the study included subjects; metabolic syndrome cases as defined by international diabetes federation and age and sex matched controls. the blood samples were collected for estimation of serum triglycerides, hdl-c, insulin, leptin, adiponectin and fasting plasma glucose. leptin and adiponectin were estimated by elisa and insulin by electrochemiluminescence immunoassay. other biochemical parameters were estimated on clinical chemistry analyzer by standard methods. homa-ir as an index of insulin resistance was calculated from fasting plasma glucose and serum insulin levels. results: serum leptin level was significantly higher in metabolic syndrome patients ( . ae . ng/ml) in comparison to control group ( . ae . ng/ml). serum adiponectin was significantly lower in metabolic syndrome patients ( . ae . lg/ml) in comparison to control group ( . ae . lg/ml) levels. significant difference of homa-ir was between metabolic syndrome cases and controls (p < . ). conclusions: it is concluded that altered endocrine functions of adipocytes are associated with metabolic syndrome and leptin and adiponectin has potential to be incorporated as components of diagnostic criteria of metabolic syndrome. aim: to devise noninvasive method to diagnose nafld. methods: one hundred and eight patients were examined: biochemical blood analysis, endotoxin and nitric oxide in blood, shortchain fat acids (sfa) in faeces, biopsy of liver. patients have been divided into two groups depending on activity of hepatitis: . steatosis; . steatohepatitis, and into three groups according to the therapy: . statin; . probiotic; results: we didn′t revealed direct correlation between biochemical parameters of liver function and heaviness of morphological changes in liver. however patients with steatohepatitis had increased level of endotoxin ( . ae . ) and nitric oxide ( . ae . ) in blood. total quantity of sfa in faeces was also decreased in those patients. there was more effective decrease of lipids, endotoxin and nitric oxide in those patients, who received probiotic in combination with statin. if patient received only probiotic there was not any changes of lipids, but the level of endotoxin and nitric oxide became lower. if nafld progressed in steatohepatitis and there was high level of c-gtp and transaminases we didn′n notice such effective decrease of cholesterol. . the increase level of endotoxin and nitric oxide in blood is the marker of steatohepatitis. . application of statin in combination with probiotic is more effective in achievement of target levels of lipids and decreasing endotoxin and nitric oxide. . if patient has steatohepatitis, effectiveness in the hypolipidemic therapy decreases (in comparison with steatosis), because the metabolism of drugs in liver decrease. methods: one hundred and eight patients with nafld were examined: biochemical blood analysis, endotoxin and no in blood, shortchain fat acids (sfa) in faeces, biopsy of liver (index of steatosis (is) and index of histological activity (iha)). patients have been divided into two groups: . steatosis; . steatohepatitis. results: total quantity of sfa in faeces was decreased in all patients, but there wasn′t difference between i and ii groups. all patients with had increased level of endotoxin ( . ae . ) and nitric oxide ( . ae . ). there was correlation between alt and ggtp with endotoxin and no (ast/endotoxin r = . ; ggtp/endotoxin r = . ; ast/no r = . ; ggtp/no r = . ; p < . ). the biopsy of liver showed all signs of nafld including changes of tiny bilious ductules. we didn′t revealed direct correlation between biochemical parameters of liver function and heaviness of morphological changes in liver (appearance of morphological attributes of steatohepatitis precedes development of cytolytic and cholestatic syndrome). however there was reliable direct correlation between endotoxin and no with histological parameters of nafld (is and iha): is/endotoxin r = . ; iha/endotoxin r = . ; is/no r = . ; iha/no r = . ; p < . . . endotoxin and no may be used in diagnosing of nafld. . increase of level of endotoxin and no in blood in patients with nafld is associated with progression of inflammation in liver. thereby blood analysis for endotoxin and no can be used in diagnosing of nafld progression. . we also can judge about effectiveness of treatment of nafld by the level of endotoxin and no in blood. of this study was to analyze incidence obesity and insulin resistance in patients with fatty liver. the study involved patients with diagnosis non alcoholic fatty liver at the clinical centre pristina. there were analyzed demographic and anthropometric characteristics of the examined patients. of clinical characteristics, there were determined smoking habit, arterial pressure. routine biochemical analyses were carried out by a standard laboratory procedure. homa-ir was used to evaluate insulin resistance. results: in the study group, fatty liver was demonstrated by ultrasound in ( . %) subjects and in the control group there were respondents ( . %) without pathological findings of ultrasound and with the level of p < . . the values of bmi ( . ae . kg/m vs.; p < . ), waist circumference ( . ae . vs. . ae . cm; p < . ) and glucose ( . ae . vs. . ae . mmol/l; p < . ), level of insulin ( . vs. . mu/i; p < . ) and homa-ir ( . vs. . ; p < . ) were significantly higher. conclusions: these results confirm that obesity and insulin resistance are associated with fatty liver infiltration. background and aim: this study was designed to determine the impairment of the skin structure in experimentally-induced diabetes with injection of streptozotocin (stz). material and methods: experimental groups consisted of controls (group , n = ) and diabetes groups (group , n = ). dorsal skin was removed for routine histological tissue procedures. hematoxylene and eosin (he), masson's trichrome and periodic acid schiff (pas) stainings, immunohistochemical connexin (cx ) and type iv collagen stainings were applied. morphometry of epidermal thickness were also determined. results: group revealed decrease in epidermal thickness with disintegration of epithelium and decrease of dermal collagen fibers. stratum spinosum were morphologically abnormal for group . measurements of epidermal thickness revealed statistically significant decrease (p . ). pas staining for group revealed disruption of the basement membrane. epithelial scar formation, deterioration of transformation in the polyhedral cells, degradation of epidermis and decrease in pas staining for vascular structures were observed, whereas the reticular dermis and hair follicles were normal. collagen fiber density in group were found to be prominently decreased in dermis with masson's trichrome staining. evident decrease in immunostaining of cx and type iv collagen were also shown in diabetic group in comparison to the controls. conclusion: diabetes not only induced impairment of the epidermal integrity and deterioration in the epidermis via loss of gap junctions (the most prominent cellular junctional complex), but also caused dramatically negative impact on the dermal collagen content, and integrity of the basement membrane. background and aims: obesity, a major obstacle in the improvement of human health, is associated with an increased risk of development of numerous diseases. on the other hand, plant metabolites showed various bioactivities on affecting food intake, lipase activity, energy expenditure and lipid metabolism that may have potential on preventing body weight gain. therefore, this study aims to discover a new metabolite with anti-obesity efficiency. brief methods: adipocyte differentiation was induced by dexamethasone, -iso-butyl- -methylxanthine and insulin in t -l preadipocyte. in vivo, male c bl/ mice were fed a normal diet (nd), high-fat diet (hfd), a lucidone-supplemented hfd in lower dosage of mg/kg of diet (lsh/l) or in higher dosage of mg/ kg of diet (lsh/h) for weeks. record the changes of body weight and food consumptions. physiological parameters in plasma were determined after sacrificed. epididymal and perirenal adipose tissues were collected for further histological analysis. results: lucidone at mmol/l suppressed adipogenesis in t -l cells by reducing transcription levels of adipogenic genes, including pparg, c/ebpa, lxr-a, lpl, ap , glut and adiponectin. lsh/ h mice showed lowered body and liver weights, decreased food efficiency, and lowered plasma cholesterol, triglyceride, glucose, and insulin levels. dissection of adipose tissue from lucidone-fed mice showed reductions in the average fat-cell size and percentage of large adipocytes. conclusion: these results provided evidence that dietary intake of lucidone alleviates high fat diet-induced obesity in c bl/ mice and reveals the potential of lucidone as a nutraceutical on preventing obesity and consequent metabolic disorders under unhealthy eating habits. introduction and aim: obesity and type diabetes (t d) are accompanied by intramyocellular lipid accumulation which might lead to mitochondrial dysfunction and insulin resistance. our aim was to compare changes in peripheral insulin sensitivity and mitochondrial respiration after a diet-and subsequently a gastric bypass induced weight loss in obese patients with or without t d. materials and methods: sixteen subjects ( m/ f; with (t dm) and (ob) without t d) reported thrice to the lab after an overnight fast: prior to weight loss (a), mo later just prior to operation (b) and mo after operation (c). at each visit tree tests were performed: day : dexa scan for body composition and stationary graded bicycle test for vo max. day : hyperinsulinaemic euglycemic clamp for peripheral insulin sensitivity. prior to the clamp a vastus lateralis muscle biopsy for high resolution respirometry was obtained. respiration protocol is shown in fig. . results: anthropometric, body composition and vo max data are shown in fig. . insulin sensitivity (gir ffm ) and maximally coupled respiration (gmso ) data are shown in fig. . conclusion: in spite of a marked difference in insulin sensitivity, maximally coupled mitochondrial respiration was similar in the two groups. moreover, with marked improvements in t dm insulin sensitivity, due to the massive weight loss, mitochondrial respiration remained unchanged. these results speak against an association of mitochondrial respiratory capacity and insulin resistance in skeletal muscle in obese and t d patients. introduction: increased circulating levels of resistin was proposed as a possible link between obesity and insulin resistance. we investigated if increased resistin expression in adipose tissue affected age-related changes in insulin resistance of peripheral tissues, including brown adipose tissue (bat), and oxidative stress parameters in the spontaneously hypertensive rats (shr). methods: sixteen months old male shrs expressing the mouse resistin gene under control of adipose tissue specific ap promoter (shr-tg) and age matched non-transgenic shrs were used. results: transgenic expression of resistin was associated with impaired glucose tolerance measured during ogtt (auc ae vs. ae mmol/l/ h, p < . ); elevated serum insulin ( . ae . vs. . ae . nmol/l, p < . ) and triacylglycerols ( . ae . vs. . ae . mmol/l, p < . ) levels. shr-tg exhibited lower insulin sensitivity measured as insulin stimulated incorporation of c-glucose into lipids in epididymal adipose tissue ( ae vs. ae nmol gl./g/ h, p < . ) and into skeletal muscle glycogen (p < . ). glucose oxidation in soleus muscle (p < . ), and bat (p < . ) were reduced. shr-tg displayed decreased c-palmitate oxidation to co in bat ( . ae . vs. . ae . nmol/g/ hod, p < . ). in adipose tissue of shr-tg rats was increased concentration of lipid peroxidation products (conjugated dienes and tbars), reduced activity of antioxidant enzymes: superoxide dismutase ( . ae . vs. . ae . u/ mg protein, p < . ) and glutathione peroxidase ( ae vs. ae lmol nadph/min/mg protein, p < . ). conclusion: chronic transgenic expression of resistin gene might contribute to insulin resistance and associated metabolic disorders suggesting possible involvement of reduced bat metabolic activity in age-induced prodibetogenic effect of resistin. examination of patients with type diabetes mellitus (t dm) revealed patients ( . %) with non-alcoholic fatty liver disease (nafld). nafld met more often in the patients with obesity ( . %) and overweight ( . %) and only in . % patients with normal body weight. all the patients had abdominal type of adipose tissue distribution regardless of body weight. in patients with t dm and normal body weight the nafld met more often in women, and in overweight and obesity in men. in the examined patients with t dm and nafld complaints peculiar to dyspepsia and asthenovegetative syndrome prevailed. the average level of hba c corresponded the state of subcompensated carbohydrate exchange ( . %). these patients had marked dyslipidemia with predominance of ii and iib types of hyperlipidemia. cytolytic, cholestatic, mesenchymal-inflammatory syndromes were marked out as well as syndrome of hepatic-cellular insufficiency. increased level of immunoreactive insulin iri ( . ae . ) mu/ml and index of homa ir ( . ae . ) mu/ml testified the presence of expressed insulin resistance in the patients with t dm and nafld. the patients revealed the increase of free fatty acids level ( . ae . ) mmol/l/ml, that meaningfully differed from such indexes in the control group (p < . ) and low level of adiponektin ( . ae . ) mg/ml that confirms their role in development of nafld even for persons with normal body weight after the presence of abdominal type of adipose tissue distribution. study object: diene (dc), triene (tc), oxydien (odc), tetraen (trc) conjugates, malondialdehyde (mda), aspartate aminotransferase (ast), alanine aminotransferase (alt). the study involved patients with type diabetes mellitus and non-alcoholic fatty liver disease (nafld) - men and women among them and diabetes women without nafld. all subjects are representative on age and diabetes duration. correlation analysis has been conducted with the calculation of spierman rank correlation coefficient. study results: the increase of tc and odc levels has been marked in type diabetes men with nafld vs. women -( . ae . ); ( . ae . ) and ( . ae . ); ( . ae . ), respectively, p < . , as well as ast and alt levels -( . ae . ); ( . ae . ) and ( . ae . ); ( . ae . ), respectively, p < . , p < . . the positive correlation of ast, alt with odc and trc has been found among type diabetes women with nafld (r = . , r = . , p < . ) and (r = . , r = . , p < . ) unlike women without nafld -(r = À . ) between ast and trc and (r = . ) between alt and trc. ast, alt are in positive correlation with ct in men (r = . , r = . , p < . ). in type diabetes men with nafld the oxidative stress displays are more clearly seen. it is expressed in increasing of tc and odc combined with ast and alt hyperactivity. trc levels are increased in women group with ast and alt increasing vs. type diabetes women without nafld. the above mentioned can serve as a diagnostic marker of nafld in type diabetes women. i. kara, b. bonardo, f. peiretti umr , inserm, marseille, france gamma secretase and the triggered notch signalling are involved in the regulation of the differentiation/proliferation equilibrium of progenitor cells. gamma secretase consists of four subunits: presenilin or , nicastrin, pen- and aph (stoichiometry : : : ). in humans, there are two aph proteins (aph a and aph b). in rodents there is an additional protein, aph c issued from a duplication of the aph b gene. it has been reported that inhibition of c-secretase improves insulin resistance and stimulates adipogenesis. these data led us to study the impact of obesity in the regulation of the c-secretase composition. expression of c-secretase subunits was measured by quantitative pcr (tissues and cells) and western blot (cells). the expression of aph b is significantly increased in the adipose tissue of obese mice whereas the expression of the other subunits of the c-secretase is not altered. the increased expression of aph b is not observed in muscles and liver of obese mice. the expression of aph b is also increased in visceral adipose tissue of human obese subjects. in addition, the expression of aph b/c increases during adipocyte differentiation of t l cells. in conclusion, the c-secretase composition is specifically altered in hypertrophied adipocytes. this result provides the first evidence of a pathophysiological regulation of aph b/c expression. an approach to knockdown adipocyte expression of aph b/c is in progress. the analysis of the consequences of this manipulation on csecretase activity, notch signalling and the biology of the adipocyte will help assess the importance of the alteration of c-secretase composition during adipocyte differentiation. background and aim: certain legumes and barley kernels may favorably modify metabolic risk parameters in semi-acute studies in healthy subjects. this investigation assessed the medium-term effect of a diet combining specific legume and whole grain barley products on markers associated with the metabolic syndrome (mets) in mature women. design and methods: randomized crossover intervention in women ( - years-old, bmi - , normal fasting glycemia), comparing a diet rich in kernel-based barley products, brown beans and chickpeas (d ) with a control diet (d ) of similar macronutrient composition but lacking legumes and barley. d included g (as eaten)/day legumes, g whole grain barley kernels and g barley kernel bread. both diets followed the nordic nutrition recommendations and provided similar amounts of dietary fiber ( . g/day, d ; . g/ day, d ), with wheat-based products as main fiber supplier in d . each diet was consumed for week under weight-maintenance conditions. blood lipids, glucose, insulin, crp, gamma-glutamyl transferase (ggt) and blood pressure were the measured outcomes. results: both diets decreased serum cholesterol fractions, but d had greater effect (p < . ) on total and ldl-cholesterol (changes from baseline: À % and À %, respectively) than d . d also reduced ggt (À %, p < . ), diastolic blood pressure (À %, p < . ) and the framingham cardiovascular risk estimate (À %, p < . ), while d had no effect. methods: group i (n = )women with ms were examined proinflammatory cytokines polymorphisms, group ii (n = )testing for hereditary and acquired forms of thrombophilia. all subjects had the fetal loss syndrome, fetoplacental insufficiency, severe preeclampsia in previous pregnancies. results: group ipolymorphisms il- β - t/c in . %, il- - g/c-in . %, tumor necrosis factor-a - g/ain . % of cases. in ii group the multigenic defects were verified in % of cases; the feature of multigenic defects is that the g/ g polymorphism of plasminogen activator inhibitor- (pai- ) gene was found in . % of cases, the g/ g phenotype of the gene pai- was verified in . % of cases. the polymorphism in the tissue-type plasminogen activator i/d gene, in the angiotensin-converting enzyme i/d gene, in the fibrinogen g/a gene were found in . %, . %, . % respectively. acquired antiphospholipid antibodies were verified in . % of cases. all women received antithrombotic therapy from the fertile cycle involved low molecular-weight heparin (enoxaparin sodium, daily dose . - . ml), vitamins b, folic acid. pregnancy was achieved in %. there were not recurrent fetal loss, severe pre-eclampsia, placental abruption in the study groups. live births was in all cases. conclusions: we suggest that proinflammatory and thrombophilic status is an important pathogenetic factor of recurrent fetal loss, severe pre-eclampsia and other obstetric complications in women with ms. timely antithrombotic prophylaxis may be a key of successful outcome of pregnancy. the prescription of an individualized rehabilitation program based on the crossover point of substrate utilization (cop) could be particularly relevant in patients with metabolic syndrome (ms). the aim of the study was to examine: . the effects of a week rehabilitation program at an intensity corresponding to cop on the anthropometric characteristics of women with ms, and . these effects after a month follow-up period without supervision. nineteen women with ms ( . ae . years; . ae . kg; bmi = . ae ) performed an indirect calorimetry test to determine their cop and then participated in a supervised rehabilitation program ( min/week at cop on cycle-ergometer over weeks). afterward, they were instructed to continue to practice a physical activity without supervision over months. the target exercise intensity at cop was . ae . % maximal aerobic power. mass, body mass index, waist and hip circumferences, waist-hip ratio, relative fat mass and fat-free mass were significantly decreased whereas energy balance was significantly increased after the rehabilitation program. there were no significant differences at the end vs. months after the rehabilitation program. two months after the rehabilitation program, only both circumferences, waist-hip ratio and energy balance were not significantly different from baseline values. an individualized rehabilitation program over weeks at cop allowed to improve the anthropometric characteristics in women with ms. however, although the energy balance remains unchanged during the month follow-up period, only the effects on circumferences are maintained months after the rehabilitation program. objective: hypoxia contributes to adipose tissue inflammation and fibrotic remodeling in obesity. we have recently shown that longchain n- polyunsaturated fatty acids (pufa) ameliorate adipose tissue inflammation in obese subjects. here we investigated, whether long-chain n- pufa also reduce adipose tissue hypoxia and may prevent adipose tissue remodeling. patients and methods: in a randomized controlled clinical trial we treated severely obese subjects (bmi > kg/m ) with either . g/ day highly purified long-chain n- pufa or control for weeks. at the end of the treatment we sampled visceral and subcutaneous adipose tissue (vat and sat) during elective bariatric surgery. we quantified gene expression of hypoxia and fibrosis markers in tissue specimen by real-time quantitative rt-pcr. statistical analyses were performed by one-way anova. results: adipose tissue gene expression of hif a correlated positively with cd expression, a m macrophage marker and expression of both genes was significantly reduced after n- pufa treatment in sat (p < . ). furthermore, hif a expression correlated negatively with the anti-inflammatory fatty acid index in the treatment group. n- pufa significantly downregulated the pro-fibrotic markers tgfb, mmp and col a in sat. conclusions: mitigation of adipose tissue inflammation by n- pufa is paralleled by the amelioration of hypoxia and prevention of tissue remodeling as estimated by marker gene expression. these data emphasize beneficial effects of high-dose n- pufa in obesity. biochemistry, university of medicine and pharmacy "carol davila", faculty of medicine, university "titu maiorescu", delta hospital, nidnmd "n.c. paulescu," bucharest, romania background and aim: the diabetes "epidemic" nowadays appeared at the same time with the obesity "epidemic", their relationship being a causal one. weight gain cannot be conceived without a good sensitivity to insulin. all three paraoxonases have antioxidant properties. these protect vascular tissues from oxidative damage by modulating the effects of the main actors in the atherosclerotic process, namely the hdl and ldl particles and the macrophage. in this study we aimed to investigate the role of paraoxoanse (pon ) in the relationship between obesity and type diabetes. materials and methods: ten obese patients with type diabetes mellitus were compared with non-diabetic obese subjects. we determined the pon in preadipocytes cells obtained from bariatric interventions and in differentiated adipocytes (day , , , , ) . elisa method was used for leptin and adiponectin measurements. results: the obesity antropometric markers (waist and hip circumference, visceral fat index) were positively correlated with the value for leptin and negatively with the value for adiponectin (p < . ). the intracellular pon tented to be lower with the degree of diferentiation and these was associated with adipokines changes both in serum and cell lysates. conclusion: resuming our data, we presume that pon is present in pre/adipocytes and could be implicated in prevention of type diabetes obesity associated complications. acknowledgements: this work was supported by a grant of the romanian national authority for scientific research, cncs-uefiscdi, project numer pn-ii-id-pce- - - ". dr. lixandru was supported by the postdoctoral program posdru/ / . /s/ , from european social fund. . the effects of a week individualized rehabilitation program (irp) coached at an intensity corresponding to the crossover point of substrate utilization (cop) on hqrol, peak of oxygen uptake (vo peak ) and power out peak (p peak ); . the effects on hqrol after a month follow-up period without coach. nineteen women with metsyn ( . ae . years; . ae . kg) performed a test to exhaustion to estimate the vo peak and p peak , and an indirect calorimetry test to determine their cop used during a irp ( min/week) on cycle-ergometer over weeks. afterward, they were instructed to continue their physical activity without coach over months. vo peak and p peak were increased after the irp (p < . ). hrqol were no different in every domain at the end and months after the irp. only the question about their change of health compared to year ago has improved but it was at the verge of significativity (p = . ). women with metsyn undergoing irp coached at cop improved vo peak and p peak, but showed no improvement in hrqol after a week coached irp nor after the month follow-up period without coach. consequently, physical fitness seems not be associated with self-perceived quality of life in women with metsyn. t.b. domagala , k. kotula-horowitz , r. januszek , m. janczura , j. zagajewski , j. musial micronized fenofibrate ( mg/day) for months. fifty cardiovascular risk male volunteers (mean age years) with no prior myocardial infarction or stroke were enrolled as the controls. brachial fmd and homocysteine levels were measured at baseline and after months. the respective groups also differed in: bmi (p < . ), plasma total (p = . ), hdl cholesterol (p = . ) and triglycerides (p = . ), but not in baseline plasma homocysteine levels ( . ae . vs. . ae . lmol/l; p = ns). at baseline, mean brachial fmd were lower in the subjects with metabolic syndrome ( . ae . % vs. . ae . %; p < . ). in those subjects fenofibrate therapy significantly improved fmd ( . ae . % vs. . ae . %; p < . ) and increased plasma homocysteine levels ( . ae . vs. . ae . lmol/l; p < . ). no such differences were noted in the controls, neither before nor after months. conclusions: fenofibrates improve endothelium-dependent fmd of the brachial artery, irrespective of the simultaneously induced hiperhomocysteinemia. a. picu , l. petcu , d. lixandru , i. stoian , c. cristescu , e. rusu , c. ionescu-tirgoviste nidnmd "n.c. paulescu", biochemistry, university of medicine and pharmacy "carol davila", "titu maiorescu" university, bucharest, romania background and aims: oxidative stress leading to macrophage foam cell formation is the hallmark of the early atherosclerotic lesion. the aim of these study was to assess the relationship between clinical, biochemical and oxidative stress risk factors with obesity in newly diagnosed type diabetes (n-dm). materials and methods: one hundred and forty-five patients with n-dm registered in the nidnmd ambulatory, "n.c.paulescu" and healthy volunteers were included. the n-dm patients were divided into two subgroups according to the bmi (body mass index): group overweight (bmi = . - . kg/m²) and group -obese (bmi ! kg/m²). in circulating monocytes, the ability to produce free radicals vs. their neutralizing capacity was determined by measuring nadph oxidase activity (respiratory burst; rb) and intracellular activity of pon . we also determined the serum leptin and adiponectine by elisa, total antioxidant capacity (teac) and the concentration of non-protein thiols (shneproteic) by spectrophotometric methods. results: in diabetic patients vs. normal subjects, leptin, proinsulin and rb were increased (p < . ), while adiponectin and pon decreased (p < . ). the differences were accentuated in the obese group. the strongest correlation was between proinsulin and leptin (r = . , p < . ) and both contribute for the high cardiovascular risk in type diabetes. our results showed imbalance pro/antioxidant of obese diabetic patients, low pon activity and increased rb being influenced by the degree of obesity. introduction: cardio-protective role of human hdl-associated serum paraoxonase (pon ) is believed to be due, at least partly, to its antioxidative properties. pon activity is genetically determined by major polymorphism q r. brachial flow-mediated dilation (fmd) is a non-invasive physiological measurement used to quantify endothelial dysfunction. fibrates are known to exert hypolipidemic effects, while their effect on pon activity remains unclear. aim: to assess pon activity and fmd in the subjects with metabolic syndrome on fenofibrate treatment. methods: forty male subjects (mean age years) with hipertriglicerydemia, as well as metabolic syndrome, were treated with micronized fenofibrate ( mg/day) for months. pon activity in serum and brachial fmd were measured at baseline and after months. pon q r polymorphism was determined by pcr amplification and restricted digestion; serum pon activity was assayed spectrophotometrically. results there were subjects with qq genotype (group a) and carriers of r allele (group b). at baseline both groups differed in pon activity only ( ae vs. ae u/l; p < . ). fenofibrate treatment reduced pon activity in all subjects, nonetheless significantly in those with qq genotype ( ae vs. ae u/l; p = . ), unlike in the r allele carriers (p = ns). at baseline mean brachial fmd did not differ between groups a and b. fenofibrate therapy significantly improved fmd ( . ae . % vs. . ae . %; p = . ) in group a subjects, unlike group b ( . ae . % vs. . ae . %; p = ns). this study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. treatment of sprague-dawley rats with nicotine ( mg/kg/day) for weeks significantly reduced blood insulin level but had no effect on blood glucose level. both insulin tolerance test and glucose tolerance test demonstrated that nicotine treatment enhanced insulin sensitivity. pretreatment of rats with hexamethonium ( mg/kg/day) to antagonize peripheral nicotinic receptors except for a nicotinic acetylcholine receptor (a -nachr) had no effect on the insulin sensitizing effect of nicotine. however, the insulin sensitizing effect of nicotine was totally abrogated in a -nachr knockout mice, indicating the involvement of a -nachr. further, chronic treatment with pnu- ( . mg/kg/day), a selective a -nachr agonist, significantly enhanced insulin sensitivity not only in normal mice but also in amp-activated kinase-a knockout mice, an animal model of insulin resistance with no sign of inflammation. moreover, pnu- treatment enhanced phosphorylation of signal transducer and activator of transcription (stat ), a molecule involved in regulating insulin signaling, in skeletal muscle, adipose tissue and liver in normal mice. pnu- treatment also improved glucose uptake in c c myotubes and this effect was totally abrogated by stat inhibitor, s i- . all together, these findings indicate that nicotine enhances insulin sensitivity in animals with or without insulin resistance, at least in part via stimulation of a -nachr-stat pathway independent of inflammation. our results not only contribute to the understanding of the pharmacological effects of nicotine, but also identify new therapeutic targets against insulin resistance and type diabetes. calorie restriction (cr) is one of the most reproducible treatments for weight loss and slowing aging. however, how cr induces these alterations is still unclear. this study was designed to understand whether nicotinamide phosphoribosyltransferase (nampt, also known as visfatin) plays a role in the beneficial effects induced by cr using a specific chemical inhibitor of nampt (fk ). sprague-dawley rats were treated for weeks in four groups: ad libitum (al), cr, al + fk and cr + fk groups. al and al + fk animals were allowed unlimited access to standard chow, while the cr and cr + fk animals were restricted to % of the food intake consumed by al and al + fk animals. fk ( mg/kg/ day) was given via drinking water. we found cr upregulated nampt mrna and protein levels in rat skeletal muscle and white adipose tissue. inhibition of nampt did not affect the sirt upregulation by cr but suppressed the cr-induced sirt activity and deacetylation of foxo- . furthermore, inhibition of nampt not only weakened the cr-induced decrease of oxidative stress (ros, superoxide o À˙a nd mda levels), but also greatly abolished the crinduced improvements of anti-oxidative activity (total-sod, gsh and gsh/gssg ratio) and mitochondrial biogenesis. in addition, inhibition of nampt blocked the cr-induced insulin sensitization, akt signaling activation and enos phosphorylation. collectively, our data demonstrate that cr-induced beneficial effects in oxidative stress, mitochondrial biogenesis and insulin sensitivity require functional nampt. background: the anti-diabetic effect of camel milk (cmk) gained increasing recognition in folk medicine and recent clinical and experimental studies. however, the mechanism(s) by which cmk influence the glucose homeostasis is yet unclear. objectives: to investigate the effects of cmk on the blood glucose regulatory mechanisms in control and diabetic animals. materials and methods: experimental diabetes was induced by intrapertional injection of streptozotocin in wistar rats divided into (d & d-cmk) groups. two healthy (c& c-ckm) groups served as control. camel milk ( ml/rat/day) was administered orally to the (d-cmk) and (c-cmk) groups for weeks. the (d) and (c) groups received no treatment. the changes in body weight, blood glucose, glucose tolerance, serum insulin, blood lipids, incretin hormones (glp- and gip), tnf-a, tgf-β , homa-ir and atherogenic index (ai) were investigated. results: the untreated diabetic animals (d-group) exhibited significant hyperglycemia, hyperlipidemia, increased homa-ir and ai, elevated serum icretins, tnf-a and tgf-β levels. this was associated with weight loss and high mortality. camel milk administration to the d-cmk group inhibited the weight loss and mortality and caused significant hypoglycemia, hypolipidemia, insulin secretion, low homa-ir and ai. serum glp- and gip levels show significant elevation but tnf-a and tgf-β were reduced. conclusion: augmented insulin release and decreased insulin resistance together with enhanced incretin hormones release are anticipated to contribute to the anti-diabetic effect of cmk. besides, the peculiar composition of cmk and its anti-inflammatory properties propose it as a valuable adjuvant anti-diabetic therapy. however large-sized clinical studies are still needed. prediabetics reflect dysregulation in glucose homeostasis with obesity is known risk factor in western countries. different degree of obesity contribution toward prediabetics is observed in lean populations. aim: to investigate the role of plasma leptin as a predictor of prediabetics in lean subjects. method: plasma leptin were measured in non-diabetic subjects aged - years old with bmi < . prediabetes (n = ) was defined based on fasting plasma glucose and -h oral glucose tolerance test. plasma leptin were measured in all subjects using commercial elisa kit. binary logistic regressions were used to estimate the age and sex adjusted odds ratio of leptin and other metabolic parameters. results: plasma leptin levels were significantly and positively correlated with bmi, percent total body fat, fasting plasma insulin and blood sugar and homa-ir values. plasma leptin were significantly higher in lean prediabetics ( . ae . ) compared to euglycemic lean subjects ( . ae . ; p < . ). increase in plasma leptin value by one increases the risk of prediabetics with or . ( % ci: . - . ). discussion: in a population of relatively lean and non-diabetic subjects, plasma leptin levels were associated with insulin resistance and prediabetes. furthermore, plasma leptin levels increases risk of prediabetics in non-obese subjects independent of age and sex. our data suggest that leptin as biomarker for screening individuals at high risk for prediabetes in lean population. f. al-zadjali, r. bayoumi latest update from the international diabetes federation shows that the prevalence of type diabetes (t dm) in the arabian gulf countries is among the top worldwide. the rapid increase in t dm prevalence in these countries suggests that psychological and behavioral factors, more than genetic factors, are primarily responsible for this trend. aim: to estimate heritability of plasma levels of adipocytokines in a large isolated arab pedigree. method: blood samples and anthropometric data were obtained from a large arab pedigree of individuals with high level of consanguinity. plasma levels of il- , il- b, leptin, total adiponectin, svcam- were measured using commercial kits. heritability parameters were measured using measured genotype analysis. results: fout hundred and sixty-nine individuals were structured in a large pedigree which consisted of interrelated nuclear families founded by founders. the heritability values were adjusted using age and gender as covariates. percentage of variation of plasma adipocytokines attributed to genetic factors were as following: leptin ( %), total adiponectin ( %), il- b ( %), il- ( %) and svcam- ( %). discussion: adipocytokines play central role in the development of t dm. our data shows high degree of heritability of leptin, il- and svcam- indicating their production is under tight genetic control. furthermore, our heritability values are different from previously reported heritability values of these adipocytkines studied in different ethnic populations. therefore, our results suggests that arab population are distinct and further genetic association and behavioral studies should be conducted for better understanding of the nature of t dm and its increasing trend in middle-east region. results: all treatments were well tolerated and no subjects was withdrawn from the study. compared to the baseline, the group treated with chrome picolinate only experienced a mild but significant decrease in fpg (À . ae . mg/dl). compared to the baseline, the group treated with chrome picolinate-berberine experienced a mild but significant decrease in bmi (À . ae . kg/m ), tc (À . ae . mg/dl), tg (À . ae . mg/dl), non-hdl cholesterol (À . ae . mg/dl), and fpg (À . ae . mg/dl). compared to the baseline, the group treated with chrome picolinate-berberine-banaba experienced a significant reduction in bmi (À . ae . kg/m ), waist circumference (À . ae . cm), sbp (À . ae . mmhg), tc (À . ae . mg/dl), tg (À . ae . mg/dl), ldl-c (À . ae . mg/dl), non-hdl cholesterol (À . ae . mg/dl), fpg (À . ae . mg/dl), insulin (À . ae . mu/l), homa index (À . ae . ) and hba c (À . ae . %), while hdl-c increased (+ . ae . mg/dl). waist circumference, sbp, ldl-c, hdl-c, insulin, homa index and hba c, also significantly improved when compared with other groups. the tested combined nutraceutical appears to significantly improve insulin-sensitivity and a large number of related parameters in subjects with ifg and metabolic syndrome. antioxidative mechanisms prevent human body from the damaging action of free radicals and reactive oxygen species. glutathione and related to it enzyme systems detoxicate h o and hyperoxide and from there, reduced glutathione is a potential marker of oxidative stress level. purpose: to investigete glutathione of erythrocytes in patients with prediabetes (igt and ifg) and type diabetes. matherial and methods: we examined patients with t d and concomitant coronary heart disease (chd) and atherosclerosis (group ), patients with prediabetes (igt and ifg) newly diagnosed and the same co-morbidity (group ) and almost healthy person (group ). examinations included clinical laboratory evaluation, fasting glicose, hba c. total glutathione (gsht) and oxidized glutathione (gssg) were measered by use of glutathione reductase reaction. redox potential (e h ) of glutathione was evaluated by use of nernst equation. results: concentrations of gsht and gsh were greater in group to compare with groups and (by . times, p = . and by . times, p = . respectively). inrease of concentration of gssg in group may change extracellular redox condition. calculation of e h revealed its change to oxidized condition in group to compare with group ( . mv greater) and group ( . mv greater). conclusion: antioxidant defense in red-cells is overactivated during prediabetes (igt and ifg) with concomitant chd and atherosclerosis while in patients with t d was noticed depletion of compensatory mechanisms with increased gssg and e h . reduction in gsh/gssg suggests that intracellular antioxidant is lost; herewith cells become sensitive to oxidative stress. clozapine increases meal size and meal duration, effects similar to the pharmacological blockade or congenital deficiency of cck- (cck- r) receptor. we aimed to investigate the role of cck- r in clozapine-induced weight gain (wg) and insulin sensitivity (is) in cck- r deficient, male otsuka long evans tokushima fatty rats (oletf). long evans tokushima otsuka (leto) rats served as healthy control. animals were orally treated with either clozapine or its vehicle over days. daily food intake was measured by means of metabolic cages. the is was determined by hyperinsulinemic euglycemic glucose clamping (hegc). hypothalamic mrna expression of cck- r and cck- r was measured by real-time pcr, plasma insulin was determined by radioimmunoassay. clozapine failed to induce wg or increment in food intake in either oletf or leto rats. the fasting plasma insulin and blood glucose level was significantly higher in oletf than in leto rats, but clozapine failed to modify these parameters. the glucose infusion rate during the steady state of the hegc was lower in oletf than in leto rats and clozapine did not modify it. the insulin sensitivity index (isi) was lower in oletf rats than in leto and the isi was further decreased by clozapine. the metabolic clearance rate of insulin changed parallel with isi indicating the possible source of the surplus of insulin, which is responsible for the decrement in is. clozapine induced insulin resistance without hyperphagia and wg in male leto and oletf rats. changes in cck- r and cck- r expression were inconsistent with the changes in the isi. clinical biochemistry & immunology, peterborough and stamford nhsft, peterborough, uk the national institute for clinical evidence has published guidelines for the treatment of prediabetes. these stress diet and exercise as shown by the dpp study a decade ago. however, recently published dpp follow-up data show how difficult it is for patients to follow that advice long-term. metformin was also found to be effective and is cheap and generally well-tolerated. this study shows the long-term effectiveness of routine metformin use in patients with igt. all patients attending two rural lipid clinics from who were found to have igt after a standard g ogtt were offered metformin mg bd or given diet and exercise advice if they did not wish medication. metformin was preferred over diet and exercise despite being shown to be inferior in dpp because of the extra cardiovascular benefits shown in ukpds. in , after a mean (range) follow-up of . ( . - . ) years, it was decided to review the data to see if the (off-label) treatment was effective. metformin significantly reduced t dm threefold after years ( % v %). further, it was possible to estimate that metformin could prevent / ever becoming diabetic (p = . ). the effect was due to restoring normoglycymia (fbg < . mmol/l) as the patients' weights and triglyceride levels did not change significantly. patients regularly present to lipidologists with fasting hypertriglyceridaemia. those with igt appear particularly likely to revert to normoglycaemia with metformin. routine use of this inexpensive and well-tolerated drug reduces the lifetime risk of developing t dm by over %. k. salehzadeh, m. shirmohammad zadeh azarbaijan shahid madani university, tabriz, iran as a fermented drink probiotic doogh [ ] can help promote the health of the society. studying crp [ ] changes as an important inflammatory index that predicts coronary-heart diseases such as arteriosclerosis has received attention in medical and nutrition studies. the present study was carried out to study the effects of week drinking different types of dough (probiotic and plain) on the changes of liver crp and other blood factors of male athletes with normal weight. the research sample of this study included healthy male athlete students with equal bmi characteristics that were divided into two testing groups ( each) and were homogenized and randomly divided and went through some exercises. the results of the paired t test showed that drinking plain doogh resulted in significant reduction of blood's urea ( . %) and crp ( . %) and significant increase of hdl ( . %; p < . ). the probiotic doogh also resulted in significant reduction of crp ( . %) and significant increase of hdl ( . %). the comparison of the two groups showed that the only statistically significant difference was in the amount of crp and the reduction effect of probiotic doogh on crp was more compared to the plain doogh (p < . ). also the amount of record changes in the probiotic group (À s) was significantly better than the plain doogh (+ s). background and aims: nutrition has significant effects on human health and diseases. diabetes is a chronic disease that can be affect by nutritional status. therefore, monitoring of nutritional status in these patients is one of the main components of prevention and controlling of complications. therefore, in this study the nutritional status of patients that referred to health center in songhor city was assessed. materials and methods: this descriptiveanalytical study was done on patients with type diabetes ( ae years old) with no insulin therapy. anthropometric mesearments and dietary intake assessment were done. ffq and three recall quessionare were filled with face to face interview. n software were used for analysis. mean ae sd of variables were reported. background: the aetiology of type diabetes and obesity may involve dysregulation of brain appetite control networks. we explored the impact of systemic insulin resistance, common to both conditions, on the effect of meal ingestion on brain responses to food cues. methods: eight insulin resistant (ir, homa -ir . ae . ) and insulin sensitive (is, homa -ir . ae . ) non-obese non-diabetic right-handed men were studied twice, min after consuming ml water (fasted) or kcal mixed meal (fed) in random order. brain responses upon viewing high (hc) and low (lc) calorie food images vs. non-food object (nf) and gaussian blurred (gb) images presented in a block design paradigm were measured using blood oxygenation level dependent functional magnetic resonance imaging. results: the meal reduced hunger (f = . , p = . ) and increased fullness (f = . , p < . ). meal ingestion had no specific impact on responses to lc in either group. in contrast, on viewing hc, there were decreased precuneus responses (vs. gb and nf) and superior temporal gyrus/insula responses to hc (vs. nf) in ir subjects, whilst in is subjects, meal ingestion increased responses to hc (vs. gb) in somatosensory cortex and to all food images vs. gb in putamen/insula, with a trend towards increased dorsolateral prefrontal cortex activity. conclusions: meal ingestion augmented activity in brain regions involved in sensation, interoception and inhibitory control in is subjects during food cue exposure. by diminishing activity in regions involved in imagery and interoception, insulin resistance may influence central appetite control networks to promote further eating after consuming a satiating meal. methods: we examined children with obesity in the endocrinological department of university hospital (minsk) over the year . the number of boys (b) ( . %), mean ae sd age . ae . years; girls (g) ( . %), mean ae sd age . ae years (p = . ). ultrasound (u/s) of the abdominal cavity; the levels of insulin (i); total cholesterol (tc); triglycerides (tg); high-density (hdlc), low-density (ldlc), very low-density (vldlc) lipoprotein cholesterol; atherogenic coefficient (ac); standart oral glucose tolerance test (ogtt) with the calculation of homa-ir and caro indexes; the levels of blood pressure (bp) and body mass index (bmi) were held to all patients. results: sds bmi b was . ae . , g . ae . (p = . ). bp more than th percentile was in ( . %) b and ( %) g (p = . ). the signs of steatohepatosis were determined in ( . %)b, ( %)g. the average levels of tc and tg were in normal limits, gender differenses weren′t noted (p = . ), (p = . ). the concentration of vldlc . ae . mmol/l ( . - . ), . ae . (p = . ). hdlc b and ldlc b didn′t exceed normal limits in boys and girls (p = . ), (p = . ). ac b . ae . ( - ), g . ae . (p = . ). basal and postprandial plasma glucose levels didn′t exceed normal limits regardless of gender (p = . ), (p = . ). the levels of i b . ae . mu/ml ( . - ), g . ae . (p = . ). homa-ir b . ae (< . ), g . ae (p = . ), caro . ae . (> . ), . ae . (p = . ). conclusions: obesity in children was accompanied with arterial hypertension, steatohepatosis and dyslipidemia. the development of insulin resistance with maintaining the basal and postrandial normoglycemia was noted by conducting ogtt in all patients regardless of gender. objective: to evaluate the effect of short-term, moderately high-fat diets on body weight, lipid profile and serum leptin levels. the study was undertaken to create a model with an acute metabolic stress without marked obesity. design: the laboratory mice were fed either a moderately high-fat diet or control diet. body weight, energy intake, body composition, and fasting plasma leptin were compared after and week of dietary treatment. results: after week, abdominal fat mass was % greater in mice fed the high-fat diet than in those fed the control diet (p < . ). however, plasma leptin concentrations did not change much in animals fed the high-fat diet. from to week, animals fed the highfat diet gained weight twice the normal diet group and consumed kj/day more than controls (both p < . ). at week, plasma leptin concentrations per unit abdominal fat mass were % lower in mice fed the high-fat diet (p = . ) and there was a significant negative association between leptin concentrations per unit abdominal fat mass and body weight (r = . , p < . ). conclusions: feeding for weeks moderately high-fat diet is associated with lower than expected circulating leptin concentrations, which correlate with a higher body weight. a high-fat diet may therefore contribute to weight gain by reducing leptin secretion in adipose tissue. the significance of these findings will be discussed. objective: to describe diabetes-related risk factors associated with lower respiratory tract infection (pneumonia) complications among children. methods: we obtained claims data on all hospital admissions to acute care hospitals for children patients with diabetes and pneumonia who were aged - years in bosnia and herzegovina and sarajevo between november , , and november , . these data are checked for accuracy and validity by the pulmologist and diabetologist pediatricians that oversee data collection. in both data sets, we linked diabetic kids patient charts to allow for calculation of previous admission and rehospitalization diabetic kids rates with complications of pneumonia in children. children prescribed more than one antibiotic class contributed to determining the rates of each class. objectives: to examine the extent to which adherence with multiple concomitant healthy lifestyle traits will be associated with the avoidance of the future development of t d. methods: five independent cohorts comprising , men and , women aged - and free of diabetes and cvd at baseline were examined in , , , objective: to investigate the effects of raloxifene on the insulin sensitivity and lipid profile in insulin sensitive and insulin resistant postmenopausal women. study design: this placebo-controlled, double-blind, randomized study involved postmenopausal women aged between and years. all subjects were screened with the insulin resistance homeostasis model assessment (ir-homa) and those patients in the lowest quartile (n = ) were assigned as insulin sensitive and those in the highest quartile as insulin resistant (n = ). patients in both groups received either raloxifene hydrochloride ( mg/day) or a placebo, for a period of weeks. insulin sensitivity, the serum lipid profile, and anthropometric measurements were established before and after therapy. results: women with the highest ir-homa scores were associated with a significantly higher weight, body mass index, waist, and waistto-hip ratio (p < . ). raloxifene significantly reduced the ir-homa scores from . ae . to . ae . (p = . ) and modified the lipid profile in insulin resistant patients when compared to the placebo group and those patients receiving raloxifene in the insulin sensitive group. conclusion: raloxifene reduced insulin resistance and modified the lipid profile in insulin resistant postmenopausal women. diseases, smoking, alcohol consumption, the use of sleeping pills and other potential confounders was also gathered. statistical analyses were done by spss ver. . the average age of the participants was . years old; % was reported current pet ownership. mean hba c was . %, bmi was , and systolic and diastolic blood pressure was and mmhg respectively. pet owners were significantly younger and slightly more overweight; and dog owners were much younger and more overweight than cat owners. in unadjusted analyses, dog owners had a lower rate of taking sleeping tablets than cat owners (p = . %), and dog owners were more likely to be smokers than cat owners (p = . %). however, pet ownership was not associated with hba c, systolic or diastolic blood pressure, bmi, or the prevalence of diabetic complications. conclusions: our results suggest that pet ownership may be associated with insomnia and smoking habits. however, pet ownership is not independently associated with control of diabetes, obesity and prevalence of diabetic complications. objectives: to non-invasively assess the muscular oxygenation response using near-infrared spectroscopy (nirs) and to determine the association between increasing levels of a c and oxygenation response in subjects with type diabetes. materials and methods: forty-five subjects with uncomplicated type diabetes were categorized into two groups: group i (a c < ) and group ii (a c ! ). nirs measurement of vastus lateralis was performed at rest and during a symptom-limited maximal treadmill exercise test to determine muscular oxygenation response. at rest and during peak exercise, deoxygenated hemoglobin (deoxy-hb), oxygenated hemoglobin (oxy-hb) and total hemoglobin (total-hb) were measured with characteristics of light absorptance from nirs. muscle saturation (%) was expressed as the ratio of oxy-hb to total hb volume, an index of tissue de-oxygenation. results: group i subjects (n = with females, . ae . years) were older than subjects in group ii (n = with females, aged . ae . years). the peak vo was comparable between groups. significant lower muscle saturation ( . ae . % vs. . ae . %, p < . ) and more decline (À . ae . % vs. À . ae . %, p < . ) at peak exercise, was noted in group ii. a significant correlation between a c and decline of saturation (r = À . , p < . ) was noted in this study, whereas no other significance were demonstrated in deoxy-hb or oxy-hb. conclusions: this study provided evidence of imbalance of oxygen supply to exercising muscle in asymptomatic and uncomplicated diabetic subjects with elevated a c levels. the insufficient perfusion occurred before vasculopathy and might develop metabolic impairments even myopathy in diabetic subjects with poor glycemic control. study design and method: the lifestyle intervention was conducted as a cluster randomized trial (n = ) in semi-urban setting in sri lanka. the intervention group ( ) received a family centered lifestyle intervention package from family health workers while the control group ( ) received a brief advice from a doctor. duration of the study was -months. results: this study has shown effectiveness in reduction in fasting blood glucose (p < . ), systolic blood pressure (p = . ), diastolic blood pressure (p = . ), weight (p = . ), added sugar (p = . ) and fat consumption (p < . ) while improving physical activity (p < . ) and insulin sensitivity (p < . ) in the intervention group when compared with the control group at follow up assessment. this lifestyle intervention sessions ( ) were carried out by family health workers during their routine house visits. aim: we aimed to compare an experimental type diabetic animal model generated by applying high fat diet combined with single shot of streptozotocin (stz) at mg/kg bw sprague-dawley (sd) rats. methods: we generated and selected rats based on fasting glucose, oral glucose tolerance, and %hba c. once sever type diabetic rats were identified, serum proteins were subjected to d-dige proteomics or comparative d-proteomics after phosphorylation or glycation. results: seven protein targets differentially expressed in severe type diabetic rats (st d) were identified as albumin, vitamin d-binding protein precursor, and transthyretin, respectively. in terms of serum proteins extracted by affinity columns for phosphorylation and glycation, the affinity of phosphorylated protein targets and glycated protein targets were modified under st d condition. results of the ingenuity pathway analysis (ipa) for those targets indicated that antigen presentation, humoral immune response, and inflammatory response are associated networks highly modified in st d group. kidney and liver damages under those st d rats were proposed by ipa and validated by histopathology. polymorphism of patatin-like phospholipase- (pnpla ) has been associated with susceptibility to non-alcoholic fatty liver disease (nafld); whereas genetic studies of nafld in asian indians are not investigated. we investigated the association of polymorphism rs of pnpla with clinical, anthropometric and biochemical profiles in asian indians with nafld. methods: in this case-control study, cases and controls were recruited. abdominal ultrasound, clinical, anthropometry and biochemical profiles were determined. fasting insulin levels and value of homeostasis model assessment of insulin resistance (homa-ir) was determined. polymerase chain reaction and restriction fragment length polymorphism of pnpla gene was performed. the associations of this polymorphism with clinical, anthropometric and biochemical profiles were investigated. results: higher frequency of c/g and g/g genotypes of rs polymorphism was obtained in cases as compared to controls (p = . ), as a consequence frequency of the minor allele g was significantly higher in cases (p = . ). the c/g+g/g genotypes was associated with significantly higher fasting insulin (p = . ), homa-ir (p = . ), alanine transaminase (p = . ) and aspartate transaminase (p = . ). using a multivariate logistic regression model after adjusting for age, sex, body mass index and fasting insulin, subjects with g/g genotype showed higher risk of nafld (or, . , % ci: . - . , p = . ). results: group ; before diet: bg- . ae . mmol/l; months on diet: ae . mmol/l ( . - . mmol/l) months: . ae . mmol/l ( . - . mmol/l); histology: marked necrosis and destruction of bcells on - % islet's surface in islets from ( %); in % not marked necrobiosis or without changes; decreasing of insulin content in b-cells: ig- . ae . (intact- . ae . ); histology: without changes; group : before diet: bg- . ae . mmol/l; months on diet + vitamin b : -bg- . ae . ( . - . mmol/l); months diet + vitamin b : bg- . ae . mmol/l ( . - . mmol/l); histology: partial necro-biosis on - % islet surface in islets from ( %); in other % -without changes; ig- . ae . (intact- . ae . ). conclusions: . months prolonged administration of vitamin b result not marked decreasing of insulin content in b-cells of animals contained on diabetogenic diet and treated by pyridoxin but not protect b-cells of part islets of necrobiosis. aim of this study: to determine the behavior of oxidative stress markers and mitocondrial dysfuncton in non-proliferative diabetic retinopathy. patients and methods: a cross-sectional study was designed with four groups: group : healthy-volunteer subjects. group : patients with mild-non-proliferative diabetic retinopathy (npdr). group : patients with moderate-npdr. group : patients with severe-npdr. serum oxidative stress markers: lipid-peroxidation (lpo measured by malondialdehyde and -hidroxyalkenals), nitric oxide (no metabolites measured by nitrites/nitrates), total antioxidant capacity (tac), activities of antioxidant-scavenger-enzymes in erythrocytes (gpx glutathione-peroxidase and catalase), and mitochondrial dysfunction (expressed in erythrocyte/platelet membrane fluidity and platelet hydrolytic activity of adenosine-thriphosphatase enzyme; atpase). the markers were quantified by colorimetric method. results: patients with npdr had a significant increased serum lpo and no metabolites levels compared to the group . the tac in patients with npdr had a significant decreased compared to the control group. a significant increased in the activities of gpx, catalase and atpase was shown in the experimental groups compared to healthy-volunteer subjects. a significant reduction was shown in membrane fluidity in patients with npdr. the results show that oxidative stress and mitochondrial dysfunction are associated to npdr and its severity. background: weight loss after rous-y gastric bypass (rygb) surgery is associated with alteration of body composition and visceral fat mobilization. we analyzed the amount of fat and fat-free mass reduction in order to identify factors that induce more favorable adiposity change. methods: morbidly obese patients (age = ae years) underwent rygb between september and july . anthropometry, dual-energy x-ray absorptiometry (dexa), computed tomography (ct), life style report, and laboratory test results were registered prior to and year after rygb. results: follow-up rate was . %. dexa demonstrated . ae . of %ffml (percentage of weight lost as fat-free mass) with reduction of % of total fat amount. ct demonstrated higher rate of visceral adipose tissue (vat) reduction rather than subcutaneous adipose tissue with . of %dv/%ds (percentage change in vat vs. sat). patients with diabetes mellitus preoperatively showed more favorable visceral fat reduction (%dv/%ds were . in dm and . in non-dm) even though they lost more fat-free mass. objective: prader-willi syndrome (pws), a genetic disorder characterized by childhood-onset obesity, is reported to have elevated levels of adiponectin. the actions of adiponectin are mediated by adiponectin receptors (adipors) which include adipor and adipor . several cytokines such as adiponectin, tnf-a, and il- , have been known to be involved in insulin sensitivity. methods: thirty pws children (median age . year, boys, girls) who were being receiving growth hormone (gh) therapy and obese children not receiving gh therapy (median age . year, boys, girls) were compared. the relative expression of adiponectin, adipors, several proinflammatory cytokines including tnf-a, and il- measured in peripheral blood mononuclear cells (pbmcs) using real-time pcr. their correlation was analyzed by homeostasis model assessment insulin resistance index (homa-ir). the pws children showed increased expression of adipor (p = . ) and decreased expression of il- (p = . ) compared to the obese children. there was a significant positive correlation between the adipors and tnf-a (adipor vs. tnf-a: r = . , p < . in pws, r = . , p < . in control group; adipor vs. tnf-a: r = . , p < . in obese group). the adipors in the obese group showed significant negative correlation with homa-ir (adipor vs. homa-ir; q = . , p = . , adipor vs. homa-ir; q = . , p < . ). conclusion: in result, inflammatory cytokine expression was closely associated with the expression of the adipors in the pbmcs of both the children with pws and the obese group. adipor expression was highly expressed in the pbmcs of the children with pws. august to november , homeostasis model assessment of insulin resistance (homa-r) were calculated. as a control, subjects were selected, who received oral glucose tolerance test (ogtt) between the same period showing normal glucose tolerance pattern. we used mann-whitney u-test and p-values < . were considered statistically significant. results: there was no significant difference in sex, age ( . ae . vs. . ae . ), bmi ( . ae . vs. . ae . ), hba c ( . ae . vs. . ae . ) and fasting plasma glucose level ( . ae . vs. . ae . ) between the gd group (n = : two males and four females) and control group (n = : one male and five females). the gd group showed significantly higher homa-r than control group ( . ae . vs. . ae . , p < . ). discussion: this study showed that gd patients with normal thyroid function had insulin resistance independent of bmi and hba c. conclusion: gd, even in euthyroid state, is associated with insulin resistance. introduction: it is still remain uninvestigated the correlation of prebiotics and leptin and ghrelin level in frame of inflammatory process in liver. aims and methods: the aim of our study was investigation of nifuroxazide and prebiotic therapy influence on leptin and ghrelin levels in nonalcoholic fatty liver disease patients. determination of leptin and ghrelin (elisa), insulin, il -β, tnf-a were performed in all patients. results: n = patients, female, age ae years, bmi ae kg/m . nafld in %, nash in % and ir in %. leptin was higher in women ( . ae . vs. . ae . ng/dl, p = . ), but ghrelin was similar ( . ae . vs. . ae . pg/ml). leptin positively correlated with bmi (r = . , p = . ) and ghrelin correlated (r = . , p = . ). ghrelin correlated with glycaemia (r = . , p = . ) and correlated to homa (r = . , p = . ). both hormones positively correlated to il -β and tnf-a (ghrelin: r = . , p = . ; r = . , p = . , respectively; leptin: r = . , p = . ; r = , p = . , respectively). prebiotic (npc bic) consumption significantly decreased ghrelin, insulin, il -β, tnf-a level and had no influence on leptin level. the results of liver biopsy (histological examination) and fibromax test showed, that in patients additionally treated by prebiotics, the progress of hepatic fibrosis was significantly slowly, then in cg (fibromax test result: f vs. f ; p < . ). conclusion: our data showed that nifuroxazide and prebiotic therapy decreased inflammation activity and ghrelin level in nafld. cardiology, physiology, medical university of białystok, bialystok, poland aim: ceramide (c) is considered to be an important factor reducing insulin sensitivity. the aim of the present study was to investigate the effect of reduction of the sphingolipid synthesis in the solid tissues on the level of c, and other bioactive sphingolipids, namely sphingosine- -pohosphate (s p) sphingosine (sp), sphinganine (sa) and sphinganine- -phosphate (sa p) in different blood compartments. the experiments were carried out on three groups of male wistar rats, - g of body weight fed ad libitum on a commercially available diet: (i) control, (ii)treated with myriocin (an inhibitor of sphingolipid de novo synthesis) and (iii) treated with nicotinic acid (it reduces the level of plasma free fatty acids). the level of the above mentioned bioactive sphingolipis was determined with the use of mass spectrometry. results: both treatments reduced profoundly the level of each of the examined compounds in the plasma. treatment with nicotinic acid did not affect the level of either compound in erythrocytes but reduced it to a great extend in the platelets. treatment with myriocin reduced the level of each compound, with the exception of sh, in erythrocytes. the compound reduced the level of each compound in the platelets to the level comparable to nicotinic acid. . the level of the examined sphingolipids in the plasma, erythrocytes and platelets depends thoroughly on their supply from solid tissues. . short-term reduction in the plasma free fatty acids level very efficiently reduces the level of bioactive sphingolipids in different blood compartments. background: maternal nutrition plays major role in fetal growth and development. low birth weight and impaired early postnatal growth predispose the offspring to an increased risk for future chronic diseases such as metabolic syndrome. stunting in south african children has previously been documented. the study aimed to investigate effects of maternal nutrition on fetal and early postnatal growth in the population of black urban pregnant south african women, employing ffq, ultrasound and anthropometry measurements. results: based on the z-scores (at birth, weeks and month), babies in the current study were born lighter (À . ) and shorter (À . ) with larger head circumference (+ . ) in comparison with the who child growth standards. the z-scores for both the weight and the lengthfor-age decreased after birth with subsequent increase at months, being significant for length (À . , p = . ) after birth and for weight (+ . , p < . ) at months. maternal intake of polyunsaturated fat in early pregnancy and of total protein in late pregnancy were found associated with the fetal head-to-abdomen circumference (β = À . , p = . and β = À . , p < . respectively) and with the lengthfor-age z-score at weeks (β = . , p = . and β = . , p = . respectively). early plant protein intake significantly correlated with fetal growth rate (β = . , p = . ). conclusion: low maternal pregnancy intake of protein, namely of plant protein, and of polyunsaturated fat affected fetal linear growth, and resulted in a possible "brain sparing effect" in fetus. maternal dietary manipulation during pregnancy may therefore affect fetal and postnatal growth and thus modulate the risk of chronic disease later in life. aims and methods: to assess the efficacy of hb in cp patients in a two centre randomised, double-blind, placebo-controlled, crossover trial. one hundred and twenty-six patients with chronic pancreatitis were exposed to screening blood tests and test of elastase in stool before randomization to placebo or hb (buscopan, boehringer ingelheim) for weeks. all patients followed the basic treatment scheme include dietary and physical regimen. drug effect was optimized by dose titration during weeks - starting at mg daily, increasing (max mg t.d.s) or decreasing as required. methods: brown beans, or white wheat bread (wwb, reference product) were provided as evening meals to healthy young adults in a randomized crossover design. markers of glucose-and appetite regulation, glp- , and markers of inflammation were measured at a following standardized breakfast, i.e. - h after the evening meals. colonic fermentation activity was estimated from measurement of plasma short chain fatty acids (scfa) and breath hydrogen (h ) excretion. results: an evening meal of brown beans, in comparison with wwb, lowered blood glucose (À %, p < . )-and insulin (À %, p < . ) responses, increased satiety hormones (pyy %, p < . ), suppressed hunger hormones (ghrelin: À %, p < . ), and hunger sensations (À %, p = . ), increased glp- ( . %, p < . ) and suppressed inflammatory markers (il- À %, and il- À . %, p < . ) at a subsequent standardized breakfast. breath h ( %, p < . ) and plasma scfa (propionate % and isobutyrate %, p < . ) were significantly increased after brown beans. results: the present study revealed significantly lower levels of adiponectin in diabetic children compared to the controls ( . ae . vs. . ae . lg/ml). it also showed significantly increased carotid intima media thickness (cimt) in diabetic children compared to the control group ( . ae . vs. . ae . mm). there was also positive correlation between the mean cimt and age of the patient, age of onset of diabetes mellitus, hba c, and bmi measurements in diabetic children. there was negative correlation between mean cimt and adiponectin level. conclusions: subclinical microvascular disease in type diabetes mellitus begins early in diabetic children, which emphasize the importance of early detection and control of vascular risks in diabetic children. the study also suggests that adiponectin may prove to be useful marker of cardiovascular risks, and potential therapeutic target for risk prevention in diabetics. in overweight and obese individuals ( f/ m; age ae years, bmi = ae kg/m ). an intra-venous glucose tolerance test, hyperinsulinaemic-euglycaemic clamp and circulating markers relevant to age signalling were performed before and after each diet. results: the high age diet was fivefold higher in age content than the low age diet. the high age diet reduced insulin sensitivity by À . mg/kg/min ( % ci, À . to À . ; p = . ) while the low age diet improved insulin sensitivity by + . mg/kg/min (+ . to + . ; p = . ). the overall change in insulin sensitivity was . mg/ kg/min ( . - . , p = . ). the change insulin secretion was correlated inversely with the change in plasma age (cml) concentration (r = À . , p = . ). to investigate the level of transforming growth factor (tgfbl) and basic fibroblast growth factor (bfgf), non-specific markers of inflammation: interleukin- (il- ), tumor necrosis factor-a (tnf-a) in patients with coronary heart disease (chd) depending on the presence of dm . the study involved people: one group À patients with chd without carbohydrate metabolism disorders, two group - patients with dm and chd. blood samples were taken from the cubital vein and the aorta during coronary angiography. . )], as in arterial and venous blood in the presence of chd and dm (p < . ). . availability dm in patients with chd was associated with significant increase in the level of tgfb , il- . these observation reflect the effect of chronic hyperglycemia on the restructuring of the connective tissue and the vascular wall. . tgfb direct correlation with lipid markers confirms the relationship of connective tissue disorders and lipid metabolism in the pathogenesis of atherosclerosis. obesity can be induced with high fat diets (hfd) and is associated with inflammation in white adipose tissue (wat) and liver. the factors that control the early metabolic responses to hfd and that trigger inflammatory gene expression are only poorly understood. a time-resolved analysis of differentially expressed genes in expanding adipose tissue of mice ( weeks hfd feeding) identified specific clusters of lipid metabolism-related genes and inflammation-related genes with similar time expression profiles. subsequent promoter analysis of the clustered genes revealed that specific master regulators (among which fos, esr , hnf a, jun, ppara, pparg, nr h /lxrb, nfkb, srebf and , sfpi , smad , sp ) orchestrate metabolic adaptations and early inflammatory responses in wat. some of these transcription factors (esr , jun, fos, pparg, sp ) have a dual role and regulate the adjustment of lipid metabolism as well as expression of inflammatory genes such as cxcl /kc, ccl /rantes, complement factors, asc, granzyme a ccl /rantes, ccl , ccl /mcp . subsequent analysis of corresponding livers revealed comparable molecular responses on the level of transcription factors. more specifically, many master regulators identified in wat were also involved in the liver response to hfd as demonstrated by analysis of hepatic target gene expression in conjunction with transcription factor binding activity analysis. our findings support the view that metabolic and inflammatory processes are interlinked in wat and liver, and that responses to hfd are controlled in a similar way on the transcription factor level. distortions of the mechanisms which control metabolic homeostasis in these organs may thus also affect their inflammatory tone. aim: to investigate the effects of iptakalim, a novel sur b/kir . type atp-sensitive potassium channel opener, on endothelial dysfunction induced by insulin resistance (ir) and to determine whether iptakalim improved ir associated with hypertension in fructose-fed rats (ffrs) and spontaneously hypertensive rats (shrs). methods: the levels of endothelial vasoactive mediators and enos protein expression were determined usingelisas or western blot. in both ffrs and shrs, hyperinsulinemic-euglycemic clamp was used to evaluate ir states. . cultured human umbilical vein endothelial cells (huvecs) incubated with the pi -kinase inhibitor wortmannin ( nmol/l) and insulin ( nmol/l) induced endothelial dysfunction characterized by reduced release of no and expression of enos protein, and increased production of et- . pretreatment with iptakalim ( . - lmol/l) could potently prevent the endothelial dysfunction by increasing no production and inhibiting et- release. . in ffrs, the levels of sbp, fasting plasma glucose and insulin were elevated, whereas the glucose infusion rate (gir) and insulin sensitive index (isi) were significantly decreased, and the endothelium-dependent vascular relaxation response to ach was also impaired. these changes could be prevented by administration of iptakalim for weeks. the imbalance between serum no and et- was also ameliorated by iptakalim. . in - month-old shrs (ir was established at the age of months), oral administration of iptakalim for weeks significantly ameliorated hypertension and increased the gir to the normal level. conclusion: iptakalim could protect against ir-induced endothelial dysfunction, and ameliorate ir associated with hypertension, via restoring the balance between no and et- signaling. m. ste z pie n , a. ste z pie n , r.n. wlazeł , m. paradowski , m. banach , j. rysz material and methods: patients (f , m ) were divided according to bmi into three groups: a-obesity i (n = ); b-obesity ii (n = ) and c-obesity iii (n = ) and into other four groups: females and males and patients treated with statins or fibrates (n = ) or untreated (n = ). results: leptin was significantly higher in group c compared to group a and b [ . ( . - . ) vs. . ( . - . ) ng/ml, p < . and vs. . ( . - . ) ng/ml, p < . respectively]; hs-crp were higher in group c than in group a [ . ( . - . ) vs. . ( . - . ) mg/ l, p < . ]. adiponectin and leptin were higher in females [ . ( . - . ) vs. . ( . - . ), p < . and . ( . - . ) vs. . ( . - . ), p < . , respectively]. resistin, hs-crp and il- were higher in untreated patients' group [ . ( . - . ) vs. . ( . - . ) ng/ ml, p < . ; . ( . - . ) vs. . ( . - . ) mg/l, p < . and . ( . - . ) vs. . ( . - . ) pg/ml, p < . respectively]. leptin positively correlated with hs-crp in the whole population (r = . , p < . ), in treated patients' group (r = . , p < . ) and with tnf-a in group c (r = . , p = . ). conclusions: leptin may be associated with chronic inflammation in obese hypertensive patients. serum leptin and adiponectin levels are sex dependent. hypolipemic treatment has impact on chronic inflammation and resistin. lean body mass in genetically obese (ob/ob) or anorectic/cachectic subjects is severely reduced. similar outcomes of two different pathological states prompted us to wonder if leptin, adipokine well known from its control of appetite interacts with myogenesis. apparently, recombinant leptin ( ng/ml) stimulated dna synthesis in mononuclear myoblasts together with the increase of t /y p-erk / protein expression levels. additionally, leptin reduced cell viability and muscle fiber formation from c c mouse myoblasts. detailed short-and long-term examination with the use of metabolic inhibitors revealed that both jak/stat and mek/mapk but not pi -k/akt/gsk- beta signaling pathways were stimulated by leptin, and that stat (y p-stat ) and mek (t /y p-erk / ) control these effects. in turn, insulin promoted pi -k-dependent phosphorylation of akt (s ) and gsk- beta (s ) and insulin overruled leptin-dependent inhibition of myogenic differentiation in pi -k-dependent manner. gsk- beta might play dual role in muscle development. insulin-induced effect on gsk- beta (s p-gsk- beta) facilitated myotube formation. in contrast, leptin through mekdependent manner led to gsk- beta phosphorylation (y p-gsk- beta) with resultant retardation of myoblast fusion. in summary, to some extent opposite effects of insulin and leptin on skeletal muscle development emphasize the importance of intercellular signaling between adipose tissue and skeletal muscle. insulin and leptin determine how muscle mass is gained or lost, respectively. objective: obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. however, whether macrophage infiltration directly influences human metabolism is unclear. the aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. methods: expression of macrophage markers in adipose tissue was analyzed by dna microarrays in the sos sib pair study and in patients with type diabetes and a bmi-matched healthy control group. results: the expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. after adjustment for bmi, the expression remained associated with insulin sensitivity, serum levels of insulin, c-peptide, high density lipoprotein cholesterol (hdl-cholesterol) and triglycerides. in addition, the expression of most macrophage markers was significantly increased in patients with type diabetes compared to the control group. conclusion: our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of bmi. this indicate that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia. hp gene has been demonstrated to be a major determinant of susceptibility to cvd and in the development and progression of dn. hp allele is defective in its ability to protect against oxidative stress cvd and dn. we decide to assess the intracellular localization of iron in the pctcells and its potential toxicity in the development and progression of dn. methods: wild type c b / mice have only an hp allele. we genetically engineered a murine hp allele and inderted it in the murine hp locus by homologous recombinatiobn. we induced dm, by stz for days, at weeks of age we assessed lysosomal membrane integrity, redox-active iron in kidney lysosomes. . increased iron-rich deposits in lysosomes of pct cells in hp - dm vs. hp - dm ( ae % of all lysosomes) compared with hp - dm mice ( ae % of all lysosomes, p < . ). . intralysosomal redox-active iron concentrations are markedly increased in hp - dm mouse kidneys lysosomes of hp - dm mice ( . ae . lmol/l) as compared with those from hp - dm mice ( . ae . lmol/l, p = . ). lysosomal membrane lipid peroxides are increased in hp - dm proximal tubule cell (p < . ). vitamin e supplementation resulted in a % reduction in lysosomal redox-active iron in hp - dm mice (p < . ). conclusion: a novel mechanism whereby the hp genotype may predispose to renal injury in the setting of dm via increased iron deposition in the lysosomes of pct. purpose: we aimed to use other less hazardous route of insulin injection to prevent pharmacokinetic problems of sc insulin and find out response categories in diabetics and prediabetic patients. besides, fbs and hba c are markers for treatment evaluation; we wondered whether aitt could be a marker of residual pancreatic activity regeneration or decelerating progression of type ii diabetes. methods: five hundred diabetic and patients with impaired glucose tolerance were enrolled to this trial. three hours after breakfast they receive - unit equivalents of insulin into the external auditory cannel. blood glucose level was measured every min for h. this was repeated months later in both groups; while prediabetic patients received some sorts of therapy while the other patients remained on their previous lifestyle. auc and best fit curve were evaluated by partial mathematical integration. results: six different prototypic curves were extrapolated from diabetic patients with the possibility of excellent theoretic explanations about etiology and multifactoriality, lifestyle change, drug(s) of choice and prognosis. parallel to this prediabetic patients showed comparable curves. the area under curve in treated prediabetics showed a small but significant reduction compared to untreated ( vs. , p = . ). conclusions: as shown elsewhere the area under curve after an auditory insulin tolerance test is a nice marker in diabetes response evaluation and prognosis and an excellent marker for progression to diabetes and effectiveness of treatment in prediabetics (< compared to > ). introduction: type ii dm is generally regarded as a progressive disease with control of bs becoming more difficult with time. we wondered whether optimal therapy with "mega-treatments" that can let the pancreas rest could reverse the disease. materials and methods: thirty five patients received optimal doses of insulin through the auditory channel for months. contributing factors such as obesity, anxiety, h. pylori infection and reduced physical activity were treated appropriately. at beginning and every month they were evaluated by way of auditory insulin tolerance test after h of drug vacation. the general appearance of the curve, the partial integration of it and the overall area under curve were compared monthly. results: auc declined from a mean of - from first to sixth month meaning reduced insulin resistance (p < . ). this decline was steady during the whole months and minor variations in different patients were not significant. with mathematical calculation it seems very unlikely that this decline becomes asymptotic so that on extension of the curve for - years at least % of the patients eventually fall into the nondiabetic range with auc under . (p < . ) although different definitions exist for dm, auditory insulin tolerance test might be functionally more illuminating. these results are in concordance with available literature that denotes early aggressive treatment might be better. we add to this notion that early aggressive treatment can possibly reverse type ii diabetes. physiology, universidad de guadalajara, guadalajara, mexico background: c-reactive protein (crp) is an acute stage protein whose serum levels become raise by infection or because an undergoing metabolism disruption. our group has found crp variable serum levels in hypertensive patients that course with obesity and dyslipidaemia. the crp polymorphism rs g>a has been associated to lowered crp serum levels in autoimmune diseases. the role of c-reactive protein (crp), a marker and mediator of inflammation, in the pathogenesis of metabolic syndrome and its complications such as non-alcoholic fatty liver disease (nafld) remains to be elucidate. in this study we investigated whether increased levels of human crp itself can promote increase of glucose and lipid metabolism disorders associated with metabolic syndrome. materials and methods: spontaneously hypertensive rats (shr) with transgenic expression of human crp gene under apolipoprotein e promoter (shr-tg) in age -year and age matched non-transgenic shr controls were used. both groups were fed a high fructose diet ( % cal fructose) for weeks. parameters of insulin resistance and oxidative stress were measured by commercially available kits. results: transgenic expression of crp was associated with significant increase of serum triacylglycerols ( . ae . vs. . ae . mmol/l, p < . ) and insulin levels (p < . ), markedly decrease in insulin stimulated c-glucose incorporation into muscle glycogen ( ae vs. ae nmol/g/ h, p < . ), reduced serum adiponectin ( . ae . vs. . ae . mmol/l, p < . ), and microalbuminuria (p < . ). transgenic expression of crp was associated with increased liver triglyceride concentrations ( . ae . vs. . ae . lmol/g, p < . ), decreased liver glutathione peroxidase activity (p < . ) and reduced glutathione concentration (p < . ). liver lipidperoxidation were elevated in shr-tg rats: tbars (p < . ). conclusion: overexpression of human crp induced insulin resistance, oxidative stress and liver steatosis in shr rats. these finding indicate that chronically inflammation might directly contribute to the pathogenesis of metabolic syndrome and nafld. one of the most topical issues of modern pediatrics is obesity in children and adolescents, which has a tendency to doubling every three decades in almost all countries. the aim of our research was to investigate the fatty acid composition of the blood in children with obesity. patients and method: we investigated children aged from to years, divided into two groups: group i - children ( % boys and % girls) who are overweight or obese (bmi . ae . kg/ m ), group ii - persons ( % boys and % girls) with normal body weight (bmi . ae . kg/m ). research methods: quantitation of omega- and omega- polyunsaturated fatty acids, determination of the total amount of fatty acids, the total content of eicosapentaenoic and docosahexaenoic acids by gas chromatography with mass selective detection and determination of the omega- index (the ratio of the sum of eicosapentaenoic and docosahexaenoic acids to total content of fatty acids in %). results: there was a direct correlation between the value of bmi and the increasing of omega- index and the omega- pufas in children with obesity, while for the children with normal body weight the connection of bmi with the change of the fatty acid composition of blood was not obtained. thus changes of the quantitative and qualitative fatty acid composition of blood in obesity children and adolescents had multidirectional nature and require further dynamic study. a. kopp, a. schmid, m. mü ller, a. schä ffler internal medicine i, university hospital regensburg, regensburg, germany introduction: proteins secreted by adipocytes (adipokines) play an important role in the pathophysiology of type diabetes mellitus and the associated chronic and low-grade state of inflammation. it was the aim to characterize the anti-inflammatory potential of the new adipokine, c q/tnf-related protein- (ctrp- ), which shows structural homologies to the pleiotropic adipokine adiponectin. in earlier studies, recombinant ctrp- has been shown to inhibit lps and lauric acid induced release of pro-inflammatory cytokines and chemokines dose-dependently in monocytes and adipocytes. methods: for in vivo analysis, male c bl/ mice were treated by intraperitoneal lps administration for h. anti-inflammatory effects were tested by pre-treatment ( min) with ctrp- . after killing, epididymal adipose tissue was collected for cytokine mrna expression analysis (real-time rt-pcr) and blood for measurements of circulating cytokine levels (elisa). the anti-inflammatory potential previously found in vitro is also seen in lps-treated c bl/ mice. animals pre-treated with ctrp- have lower levels of inflammatory cytokines such as interleukin- (il- ) and macrophage inflammatory protein- (mip- ). furthermore, mrna expression of il- and mip- in the epididymal adipose tissue is significantly reduced by ctrp- . conclusion: ctrp- acts anti-inflammatory in cells and tissues that are involved in obesity and type diabetes mellitus. therefore, it might be an interesting drug target in treating obesity-related chronic inflammation. objective: the aim of the study was to assess the burden of some metabolic syndrome (ms) risk factors in polish adolescents from two less-urbanized regions as well as the relationship between abdominal obesity, dyslipidemia and hypertension incidence. the study involved adolescents aged - . all subjects lived in two less-urbanized regions of poland (small towns and villages in the central and north-eastern regions). the concentration in blood of triglycerides (tg) and hdl-cholesterol (hdl-c), as well as systolic blood pressure (sbp) and waist-to-height ratio (whtr) were determined. using logistics regression, an odds ratio (or) of the incidence of high whtr ( ! percentiles), high tg ( ! mg/dl), high spb (> percentiles) and low hdl-c (boys: < mg/dl; girls: < mg/dl) was calculated. results: high whtr was found in % of adolescents, high tg in %, high spb in % and low hdl-c in %. adolescents with abdominal obesity (whtr ! percentiles) had an or rated as high spb at . ( % ci = . - . ; p < . ), an or rated as high tg at . ( % ci = . - . ; p > . ) and an or rated as low hdl-c at . ( % ci = . - . ; p > . ) in comparison to adolescents with normal whtr (between and percentiles). adolescents from north-eastern poland had an or rated as high spb at . ( % ci = . - . ; p < . ) and an or rated as high tg at . ( % ci = . - . ; p < . ) in comparison with the central region (or = . ). conclusions: dyslipidemia and hypertension were the main metabolic syndrome risk factors in polish adolescents from less-urbanized regions, especially in central poland. the risk of hypertension rose over times in adolescents with abdominal obesity. objective and aims: as employment has become more sedentary in nature, there is a potential for more working individuals to be at risk of developing the metabolic syndrome (mets). physical activity (pa) is recommended for prevention of such chronic conditions. this study investigates self-reported pa and presence of mets in the workplace as part of the established "prosiect sir gâr" initiative in south wales, uk. methods: two hundred and twenty-one male steel workers (sw) and male local health board (lhb) employees were screened and their data analysed. anthropometric data, blood pressure and self-reported physical activity (gppaq) were all recorded alongside obtained blood samples which were subsequently analysed for high-density-lipoprotein cholesterol (hdl-c). presence of the mets was determined based on the following idf criteria: central obesity (waist circumference: ! cm), reduced hdl-c levels (< . mmol/l) and either systolic ( ! mmhg) or diastolic ( ! mmhg) hypertension. results: the proportion of males diagnosed with mets was comparable between worksites (sw: . % vs. lhb: . %; p = . ) despite the sw reporting being more physically "active" or "moderately active" than their lhb counterparts ( . % vs. . %; p < . ). central obesity, reduced hdl-c levels and diastolic hypertension were comparable between worksites (p > . ), although systolic hypertension was higher amongst lhb employees ( . % vs. . %; p < . ). however, more sw were found to be clinically obese ( . % vs. . %; p = . ). introduction: diabetes mellitus is often a silent disease and its prevalence is increasing rapidly worldwide. nonalcoholic steatohepatitis is certainly the less estimated complication of diabetes in frequency and severity. the aim of our study was to evaluate the prevalence of steatohepatitis and to identify its clinical and biological risk factors. materials and methods: the prospective transversal study was comparative between type diabetics (group ) and healthy people (group ) with no chronic hepatopatic diseases, no alcoholism and no intake of hepatotoxic drugs. all have benefit from a clinical exam, biological assay and abdominal echography seeking for steatohepatitis. results: group has statistically a higher frequency of android obesity, insulin resistance, steatohepatitis, high blood pressure, hypertriglyceridemia, chronic inflammation and silent myocardial ischemia in comparison with group . the steatohepatitis was present in % of patients vs. . % of healthy people; p < . . also, patients from group with steatohepatitis (group a) had a body mass index (bmi), waist circumference, a percentage of fat mass, a level of triglycerides, of alanine aminotransferase (alat) higher than diabetics without steatohepatitis (group b), with a risk of metabolic syndrome multiplied by three. with multivariate analysis, we found that in group , alat and bmi were directly associated to steaohepatitis. our study notifies the frequency of steatohepatitis in diabetics. it could be prevented and treated by loss of weight and regular physical activity in order to reduce insulin resistance. objectives: vascular dysfunction and complications are the major cause of mortality in diabetic patients. arterial stiffness has been known as a useful predictor of atherosclerosis and lipoprotein level is one of major risk factors of atherosclerosis. to investigate the association of lipoprotein level with arterial stiffness, we studied the vascular characteristics of patients with diabetes. methods: fifty patients (male:female = : , mean age . ae . years), with diabetes and without coronary artery disease, were enrolled and evaluated. all patients have been taking angiotensin receptor blocker or angiotensin converting enzyme inhibitor. arterial stiffness was assessed by measuring the carotid-radial pulse wave velocity (pwv). the cardiovascular risk factors, including body mass index, lipid profile, pulse pressure, c-reactive protein, flow-mediated vasodilatation (fmd) were also measured. the pwv was significantly higher in patients with metabolic syndrome than those without metabolic syndrome ( ae vs. ae cm/s, p = . ) in diabetic patients. multivariate analysis revealed that hdl cholesterol level, body mass index and metabolic syndrome were highly associated with pwv (p = . ). pulse pressure, crp, hdl cholesterol level and metabolic syndrome were significantly associated with fmd. conclusion: in diabetic patients, metabolic syndrome and hdl cholesterol level were highly associated with arterial stiffness and fmd as in non-diabetic patients. objective: our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner. research design and methods: obese women (bmi . ae . kg/m ) with metabolic syndrome were randomized into two isocaloric (~ kcal) weight loss groups, a breakfast (bf; kcal breakfast, kcal lunch, kcal dinner) or a dinner (d) group ( kcal breakfast, kcal lunch, kcal dinner) for weeks. anthropometric measurements, oral glucose tolerance test (ogtt) and meal tests were performed. the bf group showed greater weight loss (À . ae . vs. À . ae . kg) and waist circumference reduction (À . ae . vs. À . ae . cm) compared with the d group. although fasting glucose, insulin and ghrelin were reduced in both groups, fasting glucose, insulin and homa-ir decreased significantly to a greater extent in the bf group. mean triglyceride levels decreased by . % in the bf group, but increased by . % in the d group. after ogtt, the extent of reduction of aucglucose and aucinsulin was greater in the bf (À % and À %, respectively) compared with the d group (À % and À %, respectively). in response to meal challenges, the overall daily aucglucose aucinsulin, aucghrelin and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the bf group. conclusions: an isocaloric diet with switched caloric intake during breakfast or dinner differentially influences weight loss and metabolism. high-calorie breakfast with reduced intake at dinner might be a useful alternative for the management of obesity and metabolic syndrome. centre for biomedical sciences, cardiff metropolitan university, cardiff, uk introduction: we have reported that exercise alters markers of monocyte/macrophage polarisation in peripheral polymorphonuclear cells, decreasing the m :m marker ratio. since the m phenotype is considered "anti-atherosclerotic", this may be beneficial in reducing cardiovascular disease risk. this study aimed to determine whether exercise specifically promotes m marker expression in purified monocytes, and to elucidate the molecular mechanisms involved in this process. methods: twenty-six healthy, sedentary individuals ( ae years) participated in a low-intensity exercise programme (walking, min, thrice weekly for weeks). peripheral monocytes were isolated using magnetic immuno-separation, and gene expression was determined by rt-pcr. serum lipids, insulin and glucose levels were measured by standard biochemical methods. the presence of serum pparc ligands was determined by gene reporter assay. results: during the -week exercise programme, pparc ligand generation and cox- gene expression were increased [ . ae . -and . ae . -fold, respectively (p < . )]. similarly, pparc-dependent genes (e.g. cd ) and m marker (e.g. dectin- ) expression increased ( . ae . -(p < . ) and . ae . -fold (p < . ), respectively), while exercise-associated increases in pro-inflammatory m markers were blunted [e.g. mcp- . ae . -fold (p < . conclusion: low-intensity exercise may prime monocytes for differentiation into m -polarised macrophages (possibly via pparcdependent events) and contributes to improved insulin sensitivity. this data supports exercise prescription for the prevention and management of inflammatory-linked diseases such as atherosclerosis and diabetes. quantify and determine possible differences and their correlation with plasma leptin and ghrelin levels. for this study, male rats were underwent a case control study. the fecal bacteria composition was investigated by pcr-denaturing gradient gel electrophoresis and realtime qpcr. in restricted eaters, we have found a significant increase in the number of proteobacteria, bacteroides, clostridium, enteroccoco and prevotella and a significant decrease in the quantities of actinobacteria, firmicutes, bacteroidetes, b. coccoides-e. rectale group, lactobacillus and bifidobacterium with respect to unrestricted eaters. we also found a significant positive correlation between the quantity of bifidobacterium and lactobacillus and plasma leptin levels, and a significant and negative correlation among the number of clostridium, bacteroides and prevotella and plasma leptin levels in all the experimental groups. furthermore, plasma ghrelin levels were negatively correlated with the quantity of bifidobacterium, lactobacillus and b. coccoides-eubacterium rectale group and positively correlated with the number of bacteroides and prevotella. in conclusion, nutritional status and physical activity may have an impact on the gut microbiota composition affecting the diversity and similarity. the significant increase in the quantity of lactic acidproducing bacteria and butyrate-producing bacteria that would also implied an increase in their bacterial metabolites in the exercise rats without dietary restriction could be responsible of the plasma ghrelin levels decrease found in these rats which affect the food intake and the body weight. the aim of this study was to evaluate the relation between weight gain classified according to iom recommendations and macronutrient intake. methods: a cross-sectional study was conducted on women hospitalized in the maternity during august-september . prepregnancy weight was self-reported. gestational weight gain and weight rate gain was determined by means of the weight registered in the maternity before delivery. nutrient intake during pregnancy was evaluated with a -item food frequency questionnaire. results: on average, protein provided . % ( %ci: . - . ), carbohydrate . % ( %ci: . - . ) and fat . % ( % ci: . - . ) of the total energy intake. there was a positive and consistent association between energy intake and maternal weight gain among the pregnant women (p = . ). the percent of energy from protein was associated with maternal weight gain rate (p = . ). women with a weight gain higher then media + sd had a higher intake of protein compared with those with medium (p = . ) and lower (p = . ) weight rate gain. no significant differences regarding fats and carbohydrates intake was noted. similarily, women with weight gain above the iom recommendations had a significant higher protein intake compared with those with a lower weight gain (p = . ). conclusion: a strong association was found only between protein intake and weight gain in the studied sample. a dietary pattern analyses would clarify the relation with weight gain during pregnancy. excessive weight gain and obesity before pregnancy was associated with large for geastational age newborns and prematurity. the aim of the study was to analyse the relation between maternal anthropometric indicators and apgar score. a cross-sectional study was conducted on women hospitalized in the maternity during august-september . multiple pregnancy and obstetrical pathology represented exclusion criteria. self-reported weight was used to estimate prepregnancy bmi. gestational weight gain was determined by means of the weight registered in the maternity before delivery. apgar score was determined by the neonatologist immediately after birth. results: in the sample studied, . % newborn had an apgar score lower than , thus indicating neonatal distress. there weren't noticed significant differences according to weight gain during pregnancy. among the mothers with newborns which had an apgar score lower than , . % had a weight gain lower, . % higher and . % within the iom′ s recommendations. however, excessive prepregnancy weight was associated with neonatal distress (p = . ): . % of women with prepregnacy bmi ! kg/m ; . % of the normal weight and % of the underweight gave birth children with low apgar score. conclusion: prepregnancy excesive weight was associated with neonatal distress, strenghtening the importance of achieving an ideal weight before conception. patients and methods used: six obese women (age . ae . years, bmi . ae . kg/m ) had fasting metabolic measurements taken via indirect calorimetry before and after weeks of a low starch diet. respiratory gases were collected for min using standard procedures in order to determine resting metabolic rate (rmr), respiratory exchange ratio (rer), and macronutrient oxidation (carbohydrate and fat). a paired sample t-test was used to evaluate significant mean differences from pre-to post-diet. results: after weeks on a low starch diet, subjects lost an average of . ae . kg despite the fact that this was not designed as a weight loss diet. rer decreased from . ae . to . ae . (p = . ) from pre-to post-diet measurements. further, carbohydrate oxidation decreased from . ae . to . ae . g/min (p = . ), and fat oxidation increased from . ae . to . ae . g/min (p = . ). changes in rmr were not significantly different. background: weight loss improves insulin resistance and hyperandrogenism in obese women with pcos but is unnecessary in lean women with pcos; however, meal timing and composition may influence glucose metabolism and hyperandrogenism. objective: to investigate the effects of two isocaloric diets with different meal timing on insulin resistance and hyperandrogenism in lean women with pcos. methods: sixty lean women with pcos were randomized to one of two kcal isocaloric diets with different meal timing: the number of young adults with ms is steadily increasing, but ms in children mainly incomplete according to the pediatricians' reports. so it was suggested that there are some flaws in the diagnostic criteria that lead to ms hypodiagnosis. hypothesis: using the clarified criteria may improve quality of ms detection in children. methods: in obese adolescents the ms components were analyzed by idf and clarified criteria. additionally abdominal obesity was analyzed by bmi sd and waist to height ratio; glucose intolerance by ogtt and homa-ir; dyslipidemia by fasting tg, ldl, hdl, tc (according to percentiles by ncep for children); blood pressure by the fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. results: the total number of detected ms components by idf vs. clarified ones: " " in . ae . % by idf; " " in . ae . % vs. . ae . % (p < . ); " " in . ae . % vs. . ae . % (p < . ); " " - . ae . % vs. . ae . % (p = . ); " " in . ae . % vs. . ae . % (p < . ); " " in . ae . % vs. . ae . % (p < . ). conclusion: using clarified criteria improves the quality of ms detection in children, which corresponds to a ms global concept of identifying high cardiovascular risk group. aim: polycystic ovary syndrome (pcos) is the most common endocrinopathy among women of reproductive age. pcos is connected with ovulatory disorders, oligomenorrhea, hyperandrogenism, infertility, and an increased miscarriage rate, and is frequently associated with insulin resistance (ir). multiple factors in the follicular fluid affect the fertilization and early embryonic development, including in women with pcos. the aim of this study is to evaluate the predictive value of follicular adiponectine regarding pregnancy outcomes in pcos vs. non pcos patients who underwent in vitro fertilization. material/methods: we designed a prospective study. group : (n: ) non pcos and group : (n: ) pcos patients according to roterdam criteria were included the study. basal ovarian reserve parameters, endometrial thickness, follicular luid adiponectine levels, clinical and laboratory ivf outcomes, pregnancy rates were studied. results: there were statistically significant differences in used gonadotropine dose, total oocyte number, mii oocyte number in non pcos vs. pcos groups (p: . ). but there were no statisticaly significant differences between the groups according to follicular fluid adiponectine levels (p > . ). we evaluated the correlation with adiponectine and ivf outcomes as endometrial thickness, mii oocytes number, fertilization rates and pregnancy rates, but there were no statisticaly significant correlation (p > . ). we could not find differences of follicular fluid adiponectine levels in the pcos vs. non pcos groups. although we could not find correlation with adiponectine and pregnancy rates, further investigations with larger numbers of cases are needed to clarify this subject. hypothesis: using the clarified criteria may improve quality of cardiovascular risk (cvr) evaluation in pediatric group. methods: comparative ms components detection in obese children by idf and clarified criteria as well as prognostic value relative to the myocardial remodeling and diurnal blood pressure patterns. results: it was established that the idf criteria (> ) are highly specific (sp = . ), but low sensitive (se = . ) with deterioration negative predictive value (npv = . ). clarified criteria (sum score > ) correspond to higher sensitivity (se = . ) without loss of specificity (sp = . ). conclusion: using the clarified criteria improves screening sensitivity and helps determine exact cvr. obesity is a global problem associated with numerous health issues includes type diabetes. bariatric surgery provides sustained weight loss and partial or complete diabetes resolution. micrornas (approximately nucleotides long) are post transcription regulators, which play important roles in conditions such as obesity and diabetes. the aim of this study is to investigate whether microrna profile is changed by bariatric surgery in postprandial state and if the altered microrna expression could contribute to long term post bariatric surgery benefits. both bariatric and sham-operated rats were given g of food min before sacrifice. total plasma and tissue rna from post-operative bariatric and sham operated rats were isolated and the microrna component was examined. principle component analysis clearly showed that bariatric surgery dramatically changed circulating microrna expression. correlation between microrna expression and metabonomics data indicated that certain plasma metabolites (for example, ketone bodies) are highly correlated. we also investigated liver microrna expression, microrna targeted mrna and metabonomics profile. mirna regulated key metabolic enzymes and receptors involved in the tca cycle, pentose phosphate pathway, gluconeogenesis and amp-activated protein kinase pathway. liver alanine, pyruvate and glucose levels were altered in bariatric compared to sham-operated rats. in summary, our data show that bariatric surgery changed both circulating and tissue microrna expression. we suggest that these alterations contribute to post bariatric surgery benefits by regulating key metabolic enzymes and receptors. the purpose of the study was to investigate serum concentrations of the asymmetric (adma) and symmetric dimethylarginine (sdma) and high sensitivity c-reactive protein (hs-crp) in hyperuricemic adolescents. patients and methods: the study group consisted of hyperuricemic patients aged median . years. the control group (c) contained healthy individuals with normal serum uric acid (sua) level. serum adma and sdma were measured by immunoenzymatic elisa commercial kits and were expressed in lmol/l. serum hs-crp was determined using nephelometric method (behring) and expressed in mg/l, sua was measured on the hitachi apparatus. results: hyperuricemic patients showed increased sdma (median: . q -q ( . - . ) lmol/l vs. controls . q -q ( . - . ) lmol/l, p < . ). serum adma values did not differ between two estimated groups (p > . ). the positive correlation was observed between adma and sua (r = . , p < . ) and sdma with sua and hs-crp concentrations (r = . , p < . ; r = . , p < . , respectively). we demonstrated that in adolescents with hyperuricemia increased serum sdma, but not adma levels were observed. no significant differences for adma and sdma between hypertensive and normotensive patients with hyperuricemia were found. the large, multicentre, prospective studies are needed to confirm if sdma might play a role in chronic inflammation in patients with hyperuricemia. objective and aim: supplementation of n- polyunsaturated fatty acids expresses anti-diabetic effect by enhancing insulin sensitivity and improving lipid metabolism. in this study we wanted to assess whether supplementation of n- can improve antioxidant status, preferably pon level, in the serum of type diabetic (t dm) patients. subjects and methods: twenty t dm patients ( females, eight males, age . ae . years, bmi . ae . kg/m ) were randomized to intake g marine oil ( . g epa and dha) during weeks, after weeks washout period. anthropometry, blood pressure measurements and fasting blood samples for metabolic parameters (glucose, hba c, insulin, cholesterol, hdl-cholesterol, triglycerides), hscrp, as well as oxidative stress enzymes [pon- , catalase (cat), superoxide dismutase (sod), glutathione peroxidase (gsh-px)] were obtained before and after treatment period. results: serum pon- activity response was increased by % from . to . (p < . ) as well as sod from . to . (p < . ) by epa and dha supplementation. it was associated with serum n- pufa increase by % (p < . ). there were no changes in anthropometry, glycemic control, insulin resistance index, the levels of total cholesterol, triglycerides and parameter of chronic inflammation (hscrp). only hdl-cholesterol increased after supplementation, from . to . mmol/l, with borderline significance (p = . ). conclusion: supplementation with . g n- pufa improves antioxidative status, pon activity and sod level, and repairs dyslipidemia in t dm patients. aim of this study: to determine the behavior of endogenous antioxidants markers and metabolic profile in non-proliferative diabetic retinopathy patients and methods: a cross-sectional study was designed with four groups: group : five healthy-volunteer subjects. group : patients with mild non-proliferative diabetic retinopathy (npdr). group : patients with moderate npdr. group : patients with severe npdr. serum endogenous antioxidants markers (determined by ua and b), glycemic profile (measured by fasting plasma glucose and hemoglobin a c), lipid profile (measured by total colesterol, triglycerides, high and low density lipoproteins-cholesterol), arterial pressure, renal profile (urea and creatinine analysis). serum-markers were quantified using enzymatic-colorimetric methods. results: patients with npdr had a significant increased serum lipid profile, glycemic profile and renal profile levels compared to the control group. ua and b levels showed increased trend in retinopathy groups compared with group . introduction: bone tissue has been recognized as an endocrine organ. recently it′s been found that levels of osteocalcin, a protein produced by osteoblast, is associated with glucose metabolism and lipids in human being. experimental studies showed associations between adiposity and levels of osteocalcin, however in the adolescent population is not quiet elucidated. objective: to establish the association between adiposity indexes and serum levels of osteocalcin in children and adolescents. materials and methods: in this study we included children and adolescents participants of the project "health worker cohort study" adiposity index were establish through bmi, waist circumference and dexa. the total concentration of osteocalcin was determined by chemiluminescence. through multiple lineal regression we evaluated the association between osteocalcin levels and the adiposity index. results: prevalence of overweight and obesity was . % abdominal obesity . %. it was observed a negative correlation between bmi, percentage of fat mass, waist circumference (p < . ). independently of the adiposity index included in the model, have obesity increases the risk of presenting low levels of osteocalcin (or: . ; % ci: . - . , p < . ) and adolescents with higher percentage of fat mass have five times more risk than adolescents with less fat mass of present low levels of osteocalcin (or: . ; % ic: . - . , p < . ). conclusions: adolescents with higher adiposity have more probability of have low levels of osteocalcin. objective: to evaluate the association between physical activity (pa) with presence of burnout syndrome (bs) and its three dimensions: emotional exhaustion, despersonalization and low personal accomplishment in health workers and educational sector. methods: a sample of imss workers, insp and uaem was obtained. after signing informed consent subjects answer a lifestyle questionnaire that included a pa questions and the burnout scale designed by maslach. anthropometric measurements were performed by previously standardized personnel (concordance coefficient of . - . ), with conventional stadiometer and calibrated scales previously tanita brand. we determined body mass index (bmi) based on the criteria of the center for disease control (cdc). pa was considered sufficient to perform or more minutes of daily pa. the data analysis was performed in the stata statistical package version . results: from the analysis of health workers and educational study participants′ cohort health workers. "female sex predominated by %. the mean age was ae years. seven out of ten participants performed < min of pa per day. a trend of higher prevalence of bs in those performing < min of pa per day was showed, to perform ! min of pa reduces the likelihood of developing bs in a % according to grunfeld criteria and % according to the ramı´rez's criteria. conclusions: to perform at least min a day is a protective factor to avoid the presence of bs, but only three out of ten participants to perform af. aims: with research showing that more than one third of this current generation of australian teenagers likely to become obese in adulthood, the need to arm our children with the skills to maintain a healthy weight has never been so urgent. the need for feed cooking program has been developed for teenagers to improve their ability to prepare and cook healthy food, and boost their knowledge about nutrition and support them to develop healthy habits for the future. methods: need for feed is delivered using school facilities and home economics teachers, but is delivered outside of school hours in an informal and engaging format. the program, which delivers h of tuition, focuses on improving participants' food preparation and cooking skills, budgeting and meal planning, basic nutrition knowledge, and attitudes and behaviours associated with healthy eating. results: evaluation demonstrates that participants improve in both skills and confidence in preparing and cooking healthy food, improve their knowledge of healthy eating guidelines and make tangible changes to their eating habits through increased consumption of fruit and vegetables, and reduced consumption of sugary soft drinks, cakes, chocolate and potato chips. conclusion: while the factors contributing to the obesity epidemic and growing rates of type diabetes are complex, the importance of arming the community with skills and confidence in cooking at home is being increasingly recognised. this program has shown that teenagers can develop the necccessary skills to support healthy eating through a targeted and engaging cooking education program. postprandial hyperglycemia is an early defect of type diabetes and the one of primary antidiabetic targets. the therapeutic approach for the treatment of postprandial hyperglycemia can be achieved by inhibiting a-amylase and a-glucosidase, key enzymes for starch digestion and further glucose absorption. in this study, the inhibitory activities of microalgal fucoxanthin against a-amylase and aglucosidase were determined as well as antidiabetic effect to induce differentiation in t -l preadipocytes using oil red-o staining. fucoxanthin exhibited weak inhibitory activity against rat-intestinal aglucosidase, while strong inhibitory activity against pancreatic aamylase in a concentration-dependent manner with ic values of . mmol/l and lmol/l, respectively. microalgal fucoxanthin significantly increased glucose uptake in t -l cell by . % at lmol/l. fucoxanthin inhibited lipid accumulation during adipocyte differentiation of t -l cell and no cytotoxicity was recorded for preadipocytes up to lmol/l. these results suggested that fucoxanthin may be useful approach for the prevention of type diabetes by inhibiting carbohydrate-hydrolyzing enzymes. university of vermont, burlington, vt, usa aims: we compared the effects of ad libitum low-fat, high-fiber and low-carbohydrate diets on caloric intake, anthropometry, and cardiometabolic risk markers in adults with the metabolic syndrome. methods: twenty-three women and men ( - years) with the metabolic syndrome completed a randomized crossover comparison of two -week diets. all meals (low-fat, high-fiber: - % carbohydrate, - % fat, - % protein, - g fiber/day; low-carb: - % carbohydrate, - % fat, - % protein, - g fiber/day) were prepared by a research dietician and consumed ad libitum. results: caloric intake was lower on low-carb ( ae vs. ae kcal/day; p = . ). only low-carb reduced body fat (À . ae . %; p = . ) and tended to produce greater weight loss (À . ae . kg vs. À . ae . kg; p = . ). both diets reduced fasting insulin (À . % to À . %; p < . ) and non-hdl cholesterol (À . % to À . %; p < . ). low-fat, high-fiber reduced serum cholesterol (À . %), while triglycerides (À . %) and vldl cholesterol (À . %) were reduced on low-carb (all p < . ). plasma ffa were elevated on low-carb (+ . %; p = . ). although flow-mediated dilation (fmd) was unchanged after low-fat, high-fiber ( . ae . % vs. . ae . %; p = . ), a trend for reduced fmd was observed after low-carb ( . ae . % vs. . ae . %; p = . ), producing a significant diet interaction (p = . ). introduction: better insulin schedules are needed to prevent hypoglycemic attacks. materials and methods: bs/time curve was plotted in a series of diabetic patients with and without treatment. the best fit curve was used by partial integration and mathematical extrapolation. the first and second derivatives of these curves were plotted by the use of special software and modified matlab. points of major mathematical and lifestyle interest were marked within the curve for correlation. daily variations were also registered. based on mathematical results, patients received auditory insulin and were compared with themselves and other patients under the same dose of insulin. results: although the bs/time curve and its first derivative are completely chaotic due to daily activity and unplanned meal intake the second derivative has some regularities and in regard to cutting the x axis every lambda minutes ( min ( min under % confidence interval. this shows that the innate glucose reducing potential of the body is exhausted after this time giving us the opportunity to treat with lower doses at these points. with this schedule patients needed less insulin and showed extremely better bs control. conclusion: preventing superimposition of innate bs reducing potency and external drugs can give rise to smoother bs control and less hypoglycemic attacks. besides, this can also be exploited in the management of prediabetic patients. introduction: type ii dm is generally regarded as a progressive disease with control of bs becoming more difficult with time. we wondered whether optimal therapy of the disease with "megatreatments" that can let the pancreas rest could reverse the disease. materials and methods: ten patients received optimal doses of insulin through the auditory channel for months. they were previously on oral hypoglycemic agents and relatively in good control. their bs were measured daily for months during the oral regimens before and after the auditory instillation. these two sets of measurements in addition to other subjective and objective parameters such as weight, sense of well being and hba c were compared. results: insertion of a strict insulin regimen in the form of auditory insulin instillation between two intervals of the same oral hypoglycemic agents (sandwich effect) causes a significant improvement in glycemic control and possibly needed dose. conclusion: as fairly good controlled patients were selected there is probably no doubt that more strict control of bs can reverse type ii diabetes progression. we have postulated that rest of the pancreas in the form of auditory insulin or strict diet can restore normal pancreatic response in a later occasion. based on a mathematical model of extrapolation we suggested that strict bs control for - years with a mean bs of mg/dl and possibly no attacks above mg/dl can reverse type ii diabetes in at least % of the patients. the diabetes epidemic could be controlled with effective prevention programs. these programs require accurate identification of subjects at risk. unfortunately, current prediction models have several deficiencies and are not being used. we present results comparing a novel model using association rule mining (arm) against three traditional models applied to data from the electronic medical record (emr). we used a cohort of , adults olmsted county, mn, residents without diagnosis of diabetes who visited mayo clinic between and . we collected pertinent baseline characteristics available as structured data in the emr. we assessed -year incidence of diabetes; a total of subjects developed diabetes during the follow up period. we used c-statistic (mean ae sd) to compare risk of diabetes estimated by framingham score, san antonio index, finrisk index and our arm model. results: some variables used by traditional risk models were not available as structured data in the emr. they were imputed as the mean of the variable as measured on the population in which the index was developed. with the exception of finrisk, all indices preformed similarly. the c-statistic for framingham score, san antonio index, finrisk index and arm model was . ae . , . ae . . , . ae . and . ae . , respectively. conclusions: our novel risk model using arm compares favorably to traditional models and has the advantage that it does not depend on a limited number of risk factors. this model is implementable at the point-of-care or population-based care where emr is in use, assuring universal utilization and improving implementation of preventive management. this study aimed to compare the effects of two types of interventions: diet vs. diet plus sea buckthorn pulp oil intake, in childhood obesity. the results were focused on fmd and imt values and risk factors for endothelial dysfunction. two groups of matched age, sex and bmi obese children (n = , - years old) and controls were enrolled. the measurements in the obese children were done before and after interventions: diet (low caloric, lipid, sugar intake for months) or diet plus sea buckthorn pulp oil intake ( mg/day for months). ultrasounds were used for fmd and imt measurements and colorimetric and elisa methods for biochemical parameters. obese children vs. lean ones had significantly increased values for imt, leptin, apob/apoa ratio, fasting c peptide, c reactive protein (crp), and reduced values for fmd and adiponectin. in the obese group treated only with diet, a light reduction in weight was observed, but no modification of atherosclerotic markers or metabolic improvement. in the obese group treated with diet and sea buckthorn pulp oil, fmd and adiponectin were unchanged, while imt was significantly reduced (p < . ), together with the other atheroscleroric risk factors: fasting c peptide (p < . ), leptin (p < . ). in conclusion, this study shows that sea buckthorn pulp oil intake has beneficial effects by preventing atherosclerosis in obese children. aims: as the rates of type diabetes continue to skyrocket across the globe, public health measures to reduce obesity appear to have limited success. while social marketing campaigns for obesity prevention have their place amongst a suite of strategies, their impact can be limited due to the gap between the campaign messages and individual's ability to identify opportunities for change in their own life. in queensland, a group of peak health agencies are working together to bridge that gap. methods: swap it, don′t stop it is an australian social marketing campaign promoting simple, everyday food and activity changes people can make to improve overall health. a multi channel health promotion and public relations strategy has been implemented to integrate the key messages of the swap it don't stop it campaign with grassroots healthy lifestyle opportunities to support individuals to make changes. this has been achieved by harnessing the collective actions of the non-government health sector to promote clear and consistent obesity prevention messages and by implementing a communications strategy that has connected community and stakeholders with tangible opportunities for healthy lifestyle changes at the local level. outcomes: through collaborative action amongst a broad network of service providers, the national campaign messages have been amplified through community events, radio, print and television stories that have highlighted examples of personal success and provided information that has inspired queenslanders to make small steps towards better health and reduce the risk of type diabetes and other chronic diseases. background and aims: proposed changes to gdm diagnostic criteria are anticipated to increase diagnosis rates leading to rising demand for support during pregnancy. lack of awareness of risks associated with gdm acts as a barrier to healthy lifestyle adaptation and postpregnancy screening ( , ) . the you program delivers a range of strategies to support women at diagnosis, facilitate behaviour modification ( ) and re-enforce importance of post pregnancy screening. methods: newly diagnosed women and their support networks are educated about gdm, risk reducing behaviours and the health care system through a purpose built website and a suite of print resources. specific resources were developed for at risk groups including indigenous australians and women from non-english speaking backgrounds. women are encouraged to join a national register to receive post pregnancy screening reminder letters and text messages in conjunction with regular newsletters containing family-friendly information on healthy lifestyle behaviours and screening. nominated gp's are also sent screening reminders to prompt women to attend screening. results: engagement with the website and newsletters is high, screening reminders evaluated positively with focus groups and participants indicated that they intended to attend their post natal screening. conclusion: you delivers a multi-strategy approach that engages and supports women at diagnosis and re-enforces the importance of screening and behaviour modification during and post pregnancy. family members and peers were recognised as important sources of support and educated to encourage screening and behavioural changes. these low-cost interventions can help reduce prevalence or morbidity in women affected by gdm associated type diabetes. however smoking cessation has many benefits for smokers, but the most important challenge for smoking cessation is withdrawal symptoms during the first days and months of cessation which can be an important reason for unsuccessful in the smoking cessation process. however, many methods are available to help quit smoking, but acupuncture is used for the treatment of nicotine dependency with the aim of reducing of withdrawal symptoms experience. therefore, the aim of this study is to determine the role of acupuncture in success at quit smoking in the iranian samples. methods: one hundred and thirty-two men smokers who were ready to quit smoking were participated in the study. the participants were divided to two groups by randomized sample method. one group was for acupuncture and another group was for acupuncture in shame points. the mean age of smokers was ae years. all participants followed for year and the quit rate evaluated in , , months of the study. the results show, while . % in case-control and . % in control group could quit smoking in the first month of study; but in the month of the study . % in case-control and . % in control group were at quit rate. the quit rate short and long term in case group was higher than control group. therefore, physicians should play an active rate in control of smoking by ensuring and counseling and use of various pharmacology and non pharmacology methods for increase quit rate. panjab university, pgimer, chandigarh, india introduction: , -dimethylhydrazine (dmh)-induced colon carcinogenesis in rats is a reliable model to explore molecular mechanism involved in progression of colorectal cancer from adenoma to carcinoma sequence. objective: to study the transcriptional and translational levels of various genes involved in tumorigenesis pathway of dmh induced rat model. methods: two groups of chow-diet-fed, male sprague-dawley rats, aged weeks (n = /group) were fed a normal diet and injected subcutaneously for two time durations of and weeks dmh at a dose of mg/kg body weight/week or with ethylene diamine tetraacetic acid (edta)-saline. macroscopic and microscopic analyses were performed for confirmation of adenoma and carcinoma. mrna expression of nfkb and caspase- genes were determined by real-time pcr. immunohistochemistry was also performed for expression of above genes. results: gross examination of weeks dmh treated colon showed polypoid lesions and multiple tumors were formed after weeks dmh treatment. histopathological studies confirmed the colon carcinogenesis from adenoma-carcinoma sequence by type of tumor, degree of differentiation and invasion of tumors. in adenomatous and carcinomatous colonic tissues, mrna expression of nfkb was increased by . and . fold respectively, whereas expression of caspase- was reduced by . and . fold respectively. immunohistochemistry studies showed the increase expression of nfkb and reduced expression of caspase- in colonic tissues of dmh induced rat model as compared to controls. the observed data strongly implicates that dmh induced colon carcinogenesis altered the apoptotic machinery by modulating the expression of various genes involved in this pathway. objective: identify anthropometric indicators that present the greatest correlation in the diagnosis of some metabolic syndrome components in adolescents and its association with gender, age, and family history. methods: cross-sectional study with adolescents between and years of age of a public high school in the mexico city. bmi was used to diagnose overweight and obesity according to cut-offs proposed by the international obesity task force. waist circumference (wc) and waist-to-height ratio (whr) were used as fat distribution indexes. results: . % of the students were male. the prevalence of overweight and obesity were . % and . %. there were association between overweight-obesity and the average values of wc, whr, and blood pressure (p < . ). the correlation between waist circumference and bmi and waist-height were the strongest (r = . and r = . , respectively). we recommend using wc and whr in clinical practice as simplified indicators to predict risk of metabolic syndrome in mexican adolescents. c. saely, a. muendlein, a. vonbank, k. geiger, p. rein, h. drexel background: the novel adipocytokine chemerin has been suggested to be linked to insulin resistance and to the metabolic syndrome (mets). its association with coronary artery disease (cad) is unclear. we hypothesized that chemerin is associated with both angiographically determined cad and with the mets. we measured serum chemerin in patients undergoing coronary angiography for the evaluation of established or suspected stable cad; the mets was defined according to ncep-atpiii criteria; significant cad was diagnosed when coronary stenoses ! % were present. results: chemerin was higher in mets patients (n = ) than in subjects without the mets ( ae vs. ae ng/ml; p < . ). it did not differ significantly between patients with significant cad (n = ) and those without significant cad (p = . ). when both, mets and cad status were considered, chemerin was higher in mets patients both among those who had significant cad ( ae vs. ae ng/ml; p = . ) and among those who did not have significant cad ( ae vs. ae ng/ml; p < . ); it did not differ significantly between patients with significant cad and subjects without significant cad among mets patients (p = . ) nor among subjects without mets (p = . ). analysis of covariance (ancova) showed that a large waist circumference as well as elevated trigylcerides were independent predictors of elevated serum chemerin (f = . ; p < . and f = . ; p = . ). we conclude that chemerin is significantly associated mets but not with angiographically determined cad. the overall association of chemerin with the mets is carried by its association with visceral obesity and elevated triglycerides. objective: resistin is a novel adipocyte-secreted hormone proposed to link obesity with diabetes. the role of resistin gene polymorphism in insulin resistance and metabolic syndrome is controversial till date. the present study was attempts to investigate the relationship between resistin gene polymorphism with circulating resistin level, metabolic risk factor and insulin resistance in north indian population. methods: this is a case-control study; total healthy subjects were selected for the study. out of which (age . ae . years) were with metabolic risk factor and age matched control (age . ae . years) were without metabolic risk factors. we estimated homeostatic model assessment (homa) index, circulatory resistin, and lipid profiles. the genotyping of resistin-c g were carried out using pcr-rflp method digested with bbsi restriction enzyme. results: homozygous mutant genotype (cc) (cc v/s cg + gg) (p = . : or = . : % ci = . - . ) and mutant allele (g) (p = . : or = . : % ci = . - . ) of the c/g polymorphism was significantly less frequently observed in the control population as compared to study group. furthermore, on dividing the subjects into two groups according to the absence (resistin - ) or presence (resistin- ) of the mutant g allele, significantly high levels of resistin (p = . , or = . , %ci = . - . ) and insulin resistance (p = . , or = . , %ci = . - . ) were observed in resistin- group as compared to resistin- group. conclusion: our results suggest that the c/g mutation of the resistin gene is likely to play an important role in the development of metabolic syndrome and metabolic abnormalities. king george's medical university, lucknow, rims, saifai, etawah, india objective: adiponectin has been shown to be an insulin-sensitizing hormone and negatively associated with components of metabolic syndrome. present study was attempted to investigate the adiponectin polymorphism in metabolic syndrome and insulin resistance. methods: the adiponectin t g and g t polymorphism has been studied in females with metabolic syndrome and control without metabolic syndrome according to ncep atp iii criteria, . circulating adiponectin and leptin levels were determined by sandwich elisa method and insulin resistance by the homeostasis model assessment (homa) index. the polymorphism of adiponectin t/g and g/t gene were determined by pcr-rflp method. results: significant difference were found for circulating leptin level except adiponectin level ( . ae . vs. . ae . ), and in metabolic risk factors among metabolic syndrome and without metabolic syndrome females. homozygous mutant genotype (gg) (tt vs. tg + gg) (p = . : or = . : % ci = . - . ) and mutant allele (g) (p = . : or = . : % ci = . - . ) of the -t g gene and mutant allele (t) (p = . : or = . : % ci = . - . ) of the g t polymorphism were significantly less frequently observed in the control population as compared to study group. the results of the present study concluded that the mutation of the adiponectin t/g and g/t gene might play a important role in obesity associated metabolic syndrome and metabolic abnormalities except insulin resistance, glucose level and insulin levels in the north indian women due to mutation of the adiponectin gene is associated with decreased adiposity which is protective one for metabolic syndrome design: cross-sectional study of patients with good (excess body mass index lost (ebl) > %) and poor weight loss (ebl %) > months after rygb. material and methods: sixteen patients with good weight loss and patients with poor weight loss were included in the study. the patients underwent dual energy x-ray absorptiometry scan, indirect calorimetry and a -h multiple-meal test with measurements of glucose, insulin, total bile acids (tba), glucagon-like peptide (glp)- , peptide yy - (pyy), cholecystokinin (cck), ghrelin, neurotensin, and pancreatic polypeptide (pp) as well as assessment of early dumping and appetite. results: suppression of hunger was more pronounced in the good than the poor weight loss group in response to the multiple-meal test (p = . ). in addition, the good weight loss group had a larger release of glp- (p = . ) and a greater suppression of ghrelin (p = . ) during the test, whereas the postprandial secretion of cck was highest in the poor weight loss group (p = . ). pyy, neurotensin, pp and tba release did not differ. early dumping was also comparable. differences in resting energy expenditure between the groups were entirely explained by differences in body composition. conclusion: favorable meal-induced changes in hunger and gut hormone release in patients with good compared to poor weight loss support the role of gut hormones in the weight loss after rygb. background: the objective of this study is to explore changes in the vascular tone over the endothelial, neurogenic and myogenic frequency ranges during a contralateral cold pressor test by performing the wavelet analysis of skin temperature fluctuations and to compare the results obtained in healthy subjects and in patients with metabolic syndrome (ms) and type diabetes. methods: thirteen adults with type diabetes aged - years (average diabetes duration of . ae . years) and adults with ms aged - years participated in this pilot study. the control group included practically healthy men and women aged - . the lowfrequency fluctuations of skin temperature in the appropriate frequency ranges, registered during contralateral cold test, were used as a characteristic reflecting the mechanisms of vascular tone regulation. results: the response to cold pressor test in patients with type diabetes and with ms differs essentially from that of healthy subjects. patients with ms show changes in the amplitude of skin temperature fluctuations similar for patients with type diabetes in the endothelial range. the endothelial dysfunction occurs in the pre-clinical stage of diabetes and manifests, in particular, as a disturbance of the endothelial part of vascular tone regulation. with progression of the glucose metabolic disorders the pathological process is worsened due to violation of the neurogenic vasodilatation mechanisms. fetal metabolic programming states that early life nutrition is implicated with the risk of later disease development and both underand overnutrition during gestation might predispose individuals to develop obesity or diabetes later in life. obesity operations called "gastric bypass" operations have shown unexpected involvement of the small intestine in diabetes pathophysiology as it in most cases result in a complete resolution of the diabetes before weight loss. therefore we hypothesize that the small intestine is a subject of metabolic programming and that this programming can predispose for diabetes development. twin-pregnant ewes where fed a normal, a low or a high diet during the last weeks of gestation and the twin lambs where fed either a conventional or a high fat, high carbohydrate (hchf) diet during the first months of life. feeding challenge tests were performed on all lambs and some were slaughtered with collection of intestinal tissue for qpcr. the hchf diet increased the blood level of glucose, insulin and tg and increased the intestinal expression of a range of genes involved in growth, vascularization as well as digestion and absorption. the maternal low and high diet had effects on gene-expression, however the results vary between genes. these observations suggest that small intestine function has been programmed by the late-gestation low or high diet at gene expression level, whereas the physiological metabolic functions has mainly been affected by the hchf diet at such a young age. further investigations on the long-term effects of early nutrition are required. background: liposuction is considered as the treatment for the metabolic complications of obesity. the aim of this study was to evaluate the effect of abdominal liposuction on leptin and interleukin- (il- ) expression in adipose tissue and serum concentration. material and methods: the study included consecutive patients ( females, seven males) aged ae years with bmi ae kg/m , non-diabetic, apparently healthy, who underwent liposuction in mandala beauty clinic in pozna n, poland. the patients were examined clinically and the blood was withdrawn for routine laboratory tests (hematology, glucose, lipids, coagulation). leptin (r&d) and high sensitivity il- (hsil- ) (abcam) were analyzed in the supernatant of adipose tissue homogenate and in serum, by means of elisa. results: the expression of leptin in adipose tissue positively correlated with white blood cells count before liposuction (rs = . , p = . ). it was also higher (p = . ) in patients with bmi ! . ( . ; . - . ng/mg protein; median, interquartile range) than in subjects with bmi < . ( . ; . - . ng/mg protein). following liposuction, after month, serum leptin levels were lowered in smokers ( . ; . - . ng/ml), when comparing with baseline ( . ; . - . ng/ml). serum level of the adipokine, both before (rs = . , p = . ), and after (tau kendall = . , p = . ) liposuction correlated with tissue expression of leptin. no differences in adipose tissue expressions and serum levels of hsil- were observed month after liposuction. conclusion: a count of circulating leukocytes, even presented within references, affects the increasing adipose tissue expression of leptin. smoking status favorably affected the influence of liposuction on serum leptin levels. liposuction has no short-term effect on serum il- concentrations. r.a.l. sertié , s.a. sertié , a.r.g. proenc ßa, t. lima-salgado, a.c. oliveira, f.b. lima introduction: all adaptations acquired through physical training are reversible during inactivity. significant reductions in maximal oxygen uptake (vo max ) are observed within two-four weeks of detraining. conversely, the consequences of detraining on adipose tissue are poorly known. aim: to investigate the physical detraining effects on metabolism and cellularity of rat periepididymal adipose tissue. methods and results: male wistar rats, ageing weeks, were divided in three groups: trained (t) for weeks; detrained (d), (trained for weeks and detrained for weeks), and age-matched sedentary (s). training consisted in treadmill running sessions ( h/day, day/week, - % of the maximal capacity). the morphometric analysis of pe tissue disclosed significant differences between the groups. the adipocyte sectional area of group d was significantly bigger than t and s ( ae . lm vs. . ae . lm vs. . ae . lm , respectively). compared to t the cells of d animals showed % increased ability to perform: lipogenesis, either spontaneously or insulin stimulated and isoproterenol-stimulated lipolysis. basal lipolysis did not change. a % reduction in apoptosis was observed in groups t and d in relation to s. some gene expressions were changed in d vs. s: adiponectin (three-fold up) and ppar-gamma (two-fold up). pref- gene was three-fold higher in t vs. s. conclusions: these results suggest that adipogenesis was stimulated in this group. detraining causes significant increase in adipocyte size and lipogenic capacity. as pe fat cell apoptosis was reduced in d and t. background: chronic red wine (rw) consumption has been associated with a decreased cardiovascular disease risk, mainly attributed to an improvement in lipid profile. rw intake is also able to change gut microbiota composition. high-fat intake has recently been reported to increase metabolic endotoxemia. the gut microbiota has been proposed as the main resource of plasma lipopolysaccharides (lps) in metabolic endotoxemia. objective: to analyze the effect on lps concentrations of chronic rw consumption and acute rw intake in relation to high-fat intake in middle-aged men. design: for the chronic study middle-aged male volunteers were randomized in a crossover trial and after a washout period all received rw, dealcoholized red wine (drw), or gin for days. the serum lps concentration and changes in fecal microbiota were quantified before and after the treatments. for the acute study, five adult men underwent a fat overload or a fat overload together with rw, drw or gin. baseline and postprandial serum lps concentrations and postprandial chylomicron lps concentrations were measured. results: chronic rw consumption led to a significant decrease in lps concentrations compared to baseline. in addition, lps concentrations correlated negatively with bifidobacterium and prevotella levels. there were no differences in postprandial serum or chylomicron lps concentrations between acute rw, drw or gin intake together with a fatty meal. postprandial chylomicron lps concentrations correlated positively with the increase in triglyceride concentrations. conclusions: chronic rw consumption decreases lps concentrations, but it is not able to attenuate the postprandial lps increase induced by a fat overload. physical inactivity increases the risk of metabolic disease, associated with perturbations of muscle energy metabolism. the aim of this study was to assess the effect of exercise training on adiposity, physical fitness and muscle energy metabolism in obese individuals with attributes of ms. methods: sedentary individuals (m/f / ; age . ae . years, bmi . ae . kg/m ) completed -months endurance or strength (n = / ) training program ( h, -times/week). subcutaneous and visceral adiposity was measured by mri. phosphorus mr spectroscopy ( p-mrs) was used to assess the energetic status of muscle in vivo by measuring phosphocreatine (pcr), atp, inorganic phosphate (pi) and maximal oxidative flux (q max ), after exercise-or magnetic-induced equilibrium perturbation (n = ). the samples of skeletal muscle were taken by needle biopsy (vastus lateralis). cytochrome c oxidase (cox) activity of permeabilized muscle fibers was measured by oxymetry and maximal aerobic capacity (vo max) by bicycle ergometry. free-living ambulatory activity was monitored by accelerometers. results: subcutaneous adiposity did not change with training. however, strength training decreased visceral adiposity (p < . ). training increased physical fitness (vo max, n = , p = . ) and in vivo muscle energy metabolism ( p-mrs: q max , pcr, atp, n = , p < . ), without a significant effect on cox activity (n = . ). depletion of muscle pcr was negatively associated with cox activity (p = . ). vo max was not associated with muscle metabolism (p > . ). free-living activity increased during training (p < . ). conclusions: three months training of obese individuals was sufficient to increase both cardiorespiratory fitness and muscle metabolism, assessed by p-mrs. strength training was more efficient in decreasing visceral adiposity. background: the amelioration of metabolic complications of excessive body mass by liposuction is intensively discussed, as the metabolic surgery is proposed for future diabetes therapy. we have undertaken the study on the short-term effect of liposuction on insulin resistance parameters. material and methods: we included in the study consecutive patients ( females, seven males) aged ae years with bmi ae kg/m , who underwent liposuction in mandala beauty clinic in pozna n, poland. the non-diabetic, apparently healthy patients were examined clinically, blood was withdrawn for baseline routine laboratory tests (hematology, glucose, lipids, coagulation). insulin levels in serum and its content in adipose tissue were evaluated by means of elisa (diasource, sunrise tekan). insulin resistance/ sensitivity indexes: homa-ir, quicki and mcauley were calculated. one month observation included re-evaluation of glucose, lipids and insulin along with the indexes. data are presented as mean ae sd or median; interquartile range. we have observed the decrease in glucose concentrations ( ae vs. ae mg/dl, p = . ) and insulin levels ( ; - vs. ; - mu/l, p = . ) month after liposuction, comparing to baseline. homa-ir ( . ae . vs. . ae . , p = . ) and mcauley index ( . ae . vs. . ae . , p = . ) were improved month after liposuction, however no effect on quicki has been found. triglycerides concentrations month after liposuction were lowered comparing to baseline ( ; - mg/dl vs. ; - mg/dl; p = . ). in multiple regression analysis age was independent factor that affected insulin content in adipose tissue in males (b = . , p = . ). conclusion: liposuction causes beneficial effect on insulin resistance parameters in short-term observation of non-diabetic patients. background: a large number of studies showed that community-based health promotion is an effective way of preventing and treating chronic diseases. however, participation rate is very low for health education programs in community health centers (chcs); that of the program is not attractive, in part, because it is not individualized. using diabetes risk assessment tool based on electronic health records (ehr) data for diabetes risk prediction could help to early identify high-risk groups and reduce the incidence of diabetes through health education and lifestyle changes to control risk factors. objectives: to conduct community research to understand the situation of community diabetes prevention and control; to initially established prediction model of diabetes risk factors based on ehr data in chcs. the project randomly selects four districts in shanghai, using a combination of quantitative research and qualitative research method. get ehr data from each chc, attempts to establish the predicted model for diabetes, and test the sensitivity and specificity of the model. outcome measures: the prediction model include age, gender, blood pressure, smoking, drinking, body mass index, family history of diabetes based on ehr data. as pr(d) ! . , the sensitivity is . %, specificity is . % and area under roc curve (auc) is . . the empirical results will contribute to a better understanding of how the diabetes management in chc is important and provider the targeted self-management materials to improve health outcomes as well as evidences directly applicable in improving china's health policy reforms. a. schmid, a. kopp, m. bala, s. leszczak, i. ober, m. mü ller, a. schä ffler internal medicine i, university hospital regensburg, regensburg, germany introduction: the adipokine chemerin has an important role in insulin sensitivity and insulin secretion. elevated systemic chemerin concentrations correlate with obesity and insulin resistance. this study investigated chemerin serum levels of healthy volunteers undergoing an oral fat tolerance test (oftt) and their correlations with gender and markers of insulin sensitivity and inflammation. we further tested effects of the sex hormones estradiol and testosterone on chemerin secretion from adipocytes in vitro. methods: hundred overnight fasted healthy volunteers participating in the study underwent an oftt. after oral uptake of lipid suspension, venous blood was drawn at , , and h. subjects were characterized by anthropometric and standard laboratory parameters. chemerin levels were measured by elisa. mature murine t -l adipocytes were stimulated with estradiol and testosterone. concentrations of secreted chemerin were measured by elisa. results: while there were no significant changes in individual chemerin concentrations resulting from the lipid load, mean chemerin levels in sera of female probands were found to be significantly higher when compared to males ( . ae . vs. . ae . ng/ml, p = . ). the correlation of chemerin with insulin and c-peptide concentrations also was gender-specific. along with these findings, chemerin secretion from mature t -l adipocytes was shown to be affected by estradiol and testosterone treatment. conclusion: human chemerin concentrations are higher in females and there is a gender specific regulation upon stimulation with sex steroids. chemerin is not responsive to an oral lipid load. objective: to study the predictors of change in bmi with respect to time among physically active subjects. methodology: the present study was conducted among physically active individuals in delhi. data was collected longitudinally with a monthly follow up of months. various anthropometric and physiological measurements were taken using standard protocol. the analysis has been performed with mixed effect modeling to assess subject's variation for parameters with respect to time. r . . software with nlme package was used. an akaike information criterion (aic) was applied to find the consistency and measure the relative goodness of fit of a statistical model. : bmi as an important factor was taken as dependent variable and using aic, gender, blood pressure and weight were independent variables or fixed and random variables for months of longitudinal study. using generalized linear model (glm), bmi was dependent variable and other parameters i.e. gender, systolic blood pressure (sbp), diastolic blood pressure (dbp) and weight were independent variables. the regression coefficient obtained for gender with respect to bmi (as response variable) was À . . the estimated values for sbp, dbp and weight were À . , . and . respectively. the reduction of bmi among females was more in comparison to males. the reduction rate of sbp, dbp and weight with bmi was very low with respect to time. a.e. andreazzi , s. grassiolli , j.c. de oliveira , r. torrezan , s.t. paes , m.s. silva , r.m.g. garcia , p.c.d.f. mathias department of physiology, federal university of juiz de fora, juiz de fora, biology, state university of maring a, maring a, biology, federal university of juiz de fora, juiz de fora, brazil obesity is a worldwide epidemic and the most important factor in metabolic syndrome onset. the involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium l-glutamate (msg). to access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. catecholamine content and secretion from isolated adrenal medulla were measured using the trihydroxyindole fluorescence method. high-performance liquid chromatography (hplc) was used to measure plasmatic adrenaline. intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. msg treatment increased the epididymal and retroperitoneal fat pad mass by . % and . %, respectively, compared with control animals (p < . ). the nerve firing rate of obese rats was decreased . % compared to the rate for lean rats (p < . ). pre-diabetic rats showed a % reduction in basal catecholamine secretion from the adrenal medulla and % lower plasma adrenaline concentration compared with the control animals (p < . ); whereas catecholamine secretion induced by carbachol, elevated extracellular potassium and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. both glucose intolerance and hyperinsulinaemia were observed in obese rats. adrenaline strongly inhibited glucose-induced insulin secretion in obese animals ( %, p < . ). these findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in pre-diabetic obese rats. objective: the aim of the present study was to evaluate the influence of physical activity patterns on cardiovascular health. the study was conducted in delhi, among adult punjabi males and females. total sample of subjects was taken for the study. data was collected crosssectionally using multistage stratified sampling. according to pattern of physical activity using self administered proforma, two groups were formed, one regular physical activity group (rpa; at least days/week brisk walk for min, doing yoga for min), and the other irregular physical activity group (ipa; < days a week with no consistency). various anthropometric and physiological measurements were taken using standard protocol. results: higher percentage of subjects with irregular pattern of pa was at risk of developing high bp, obesity and triglycerides. higher values of whr, whtr among them showed that group was more disposed to cardiovascular health problem. males with ipapattern had . times, . times and . times more risk of increasing regional adiposity using whtr, whr and wc respectively. among females, whtr, whr and wc respectively showed . times, . times and . times higher risk of developing regional adiposity with irregular pattern of pa. the increased risk of being obese was . times more among males with irregular pattern of physical activity while among females fat percentage and obesity level using bmi category were found to be at a risk of . times and . times respectively. conclusion: subjects with regular pattern of pa showed higher percentage of normal values of various cardiovascular and obesity markers. irregular pattern of pa increased the risk of regional and general adiposity markers besides that of high bp. materials and methods: serum glycemia, insulin and c-peptide level were measured at ogl hours - st- nd in: seven healthy controls, patients with ms and with cushing; mean age was . - . - . , bmi - - , ogl glycemia: . - . - . ; . - . - . ; . - . - . respectively. all patients had bp > / mmhg and triglyceride level > . mmol/l. homa assessment: (fasting insulin, pmol/l fasting glucose, mmol/l): . . c-peptide and insulin increase above fasting level (in pmol) per g of ingested glucose was calculated. results: (*p < . vs. control). homa was . - . *- . * and fasting c-peptide and insulin level were / , / *, / * pmol/l in control, ms and cushing respectively. to the st hour of ogl the corresponding data were: / , / * and / * and increase of c-peptide and insulin concentration per g of ingested glucose was almost equal: / . - / . - / . pmol/l. the degree of c-peptide increase to the st hour was twice less than in control and increased fasting hepatic insulin clearance lowered almost to control level (judging by c-peptide/insulin ratio). to the nd hour of ogl c-peptide and insulin level became similar to fasting data. conclusion: ir characteristics were similar in ms and cushing disease. insulin requirement increase on the top of ogl was equal to control. judging by c-peptide/insulin changes ir stops manifesting on the top of glycemia during ogl (probably due to normalizing hepatic insulin clearance). introduction: ir is atfr of high potential, but also one of the first signs of a ateroscl. process. condition when the body has too much insulin at in the same time too much glucose is the resistance of peripheral tissues to the action of insulin. objectives: to investigate the relationship of concentrations of insulin and glucose in the peripheral blood, but also the conc. of gh, becose normalisation of gh secretion could corrects hiperinsulinemia and insulin resistance. on the other hand reduced gh secretion often points to the high expression of somatostatin and the presence of stress, which leads to secretion of somatostatin. further increase in visceral adipose tissue and ffa relise under stress can worsen the condition of and insulin resistance. aims of study: conducted therapeutic program (combination of dietary and physical activity), in which only the group edu implemented and behavioral therapy. monitoring parameters of glycemic control: fasting glucose, fasting insulin and gh and insulin sensitivity of peripheral tissues to insulin, always from in one blood sample, parallely in two different phases of therapy. we used anova-manova statistics to determine the significance of an differencies. material and methods: determining of glucose, insulin, and growth hormone. as and qucki index for determining od insulin sensitivy conclusion: ours finding indicate that the synergistic effects of dieting and increased physical activity improves glucoregulation, reduce excessive insulin secretion and restoration of gh secretion. but only behavioral therapy may lead to permanent changes in nutritional habits and lifestyle. the metabolic and endocrine dysfunctions that may occur with polycystic ovary syndrome (pcos) can be associated with future comorbidities such as diabetes, cardiovascular disease, and endometrial cancer. although a definitive link between pcos and these chronic illnesses has not been demonstrated, there is significant overlap in the clinical characteristics of these disorders. consequently, the issue of identifying and measuring potential conditions that may be associated with pcos is a priority and should be the standard of practice in its management. hiperhomocysteinemia has been shown as independent predictor of cardiovascular events in patients with atherosclerosis. the aim of our study was to determinate levels of homocysteine in woman with polycystic ovary syndrome compared with healthy woman. thirty patients (age, , ae . ) with pcos and (age, . ae . ) healthy woman were involved in the study. blood samples were collected in early follicular phase. total homocysteine was measured using fluorescent immunoassay. statistically significant differences in serum concentration of homocysteine were observed between groups. mean homocysteine level we found as ( . ae . vs. . ae . ) in pcos and normal group respectively (p < . ). for macedonian population we found statistically significant increased homocysteine levels in woman with pcos. although the mean homocysteine levels are within normal limits, there are significant higher mean homocysteine concentrations between these two groups. because an increased concentration of thcy has been shown as and independent risk factor for cardiovascular alterations, it is essential in this group of woman to be taken measures for early prevention. a. alkandari, n.j. gooderham, h. ashrafian surgery and cancer, imperial college london, london, uk globally million people are obese and prevalence is increasing. obesity and its many co-morbidities are leading causes of mortality and morbidity and pose substantial socioeconomic burdens on health services. bariatric surgery is a form of gastrointestinal surgery that leads to sustained weight loss, a decrease in cancer risk and resolution of type diabetes. micrornas are a family of small, endogenous, non-coding rnas that regulate gene expression at the posttranscriptional level. micrornas control expression of over half the human transcriptome and are involved in processes fundamental to both normal physiology and disease, including obesity, diabetes and cancer. we hypothesise that urinary micrornas are biomarkers for bariatric surgery reduction of type diabetes. here, we looked at expression of micrornas involved in diabetes in urine samples prior to bariatric surgery and at months and year postoperatively. urinary rna was obtained using the mirvana paris kit and microrna expression was determined through quantitative pcr. we found significant increases of two to three fold postoperatively in the expression of three micrornas involved in diabetic nephropathy. these findings are consistent among patients undergoing laparoscopic roux-en-y gastric bypass and sleeve gastrectomy. our results indicate that bariatric operations can modulate post-translational effects in end-organs postoperatively and may contribute to the beneficial effects noted after these procedures. hepatic insulin resistance and the ensuing impairment of hepatic glucose metabolism is a major contributor to hyperglycemia in metabolic syndrome. various factors appear to act in parallel to elicit hepatic insulin resistance. while impaired fatty acid handling with a resulting activation of pkc isoforms is one established route, a subacute inflammation also appears to contribute and the impact of cytokines on the insulin signaling cascade is well established. by contrast, the role of small lipid mediators e.g. prostaglandins and sphingolipids, which are also affluent in inflamed tissue, is not well characterized. the current study addressed this question. in a wide array of genetic and diet-induced mouse models of the metabolic syndrome, hepatic expression of key enzymes of prostaglandin formation was induced. prostalgandin e , which is released predominantly from kupffer cells, directly attenuated insulindependent hepatic glucose utilization by an erk / -dependent serinephosphorylation of irs and hence attenuation of insulin-dependent akt-phosphorylation. in addition, pge enhanced lipid accumulation in hepatocytes by inhibiting mitochondrial fatty acid oxidation and vldl formation. furthermore, pge in an autokrine feed forward loop increased the formation of oncostatin m in kupffer cells, which in turn inhibited insulin signaling in hepatocytes by inducing socs . similar to pge , sphingosine- -phosphate, whose production was strongly enhanced by exposing hepatocytes to palmitate, attenuated insulin-stimulated glucose use and the induction of glycolytic enzymes in hepatocytes. in summary, the study provides first evidence that in addition to the established mechanism, small lipid mediators like prostaglandins and sphingolipids may impact on hepatic insulin resistance. background: the progression of childhood cardio-metabolic risk factor to adulthood suggests early origin of pathogenic pathways leading to chronic non-communicable disease as diabetes. objective: we sought to examine the distribution of insulin resistance (homa-ir) among children inhabiting delhi and clustering of cardio-metabolic risk variables among them. research design and methods: a cross sectional study was conducted among children aged - years. estimates of insulin resistance were derived on the basis of homeostatic model assessment. the th percentile of homa-ir for normal weight subjects with normal fasting glucose was considered as cutoff for insulin resistance. total body fat was assayed using body composition analyser (tbf- h a) employing bioelectric impedance technique. bmi was converted to age-and sex-standardized percentiles and subjects were classified as underweight if bmi < th and overweight if bmi was > th percentile. children with blood pressure > th percentile, adjusted for age and sex were categorised as hypertensive. information on socio-demographic features and family history of diabetes was obtained through standardized questionnaire. result: independent student t-tests showed significantly higher percentage of body fat among girls ( . %) as compared to boys ( . %). mann-whitney u-test analysis depicts significantly higher level of fasting sugar among girls ( . mmol/ml) than boys ( . mmol/ml). out of children ( . %) were insulin resistant. among them five were underweight while seven were overweight, / (sbp/dbp) were hypertensive and had family history of diabetes. conclusion: high prevalence of insulin resistance, a precursor of diabetes among these children foreshadows a worrisome trend for the burden of type diabetes in near future. both aims, losing weight as well as improving metabolic conditions, should be reached within the first weeks of an intervention program already. therefore, results of a short-time intervention concept should be presented. in answer to a regional tv-report dealing with "successful weight loss", overweight adults contacted the freiburg institute of preventive medicine (ipm) to participate in a -week intervention program. after looking for exclusion criteria, patients ( . ae . years, . ae . m/kg bmi) could be included. the ipm concept consists of an initial consultation in energy balance and life style changes, the use of a soy-yoghurt-honey product (almased â , per day as meal replacement), and the facility for guidance by phone. forty patients completed the program attending the exit examination. starting from a comparable bmi, the females were younger (n = ; . ae . years) than the males (n = ; . ae . years) and showed less associated risk factors. of significantly older age was the subgroup of patients with metabolic syndrome (ms) or type diabetes mellitus (t dm) (n = ; . ae . years). all completers were successful in losing weight (pre-post diff. . ae . kg) and showed a comparable weight reduction after intervention: females À . %, males À . %, ms/t dm patients À . %. the weight reduction was impressively accompanied by improvements of the metabolic milieu (tg, ldl-c, fbg, hba c) particularly in the ms/ t dm patients. the results confirm that the ipm concept is a successful way to lose weight initially and to improve the metabolic milieu within a shorttime period using a product with a high impact of bioactive compounds. objective: menopause-related changes in female body are associated with the greater risk of metabolic syndrome (ms), which includes obesity, dyslipidemia, impaired glucose tolerance, hypertension. the purpose of our study: was to reveal peculiarities of fat and lean mass distribution between postmenopausal women with abdominal obesity and with ms. design and method: the sample consisted of postmenopausal - years old women (age: mean = . ; sd = . ); duration of menopause: mean = . ; sd = . ). the diagnosis of ms was considered according to idf ( year) criteria. lean and fat mass distrubution were measured by dual-energy x-ray absortiometry, and were compared for the cohorts with and without ms. data were analyzed using statistical package . (statsoft). background and aims: attempts to curb the ongoing epidemic of obesity and diabetes in the us and other developed countries will benefit from better understanding of the broad and upstream determinants of the population prevalence of these conditions. this study explores how individual psychosocial characteristics in addition to the social and physical community environment correlate with prevalent obesity and markers of pre-diabetes in a statewide representative sample of the population of wisconsin, usa. methods: we used cross-sectional data from the to cycles of the ongoing survey of the health of wisconsin (show) a geographically diverse population-based research study of adults, age - years (n = ). obesity (bmi ! kg/m ) and hemoglobin a c levels were the main outcomes. independent variables included individual socioeconomic status (ses), food insecurity, psychosocial status (depression, anxiety and stress), perceived discrimination and neighborhood resources, and access to health are. contextual predictors included county and census-block group socioeconomic nutrition, and built environment indicators. results: the prevalence of obesity and prediabetes was positively associated with lower ses, food insecurity, markers of depression and anxiety, perceptions about lower access to healthy food and physical activity resources in the neighborhood, and poor health care access. lower community-level ses and a poor nutritional and built environment were also associated with higher frequency of obesity and prediabetes. conclusion: our findings on the psychosocial and contextual correlates of obesity and prediabetes offer insights regarding the profile of individuals and subgroups and where tailored individual and community level interventions are most needed. objective: gastric bypass (gbp) is currently the most effective way of treating obesity. interestingly, the majority of type diabetes (t d) patients display remission of the disease after gbp. the underlying mechanisms behind this remission are not known. we used a porcine model to study how hormonal and metobolite profiles are affected by gbp. in addition we studied the impact of gbp on endocrine cell populations in the gut and pancreatic islets. methods: gbp-pigs were subjected to oral (ogtt) and intravenous (ivgtt) glucose tolerance tests before and after surgery. shamoperated, pair-fed pigs served as controls. results: during ivgtt gbp-pigs displayed lower glucose and higher insulin levels compared to controls. during ogtt, gbp-pigs displayed higher glucose and a more rapid and robust insulin response than controls. in line with this, gbp-pigs had higher beta cell mass and more extra-islet beta cells. further, during ogtt gbp-pigs displayed robustly elevated gip levels, whereas glp- levels were unchanged. furthermore, gbp-pigs displayed elevated density of gipproducing k-cells, but reduced density of glp- -producing l-cells in the gut. metabolomic analyses revealed a difference in the metabolite pattern between the two groups, mainly explained by the fact that gbp provoked lower levels of free fatty acids (ffa) and higher levels of branch-chain amino acids (bcaa). conclusions: gbp in pigs provokes, . enhanced insulin secretion and increased beta cell mass. background: several authors have recently reported that both hiv replication and antiretroviral therapy (art) may influence adiponectin expresion which is correlated with insulin sensitivity via glucose transporter type recruitment to plasma membrane. we assessed serum adiponectin patterns in a cohort of hiv- positive caucasian patients undergoing cart in relation to insulin resistance (ir) and hiv replication. a cross-sectional study was performed in a cohort of hiv- infected patients attending the national institute of infectious diseases, bucharest. blood samples were tested for hiv viral load and adiponectin. insulin resistance was estimated by homoeostasis model assessment. in order to evaluate differences between groups we used mann-whitney-wilcoxon and t-tests. results: eighty patients ( . % males) with a median age of years (iqr years) were included in the study. the median time from hiv diagnosis was . months and the median time on cart was . months. most patients ( . %) had undetectable serum hiv loads. median adiponectin serum value was . lg/ml (iqr ). most patients ( . %) had insulin resistance. insulin resistant patients had significantly lower median levels of adiponectin ( . vs. . lg/ ml, p = . ). there were no significant differences between median adiponectin serum levels in groups with persistent and undetectable hiv replication (p = . ). no significant correlation was noted between insulin resistance and hiv replication. conclusions: in our cohort of young hiv- patients with a high prevalence of ir decreased adiponectin serum levels were associated with decreased insulin sensitivity. hiv replication may not influence in vivo adiponectin expression. objective: to examine obesity and metabolic disorders associated with vitd deficiency/insufficiency in children older people. methods: cross sectional study in community-dwelling subjects - year ( women) residing in santiago chile. plasma levels of (oh)d were determined by radioimmunoassay. glucose, insulin and crpus, were measured in a fasting blood sample. blood pressure and complete anthropometry were measured. results: mean serum (oh)d was . ae . nmol/l (men . ae . ; women . ae . , p < . ). (oh)d levels were under nmol/l in . % of men and . % of women (p = . ). insulin resistance was present in . % of all subjects and obesity in . % of women and . % of men (p < . ). significant negative crude association between (oh)d across bmi categories was found in the total sample (p < . ). crude association of vitd < nmol/l with obesity (p = . ), waist circumference (p = . ), insulin resistance (p < . ), metabolic syndrome (p = . ), hta (p < . ) and age ! year (p < . ) was observed. after age, sex, waist circumference and season adjustment, vitd < nmol/l was associated with increased risk of insulin resistance, or . (ic % . - . ) p = . . conclusion: high prevalence of vitd deficiency/insufficiency was observed in the chilean older people. vitd deficiency is associated with insulin resistance. in the future, randomized controlled trials are needed to establish a cause-effect relationship between vitd deficiency, obesity and its metabolic consequences. surrogate markers are used to estimate degree of steatosis and liver fibrosis in nafld. oxidative stress is important in the pathophysiology of nafld. the aim of this study is to find correlations between blood antioxidants and laboratory variables that are routinely determined in patients with nafld in clinical practice and used in fibrosis test. thirty-five obese children ( - years old) with increased liver echogenicity on ultrasounds and healthy lean children were enrolled. other causes of chronic hepatitis, such as chronic viral hepatitis, were excluded. erythrocyte superoxid dismutase (sod), glutathione peroxidase (gpx) activities and plasma levels for albumin, uric acid and bilirubin were measured as antioxidants. the nafld fibrosis score was calculated by an altgoritm including: age, bmi, glycaemia, platelet number, albumin, ast/alt. pearson correlations were calculated. none of the obese children had fibrosis according to the test score. obese children with nafld had lower levels for albumin (p < . ), but higher levels for uric acid (p < . ), sod and gpx activities (p < . ) vs. lean children. all the measured antioxidants were related with variables included in the fibrosis test. for p < . , the calculated correlations were: sod activity with alt activity (r = À . ) and albumin (r = . ), gpx activity with ast/alt ratio (r = . ), uric acid with alt activity, age and bmi (r = . ). this study demonstrates strong relations between blood antioxidant defence systems with fibrosis test variables in nafld in obese children. women; diabetes prevention programs (dpp) are only available for adults at high risk of developing t d. . to develop a dpp for post-gd women. . to assess the feasibility/acceptability of this dpp through a pilot rollout. methods: a working group was formed to develop a dpp that incorporated the needs of a mother with a young family around established lifestyle modification goals. this program was piloted with a group of nine post-gd women. the pilot had high attendance levels ( - % for group sessions), but only % of participants attended all sessions (illness and travel commitments causing non-attendance). the original magda dpp was restructured to: an individual session, five group sessions and two follow-up telephone conversations. childcare arrangements were investigated, but participants elected to have their children attend sessions. participants reported the program to be acceptable and suited to their needs. the pilot determined that the program was feasible and met the needs of the target population. currently, recruitment is underway for post-gd women from three hospital sites for the magda study, which uses a dpp designed for post-gd women and has a whole-of-family focus and tackles common barriers to success. objectives: assess the risk factors associated to physical inactivity (pi). a cross-sectional study was performed in in subjects aged ! years, in the urban area of montes claros, brazil. the physical inactivity level was determined by the international physical activity questionnaire short version. the subjects were classified in active ( ! min per week) and sedentary (< min per week). the univariate analysis was first performed and were included in the model when associated with p < . . the poisson regression with robust variance was realized and the prevalence ratio (pr)-crude and adjusted-and % confidence intervals (ci) were estimated to determine the relationship between pi and risk factors like sex, age group, skin color, marital status, income, education, hypertension, dyslipidemia and overweight. the variables that remained significant when adjusted. the statistic was performed in stata. results: a sample of individuals were studied ( . % women). the prevalence of pi was of . %. the variables were associated with pi were sex, the age group, marital status, education, hypertension, dyslipidemia and overweight with p < . . the following variables were significantly associated with pi after adjustment for confounding variables were: sex, female (rp = . ; ic: . - . ) and marital status, separated/divorced/widowed (rp = . ; ic: . - . ). the gender and marital status were associated with pi with pr higher for these variables in this population, which shows the need for development of effective public policies, integrated to investigate the biological causes, but also the social risk factors. objective: to determine whether an interactive mhealth exercise intervention is more effective than standard of care exercise in patients with metabolic syndrome. methods: participants [n = , mean age . (sd . ) year, % female] reported to the laboratory at baseline (v ) and follow-up [ (v ) and (v ) weeks]. anthropometrics, heart rate (hr) and blood pressure (bp) were measured and blood drawn to examine fasting glucose (fg) and glycated hemoglobin (hba c ). fitness (vo max ) was assessed and individualized exercise programs were prescribed. the intervention group received a smartphone data portal and bluetooth tm enabled biometric tracking. differences between groups in outcomes (v -v ) were examined using analyses of covariance, which adjusted for baseline levels of the outcome of interest. group differences from v to v were examined with two-way repeated measures anovas. results: at v , systolic bp was reduced in both groups but significantly more in the control group (difference in mean change: À . ; % ci: À . , À . , p = . ). there were no differences between groups at v for other outcomes. across the follow-up period, systolic bp, diastolic bp, resting hr, weight, body mass index, waist circumference and hba c were decreased, and vo max and target hr were increased for the entire study population (p < . ) with no difference in rate of change between groups. fg was significantly higher in the intervention group across the entire follow-up period (p = . ) and both groups had increasing levels over time (p = . ). conclusion: over weeks, cardio-metabolic risk factors improved with both standard and mhealth supported exercise interventions. background and aims: breastfeeding improves glucose tolerance in the early postpartum period of women with prior gestational diabetes (gdm), but it is unclear whether future risk of metabolic alterations, like type diabetes, is reduced. the aim of this study was to investigate the effect of lactation, years after pregnancy, on glucose metabolism and beta cell function in women with prior gdm. material and methods: women with prior gdm (carpenter and coustan criteria) were evaluated with comparison of results for "lactating" [bf] vs. "non lactating women" [non bf]. breastfeeding was defined exclusive if lasting more than weeks. each woman performed a -g ogtt to analyze glucose tolerance, insulin sensitivity/resistance and b-cell function. lipid and inflammatory profile was also studied. statistics: paired and un-paired t-test, mann-whitney and v tests. methods: subjects completed three randomly ordered conditions: mie ( % vo peak), hie ( % vo peak), and seated rest (control). exercise energy expenditure was equated to -kcal. one-hour postexercise (or control), subjects received a -g oral glucose tolerance test (ogtt). plasma glucose and insulin concentrations were measured before and at frequent intervals after glucose ingestion. si was derived using the following models (i) oral minimal model (omm), (ii) matsuda composite index, (iii) cederholm index, and (iv) stumvoll index. exercise induced changes in insulin action were expressed relative to the control condition (exercise-control). spearman correlation coefficients and rm-anova were used to compare relative changes in insulin sensitivity. results: si calculated during the control condition was moderately correlated among the various indices (r-value range: . - . , pvalues: . - . ). relative to control, si after mie ranged from % higher (cederholm) to % higher (omm), and after hie ranged from % lower (matsuda index) to % higher (omm excess caloric intake leads to metabolic overload and is associated with development of type diabetes (t dm). current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. we hypothesize that normalizing blood glucose levels by itself is insufficient to treat the disease and the development of complications, and that dietary interventions which diminish metabolic overload may be more efficacious in retarding the disease. we explored the efficacy and systems effects of pharmaceutical interventions vs. dietary lifestyle interventions (dli) in developing t dm and complications. high fat diet (hfd)-fed ldlr À/À mice with already established disease phenotype, to mimic the human situation, were treated with different drugs mixed into hfd or subjected to dli (switch to lowfat chow), for weeks. interventions were compared to untreated reference mice kept on hfd or chow only. although most of the drugs improved hfd-induced hyperglycemia, drugs only partially affected other risk factors and also had limited effect on disease progression towards microalbuminuria, hepatosteatosis and atherosclerosis. by contrast, dli normalized t dm risk factors, fully reversed hepatosteatosis and microalbuminuria, and attenuated atherosclerosis. the comprehensive beneficial effect of dli was reflected by normalized metabolite profiles in plasma and liver. analysis of disease pathways in liver confirmed reversion of the metabolic distortions with dli. this study demonstrates that the pathogenesis of t dm towards complications is reversible with dli and highlights the differential effects of current pharmacotherapies and their limitation to resolve the disease. introduction: obesity may induce an oxidative stress in adipose tissue, leading to deregulated expression of inflammatory cytokines which could be an early instigator of obesity-associated diabetes and cardiovascular diseases. thus, the biological effect of natural micronutrients such as plant polyphenols that may increase the antioxidant capacity of the body is of high interest. aim: our objective was to explore the antioxidant polyphenol content of three medicinal plants (gouania mauritiana, antirhea borbonica, doratoxylon apetalum) and their impact on the viability, production of reactive oxygen species (ros) and inflammatory response of preadipocytes exposed to oxidative stress. methods: polyphenol-rich extracts from plants were analyzed for their radical-scavenging capacity by dpph method. then, their ability to modulate t -l preadipocyte viability and protection against h o induced oxidative stress was assessed by both mtt viability and ldh death assays, as well as by dcfh-da test evaluating intracellular ros production. finally, il- secretion was measured by elisa. results: all plant extracts exhibited high levels of antioxidant polyphenols which protected preadipocytes against oxidative stress by decreasing ros generation and modulating the inflammatory response. such an antioxidant activity of plant extracts could be partly mediated through their radical-scavenging capacity. we identified three medicinal plants naturally rich in antioxidant polyphenols which exerted antioxidant and antiinflammatory properties on preadipocytes exposed to oxidative stress. further studies are in progress to clarify the molecular mechanism as well as in vivo potential effects of such medicinal plants to protect against metabolic and inflammatory disorders known to play a key role in obesity-related insulin resistance. background: increased fasting plasma glucose is known to lead to diabetes, and diabetes associated complications often manifesting prior to the identification of type diabetes. we aimed to determine the association of fasting plasma glucose levels with cholesterol levels and oxidative stress markers. methods: one hundred and sixty two participants attended the diabetes screening clinic, at charles sturt university, australia between february and june . participants were investigated based on the american diabetes association′s diagnostic criteria of diabetes mellitus and prediabetes, i.e. fasting bgl. results: atherogenic index of plasma (aip) was elevated in the prediabetes group ( . ae . ) and continued to increase in the diabetes group ( . ae . ) compared to controls (À . ae . ; p < . ). serum -hydroxy- -deoxy-guanosine ( -ohdg) level was greater in the prediabetes ( . ae . pg/ml) compared to controls ( . ae . pg/ml; p < . ). the diabetes group ( . ae . pg/ml) had the highest level of -ohdg. these changes paralleled by a reduction in erythrocyte reduced glutathione (gsh) from controls ( . ae mg/ ml, p < . ) to prediabetes ( . ae mg/ ml; p < . ) and the diabetes group ( . ae . mg/ ml, p < . ). conclusion: this increase in -ohdg may be related to the decrease in erythrocyte gsh antioxidant capacity. a statistical significant positive correlation (pearson's r = . ; p < . ) between aip and -ohdg suggests that -ohdg may be a useful additional biomarker to determine the degree atherogenic risk in the presence of elevated lipids. rowett institute of nutrition and health, university of aberdeen, aberdeen, uk, ilsi europe, brussels, belgium, lund university, lund, sweden, mechanistic evidence suggests that elevated blood glucose levels contribute to the development of t dm. adoption of a nutritional approach to manage postprandial glycaemia could deliver a cost-effective t dm prevention and management strategy, applicable across the population. to implement a successful strategy it is essential to understand the impact of dietary modulation on the postprandial rise in blood glucose concentrations. for this reason, a systematic and comprehensive literature review was undertaken, using the highest quality data. included were the major macronutrients (carbohydrate, protein, fat), micronutrient vitamins and minerals, non-nutrient phytochemicals and additional foods including low-calorie sweeteners, vinegar and alcohol. the strongest corroboration of efficacy for improving glucose homeostasis was for insoluble and moderately fermentable cereal-based fibre and monounsaturated fatty acids as replacement of saturated fat. postprandial glucose levels were decreased by intake of viscous soluble fibre and this was considered to be predominantly by delaying absorption of coingested carbohydrates. weaker but substantial evidence demonstrated that certain phytochemical-rich foods were likely to be effective and this may be associated with the suggestion that the gut microbiota plays an important role in metabolic regulation, including provision of phytochemical and other metabolites. it is clear that dietary components have significant and clinically relevant effects on blood glucose modulation. this suggests that employing a dietary regimen to attenuate the postprandial rise in blood glucose levels along with previously identified targets (reducing excess body weight and an increase in physical activity) will benefit the health of the population and limit the increasing worldwide incidence of t dm. knowing their metabolic control, and lipid profile, through an early intervention, we can reduce their risk factors for cardiovascular disease, and diabetes complications. the aim of our study was to determine the lipid profile of patients newly diagnosed with type diabetes. patients and methods: hundred patients, selected at the outpatient policlinic nr. in tirana, the capital of albania. all the patients had completed anthropometric measures, hba c and lipid profile after a -h fast. the persons younger than years, diabetes diagnosed prior to months, or uncompleted data were excluded from the study. results: we obtained all the data for patients. males ( %), mean age . ae . years, mean bmi . ae . kg/m², mean hba c . ae . %. . % of the patients had a total cholesterol > mg/dl, % of the patients had triglycerides > mg/dl, and . % of them had tg < mg/dl, and % had the ldl > mg/ dl . % of males had hdl < mg/dl and % of women had hdl < mg/dl respectively. conclusions: in our study the lipid profile of albanian patients was somehow different from the common profile of patients newly diagnosed with t diabetes. even in the previous studies we have found a lipid profile with high total cholesterol levels, and especially very low hdl levels, probably due to the sedentary lifestyle, which needs further evaluation, because the metabolic control of our patients was not very bad. background and aims: physical activity (pa) in people with type diabetes helps to improve metabolic control, lipid profile, and to reduce weight. the aim of our study was to demonstrate the effect of a single session of pa to the glycaemic profile, and the effect of increasing daily physical activity on the weight and lipid profile. patients and method: fifty patients were recruited for a weeks training session. every pa session lasted min of fast walking. the number of daily steps was measured through a pedometer, and all the participants were encouraged to complete at least , steps/day. all the patients had completed anthropometric measures, fat body composition and lipid profile at the beginning and the end of study period. background: homocysteine is a cardiovascular risk factor for the development of vascular pathology. large population studies have been conducted demonstrating a positive association between homocysteine levels and risk of developing cardiovascular disease. paradoxically in type diabetes, if renal function is within a normal range, homocysteine levels are either similar or reduced when compared to levels in the normal non-diabetic population. whether the same is true for pre-diabetes has not been previously explored. our study examines the plasma levels of homocysteine in controls, and participants with prediabetes and diabetes from a screening program in regional new south wales. methods: seven hundred and forty-four participants attended the diabetes screening clinic, at charles sturt university, australia. participants were investigated based on the american diabetes association′s diagnostic criteria of diabetes mellitus and prediabetes, i.e. fasting blood sugar levels. venous plasma homocysteine samples were measured using the fluorescence polarization immunoassay on the imx â analyzer (abbott laboratories, abbott park, il). results: median age across the three groups ranged from to years. the median levels for plasma homocysteine between groups were not significantly different. there was a trend for plasma homocysteine (μmol/l) levels to be higher in the prediabetic group . ae . (sd) compared to the control group with . ae . (sd) and in the diabetic group of . ae . (sd). conclusion: there is a non-significant median increase in homocysteine in the pre-diabetes group. further larger cross-sectional population studies would be able to address whether this is a chance effect and also establish statistical significance if present. clinical endocrinology, institute for endocrine pathology problems, kharkiv, ukraine introduction: active acromegaly is associated with increased morbidity attributed by systemic complications such as carbohydrate dysfunction. aims: to evaluate the effects of chronic excess of gh and igf-i on prevalence and structure of carbohydrate dysfunction in patients with active acromegaly. subjects and methods: ninety-seven patients ( men and women; aged - years) with macroadenoma of hypophysis ( somatotropinoma, -somatomammo-tropinoma) were under investigation. blood samples for gh, igf- , immuno-reactive insulin (iri), glucose were taken in fasting state and on min ottg. insulin sensitivity and b-cell function were estimated by homa calculator v. . data are given as m ae se and coefficient of determination (r ) of multiple regression analysis. results: in . % of patients with acromegalia (gh - . ae . ng/ ml; igf- - . ae . ng/ml) different types of carbohydrate dysfunctions (cd) were found out: fasting hyperglycemia ( . %); impaired glucose tolerance ( . %), and diabetes mellitus ( . %). . % of patients have had hyperinsulinemic state. it was no sex differences in the cd structure. iri level was . ae . mu/ml, insulin sensitivity - . ae . %, β-cell activity - . ae . %. homa _ir was positively associated with gh (r = . %, p = . ) and igf- (r = . %, p = . ). homa _b% was positively associated with gh (r = . %, p = . ) and igf- (r = . %, p = . ), and negatively with disease duration (r = . %, p = . ). the gh hypersecretion and length of its pathologic action predetermine the stage of carbohydrate dysfunction from fasting hyperglycemia, impaired glucose tolerance to overt diabetes mellitus. a. vlassopoulos, m. lean, e. combet human nutrition, school of medicine, university of glasgow, glasgow, uk background: protein glycation is a key mechanism behind chronic diseases in both diabetic and non-diabetic individuals. about - % of circulating proteins are glycated in vivo in normoglycaemic blood, but in-vitro studies have hitherto failed to demonstrate glucose-driven glycation below concentration of mmol/l. methods: albumin, mercaptalbumin ( g/l) and plasma was incubated with glucose at different concentrations ( - mmol/l) for weeks at °c. to investigate the effect of oxidation on protein glycation, all protein models were used as native proteins or oxidized proteins (exposed to nmol/l h for h prior to incubation with glucose and throughout the incubation period). fructosamine was measured at and weeks (nitroblue tetrazolium method). oxidised mercaptalbumin and plasma had higher fructosamine concentrations at weeks at mmol/l glucose compared to native controls (p < . ). at mmol/l glucose, the same effect was observed for albumin and mercaptalbumin but not plasma. only oxidized albumin was significantly glycated at weeks with mmol/l glucose (compared to glucose-free control) when native was not. at weeks no effect of oxidation was observed. the current study has for the first time demonstrated the importance of oxidative stress in physiological protein glycation, interacting with glucose and promoting glycation in the early stages of the process. k. elksne , z. paunina , a. jurka , d. rezeberga , p. tretjakovs obstetrics and gynecology, physiology, rigas stradins university, riga, latvia introduction: a growing number of obese women in their reproductive years increases their risk for obstetric complications, but still the exact mechanisms is not known. we created a prospective study in which clinical data were collected from antenatal visits in pregnant women. obstetric outcomes were assessed at delivery. obstetrical outcomes depending on fetal macrosomia and maternal bmi were analysed using the fisher exact test. relationships between pre-pregnacy bmi, gestational weight gain and fetal weight were analysed using spearman rank correlations. results: overweight women had lower total weight gain during pregnancy, but higher risk for obstetric complications such as fetal macrosomia, uterine dysfunction, ceasarean section and ruptures of the birth canal. fetal macrosomia positively correlated with pre-pregnancy weight, but not with gestational weight gain during pregnancy. also male gender is a risk factor for birth weight above g. it is important to increase the number of planned pregnancies, pre-pregnancy visits to doctor in order to inform women about the impact of excess weight on perinatal outcome as fetal macrosomia is associated with impaired maternal bmi. women with bmi normal before pregnancy increased their weight above recommendations during gestation. as excessive weight gain may be a risk factor for long term complications, more information about diet should be provided in antenatal visits. obesity and fetal macrosomia correlate with complications during labour, so additional attention in birth conducting should be paid. background: the obesity epidemic is widely blamed for the rise in type diabetes, but new research suggests it is also linked to the increase in type diabetes (t d). the combination of obesity and t d has a negative impact on metabolic control in patients with t d in particular during pregnancy. aim: to evaluate the rate of overweight or obese women with t d at pregnancy onset according to their body mass index (bmi) and its relation to metabolic control. we performed an analysis of singleton pregnancies of women with t d, who consulted our diabetes outpatient clinic since . results: all women were caucasians with mean age of ae years and average diabetes duration of ae years. only % of all women with t d had a bmi of < kg/m , % were overweight with bmi between . % and . % and % were obese. the metabolic control was similar between the group with normal bmi and bmi > kg/m ( . ae . % vs. . ae . %). in the patients with normal bmi only % started the pregnancy with a hba c < %, which was mainly due to unplanned pregnancies. conclusion: our data revealed a high proportion of overweight women with t d at onset of their pregnancy, confirming the worldwide trend of rising obesity rates and which calls for preventive measures in the preconception counseling. hypertension is more prevalent in hivinfected subjects than in general population, contributing to increased cardiovascular risk in hiv+ patients. moreover, hiv patients more frequently showed metabolic alteration than general population. aim of this study was to evaluate the effect of weeks of administration with telmisartan mg daily in hiv+ patients. we enrolled hiv+ caucasian male patients treated with combined antiretroviral therapy (cart) and discovered to be na€ ıve hypertensive. systolic (sbp) and diastolic (dbp) blood pressure, viro immunological parameters and triglycerides, cholesterol, insulin resistance (homa-ir), inflammatory markers, c-reactive protein (crp), indexes of renal function and cardiovascular risk, microalbuminuria, cystatin c, were measured at baseline (t ), and after (t ), (t ), (t ), (t ), (t ) and (t ) weeks. treatment with telmisartan decreased sbp and dbp levels during the weeks of observation. we also observed improved in totalcholesterol, triglycerides, and in total cholesterol/hdl cholesterol ratio. we also observed an microalbuminuria and cystatin c improvement at the end of study. throughout in the course of the trial our patients showed a significant improvement of the percentage of cd + and cd . telmisartan doesn't interfere with the recovery of immunological parameters in this patients. telmisartan has confirmed durability and effectiveness, excellent tolerability and an high persistance with a good blood pressure control. therefore telmisartan should be the first choice in the treatment of hypertension in hiv+. methods: the subjects studied were patients diagnosed with gdm at ska˚ne university hospital, lund, sweden, - . sera were analyzed for antibody positivity (gada, ia- a and znt a) with commercially available elisa and snps were studied with restriction fragment length polymorphism. results: combinations of two or more autoantibodies ( . %) were less frequent than single positivity for gada ( . %) or znt a ( . %), but not ia- a ( . %). patients that developed t d postpartum often had combinations of autoantibodies. heterozygosity for r w was increased ( %) in patients that developed znt a compared to znt a negative patients ( %). however this was not statistically significant (p = . ). conclusions: the previously reported prevalence of znt a in gdm was confirmed. positivity for znt a did not seem to be a good independent predictor for development of t d. the tendency of increased r w heterozygosity in znt a positive gdm patients is a novel finding and of interest since the snp has been suggested to be of importance in both t d and t d. among several consequences, obesity seems to have detrimental effects on reproductive function, causing low levels of sex hormones and reduced sperm concentration. the excess of lipids on diet influences metabolism and affects testis reproductive function. the relationship between obesity, reproductive changes and metabolic syndrome is not yet fully clarified. thus, the aim of the study was evaluate the effect of high fat diet, containing soybean oil, on body composition and male reproductive system of young rats. wistar rats, at days, received diet containing % (control diet) or % (high fat diet, hf) of soybean oil, until and days of age. food intake and body mass were monitored. at the end, body composition was evaluated by dexa and blood, liver, adipose tissue, testis and epidydimis were collected. glucose, triglycerides, cholesterol, hdl, vldl, insulin and leptin were measured. food intake, body mass gain, lean mass, total fat mass and bone mineral content did not differ between the groups at and days. at days, glycemia and epidydimal adipose tissue mass were increased in rats fed with hf. at days, glycemia, leptinemia and the mass of mesenteric adipose tissue, liver and epidydimis were high after hf ingestion, while tg was low. the excess of lipids reflected negatively on intra-abdominal adipose tissue since days, accompanied by hyperglycemia. the hf ingestion maintained high glucose and leptin concentrations without insulin alteration. at the same time, it could predict some testis function change, once epidydimis mass increased in these young animals. adipose tissue is linked to cardio-vascular and metabolic complications of obesity by increased local production of adipokines.to investigate serum levels of adipokines (adiponectin and leptin) and relationship with obesity anthropometric markers and insulin resistance in overweight/obese patients with type diabetes. two groups of subjects were selected: group with type diabetes mellitus (n = ) and control group (n = ). the first group was subdivided in two subgroups, according with bmi (overweight and obese). in all individuals were assessed bmi, waist and hip circumference, visceral fat index, serum levels of adiponectin, leptin, insulin and proinsulin and homa-ir was calculated. the determined parameters were modified significantly in the diabetic patients vs. control. comparing the obese diabetic patients with the overweight, serum levels of leptin were higher on obese/overweight (p < . ) and levels of adiponectin were lower (p < . ). also, serum levels of insulin and proinsulin were higher in diabetic vs. control group maintained their statistical significance difference in the subgroups of overweight/obese (p < . and, respectively, p < . ). bmi was positively correlated with leptin (p < . ) and adiponectin negatively (p < . ). moreover, leptin was positively correlated with visceral fat index (p < . ), waist circumference (p < . ) and homa-ir (p < . ); adiponectin was negatively correlated with waist circumference (p < . ), visceral fat index (p < . ) and homa-ir (p < . ). in conclusion positive correlation (leptin) and negative (adiponectin) with anthropometric markers of obesity and homa-ir, demonstrating the role of adipokines in the pathogenesis of peripheral insulin resistance in patients with "diabesity." materials and methods: based on research institute of nutrition we randomly chose patients with varying class obesity, who were outpatient for this disease. all patients were tested on the personal scale manifestations of anxiety (d. teylor in adapting t. nemchina). patients were asked to read a set of sentences ( questions) about their traits. if they agreed with the statement they should answer "yes" if they did not agree -"no". the test had a ball-evaluation, in which anxiety is defined as very high, high, medium and low. objectives: the process of converting prediabetes to diabetes remains a matter of debate. the aim of the study was to assess insulin sensitivity/resistance indices and markers of oxidative stress in prediabetic persons. methods: obese non-smoking caucasians, using neither special diet nor medication, without acute and chronic disorders, were qualified for ogtt and assigned to groups: normal glucose tolerance-ngt, impaired fasting glycemia-ifg, impaired glucose tolerance-igt and newly diagnosed type diabetes-t dm, each group n = subjects: f/ m; age : - (median: quartiles - ). plasma glucose (siemens) and insulin (biosource) were determined during ogtt ( ', '). plasma total antioxidant status-tas (randox), thiobarbituric acid-reacting substances-tbars (sigma), lipids and hscrp (siemens), as well as hba c (hplc) were assayed fasting. different indices of insulin sensitivity/resistance, fasting steady-state and derived from ogtt, were calculated. results: the groups did not differ according to age, bmi, waist, blood pressure, lipids and hscrp. insulin sensitivity/resistance indices presented variety of sensitivities and specificities for prediction of dysglycaemia categories, as well as different correlations with metabolic parameters, including oxidative stress, i.e. isi , &tas (r = . ), isi , &tbars (r = À . ) in the population n = . the comparison of ngt-ifg-igt-t dm, showed the highest tas in ifg and the lowest in t dm (p = . ), together with increasing tbars from ngt to t dm (p = . ). the results of roc curves analysis pointed isi , ( % sensitivity; % specificity) for prediction of igt, and tas ( % sensitivity; % specificity) in differentiation between igt and t dm. conclusions: insulin-sensitivity indices predict prediabetes in obese subjects near perfectly, while the development of diabetes is preceded by antioxidant insufficiency rather. m. smiraglia , g. bott a , e. orsi endocrinology and diabetolgy, fondazione ca' granda irccs -ospedale maggiore policlinico di milano, biomolecular sciences and biotechnology, university of milan, milan, italy t dm is a metabolic disorder and evidences show that medical nutrition therapy improving glucose metabolism reducing the risk of complications, leads to an improvement in life quality and increase life expectancy. the aims of diabetes management are normalize blood glucose levels and weight control. obesity influences the development of t dm and complicates its management. the study aim was to value the effect of two different nutritional treatments (nt) on the anthropometric parameters and glucose metabolism in patients with t dm and obesity. the two nt are: the "low gi diet" that promotes the carbohydrates quality and the food choice is made on the glycemic index; the "low-carbohydrate diet" is based on the concept that glucose metabolism is influenced also by the carbohydrates amount. subjects, selected on including and excluding criteria, were randomly divided in two groups, to each of which one of the two nt was assigned. during the study participants were measured three times. all statistic differences in the values were analyzed with the use of anova test. the "low-gi group" showed a significant decrease in hba c (À . %; p = . ). data suggest that this nt positively influences the glycemic control. the "low-carb group" showed a significant decrease in insulin level (À . %; p = . ), a greater reduction in bmi and whr and a homa-insulin resistance index reduction (À . %; p = . ). the daily reduction of carbohydrate intake influenced positively the blood glucose response and significantly reduced plasmatic insulin levels. data suggest that either nt improves glycemic control and peripheral insulin sensitivity. aims of study: the use of metformin to control glucose in pregnant women with gestational diabetes mellitus (gdm) to evaluate its safty use during the first trimester of pregnancy. design: cases report of four patients with gdm from the first trimester of pregnancy non smoking with no family history of congenital malformation disease, aged between ( and ) and have no liver diseases put on metformin were participated in this study and who had indicating good comliance at more than one visit over several month until delivery. result: all four patient in oure study delivered healthy babies. internal medicine, ist medical clinic, umf iuliu hatieganu cluj-napoca, immunology laboratory, emergency county clinical hospital, cluj-napoca, romania introduction: the potential role of oxidative stress (os) in metabolic syndrome (mets) is rapidly evolving. reported results support the concept that increased os may play a key role in the development of atherosclerosis, hypertension and diabetes. study aim: the purpose of the present study was to analyze the impact of mets and its individual components on os and on the antioxidant status. material and methods: seventy-two hospitalized patients with a mean age . ae . years were taken under study between october and june . mets was diagnosed based on aha/nhlbi/idf definition. os was assessed by urinary iso-prostaglandinf a ( iso-pgf a) (immunometric assays) and plasmatic uric acid. antioxidant status was evaluated by plasmatic gluthatione peroxidase (gpx). these data were compared to those of biologically and clinically healthy subjects (mean age . ae . years). results: all biomarkers were significantly higher in mets patients as compared with healthy individuals (p < . ), except gpx which was significantly lower (p < . ). gpx and uric acid were statistically significant correlated. in multivariate analysis iso-pgf a concentrations were influenced by hypertension, fasting glucose and triglycerides, uric acid levels were directly influenced by hypertension, waist circumference, fasting glucose and triglycerides. gpx levels were inversely correlated with blood pressure (all p < . ). only gpx was influenced by the number of mets components. objective: the purpose of this study was to compare changes in the plasma metabolome during an intravenous glucose tolerance test (ivgtt) among persons with low or high insulin sensitivity (si < . or > . ). methods: ivgtts were performed in men and women, ae years, with low si ( . ae . ) and men and women, ae years, with high si ( . ae . ). targeted electrospray ionization, tandem mass spectrometry was used to measure plasma concentrations of amino acids and acylcarnitines during the first phase of the ivgtt. other metabolites (glucose, insulin, etc.) were measured by conventional methods. results: fasting glucose, insulin, triglycerides, glycerol, free fatty acids, leucine/isoleucine, tyrosine, glutamate/glutamine, -hydroxypalmitoleylcarnitine (c : -oh)/dicarboxytetradecanoylcarnitine (c : -dc), and docosanoylcarnitine (c ) were significantly higher in the low si group, whereas ornithine was significantly lower. in response to glucose infusion, rates of disappearance of alanine, proline, valine, leucine/ isoleucine, methionine, and phenylalanine were %, %, %, %, %, and % lower, respectively, in the low si group. there were no group differences in changes in circulating concentrations of free fatty acids, glycerol, triglycerides, or acylcarnitines. conclusions: insulin resistance is associated with lower rates of disappearance of neutral, non-polar amino acids during the first phase of the ivgtt, suggesting insulin-mediated clearance of amino acids and/or suppression of protein catabolism may be impaired. cigarette smoking is worrisome in adults and also in adolescents. actually, smoking rates have grown, especially among girls, and little is known about the damages caused in these organisms still young or the consequences in adulthood. this study aim evaluates the influence of smoking in puberty and the consequences of withdrawal, body composition of female and male mice. at days, mice were exposed to r f cigarette (tobacco and health research institute) smoke, h/day for days (s, n = ). then, half of animals were evaluated and the other half was maintained and evaluated days after stop exposure ( d as). an unexposed group accompanied the events (ns, n = ). body mass, body composition (dexa), food intake, blood, ipgtt and adipose tissue were evaluated. during exposure food intake was similar all groups, however, s groups showed low body mass gain. das, s groups increased body mass and food intake in females. no alterations body composition were in males, while in females, increased total body and trunk fat during exposure and lean mass das. fat was high epidydimal and retroperitoneal in females. in regard blood, males did not alter insulin or ipgtt during exposure whilst females had high insulin levels and glycemia at min. withdrawal induced in males, high insulin and low glycemia the ipgtt and in females normal insulin and low glycemia. the set of results indicates different response cigarette smoke in young that seem to start in females and lead malefic metabolic alterations in adulthood. methods: this retrospective study included children and youths ( boys) from the children's obesity clinic. data were measured at the time for inclusion and included values of body mass index (bmi) standard deviation score (sds), blood pressure, gender, and biochemical measures, including the fasting concentrations of blood glucose, serum insulin, hba c, and serum lipids. the bmi sds was median . (range . - . ) and the age was median . (range . - . ) years. prediabetes was classified as a fasting blood glucose ! . and < . mmol/l. the mann-whitney-wilcoxon test was used for the analyses. results: prediabetes was present in ( boys) patients. these patients were older, age median . vs. . years (p = . ), had a higher bmi sds median . vs. . (p = . ), an increased fasting hba c median vs. mmol/mol (p < . ), an increased fasting serum insulin median . vs. pmol/l (p < . ), and an increased median homa-ir . vs. . (p < . ), respectively, compared to the patients with a fasting plasma glucose < . mmol/l. no differences were found in any of their fasting serum lipid levels or blood pressure (p > . ). in this large group of overweight and obese children prediabetes is prevalent. thus it seems important to identify obese subjects with prediabetes in order to prevent development of diabetes during childhood. introduction: epidemiological spreading of diabetes and developing in early age urge for finding causes and prevention before manifestation. aim of the study was testing accelerator hypothesis t. wilkin and colleges. method: the study is combined retrospective prospective. we examined history and follow up till age of years children who were referred to pediatrician endocrinologist because of obesity or diabetes. results: children from obese mothers and children with lower birth weight have more metabolic disturbances (insulin resistance, neonatal hypoglycemia, obesity, diabetes, precocious puberty, menstrual irregularity). subjects and methods: twenty-two obese women (bmi ae kg/m ) were followed during di that consisted of a days′ very-low-caloriediet (vlcd) and subsequent months low-calorie-diet followed by a months′ weight maintenance diet (wm). mrna expressions of adipokines (leptin, adiponektin, interleukines (il) - ,- ,- , tnfa, macrophage-chemoattractant-protein (mcp- ), haptoglobin) were measured, using rt-pcr, in samples obtained from abdominal scat at baseline and at the end of vlcd and wm, respectively. results: body weight (bw) and plasma crp decreased during vlcd and at the end of wm (bw: . ae . vs. . ae . vs. . ae . kg (p < . ), crp: . ae . vs. . ae . vs. . ae . mg/l (p < . ), respectively). the decrease of plasma crp during the entire months′ di correlated positively with the decreases of mrna expression of mcp- . (r = . , p < . ) and il- (r = . , p < . ) during the entire di and with the decrease of leptin mrna during initial vlcd (r = . , p < . ). no correlations were found for other adipokines. objective: to determine associations between change in lean body mass (lbm), fat mass and muscle strength with is following month of resistance training in obese postmenopausal women. methods: thirty-four ( with and without metabolic syndrome) non-diabetic obese postmenopausal were recruited. participants completed a month resistance training program ( times/week). body composition (dxa), handgrip strength and quadriceps strength were measured. fasting glucose and insulin levels as well as ogtt derived is indices (stumvoll, matsuda) and homa were also measured. non parametric correlations were performed with spss ( . ). results: significant increases in muscle strength, is and lbm as well as decreases in fat mass were observed after the intervention. however, no correlations were observed between changes in is with changes in muscle strength, lbm or fat mass in all participants as well as in subjects with or without the metabolic syndrome. conclusion: our results suggest that the changes in muscle strength, lbm and fat mass may not be associated with changes of is in obese postmenopausal women. therefore, other potential variables seem to be implicated in the changes of is in our cohort. objective: to examine the relation between total work (tw) performed and total heart rate work performed (trimps) with changes in cardiometabolic risk factors after resistance training in obese postmenopausal women. methods: thirty seven postmenopausal women (age: ae . , bmi: . ae . ) completed a month resistance training program ( times/week). body composition (dxa), blood pressure, metabolic risk factors (insulin sensitivity, h glucose, lipid profile and crp) and muscle strength were measured before and after the intervention. moreover, tw was calculated in each session by multiplying the number of repetitions, sets, weight and range of motion. thereafter, we added all training sessions. a heart rate monitor was used to assess trimps during each session. subjects were also categorized into two groups based on the top or lower th percentile of tw and trimps (high (n = ) vs. low (n = )). results: we showed that tw negatively correlated with systolic blood pressure and h glucose levels (p < . ). in addition, crp was negatively associated with trimps (p < . ). furthermore, high workers had lower levels of fat mass percentage and h glucose as well as higher lean body mass content than low workers. as for the high trimps group, we observed lower levels of crp compared to the low tripms group (p < . ). conclusion: results indicate that the quantity of work performed during resistance training is associated with better changes in metabolic risk factors in obese postmenopausal women. research design and methods: this cross sectional study included gestational diabetes patients who were diagnosed with gdm by a g ogtt and who underwent a standardized mixed meal tolerance test (mmtt). patients were divided into three groups according to the number of abnormal hyperglycemic values (group i for values, group ii for values, and group iii for values). glycemic parameters were compared to assess glycemic control (glucose, a c, ga) and gluco-metabolic homeostasis (homa-β, homa-ir). results: a total of gdm patients were recruited for this study. subjects whit a greater number of hyperglycemic values were also more hypertensive and obese, and had decreased insulin secretory functions than those with a lower number of hyperglycemic values (lnhoma-β, . ae . vs. . ae . , . ae . , p < . ). those with higher hyperglycemic values tended to have increased insulin resistance, but this result was not significant (lnhoma-ir, . ae . vs. . ae . , . ae . , p = . ). lnhoma-β correlated negatively with fasting glucose, a c, ga and ga/a c. multivariable regression analysis revealed that age and ga were significant independent predictors for lnhoma-β (standardized β = À . , À . , respectively, p < . ) but not a c. conclusions: korean women with dysfunctional pancreatic β-cells and increased insulin resistance are prone to gestational diabetes. ga, but not a c, is significantly correlated with pancreatic β-cell function. conclusion: altered adipokine profile is associated with increased cvd risk in pcos patients. these markers can serve as potential therapeutic target for decreasing their cv risk. objective: to determine the prevalence and determinants of nonalcoholic fatty liver disease (nafld) in a sample of adult iranian general population. method: this was a cross-sectional study being performed in shiraz, southern iran during a -month period from november to september through cluster random sampling of iranian general population in shiraz region. all individuals underwent anthropometric and blood pressure measurements and thorough medical history and physical examinations. laboratory measurements included fasting blood glucose (fbs), lipid profile, complete blood count (cbc) and liver function tests. nafld was diagnosed by transabdominal ultrasonography. result: overall we included subjects in this study among which there were males ( . %) and females ( . %) with the mean age of . ae . years. nafld was diagnosed in ( . %) subjects. patients with nafld were significantly older (p < . ), had higher proportion of male gender (p = . ) and had higher bmi (p < . ). they also had higher prevalence of hypertension (p < . ), high fbs (p < . ), high cholesterol (p = . ), high triglyceride (p < . ) and high waist circumference (p < . ). taking all these together, patients with nafld had significantly higher prevalence of metabolic syndrome when compared to healthy subjects (p < . ). conclusion: the prevalence of nafld in this group of iranian adult general population is . %. nafld in iranian population is associated with male gender, old age, obesity, and features of metabolic syndrome. a. othman , t. hornemann university hospital zü rich, clinical chemistry, university hospital zü rich, zü rich, switzerland -deoxysphingolipds (dsl) are atypical and neurotoxic sphingolipids which are formed by the enzyme serine-palmitoyltransferase (spt) due to a promiscuous use of l-alanine over its canonical substrate l-serine. pathologically elevated dsl levels were identified as a cause for the rare and inherited sensory neuropathy hsaniwhich is associated with several missense mutations in spt. significantly elevated dsl levels were also found in patients with mets or t dm as demonstrated in various clinical studies. principal component analysis identified the dsls as important descriptors for the mets statecomparable to triglycerides and superior to conventional mets biomarkers like fasting glucose or wcf. partial correlation analysis showed an independent correlation to plasma glucose and triglycerides. strikingly, recent data from prospective clinical studies identified plasma dsls as highly significant and independent predictors for the risk to develop t dm. elevated dsl levels were also confirmed in plasma and liver of stz rats. the dsls are therefore clinically relevant blood biomarkers for an impaired glucose homeostasis but might also be directly involved in the pathology of diabetes related sequelae. like observed in hsan the -dsl formation is significantly suppressed in response to an oral l-serine supplementation. feeding an l-serine enriched diet to stz rats resulted in a significant reduction of plasma dsls, a significant improvement of neuropathic symptoms and reduced cataract formation. our findings strongly support the value of dsls as novel and clinically relevant biomarkers in mets and t dm but also as therapeutic targets for the treatment of the diabetic neuropathy and other sequelae. objectives: prevention of cardiovascular disease focused on the early stages of atherosclerosis, including endothelial dysfunction, should arouse attention of clinicians in dysglycaemia patients especially. the aim of the study was to assess plasma e-selectin concentrations in newly diagnosed type diabetes (t dm) and in t dm patients treated with metformin, comparing with normoglycaemic individuals. material and methods: excess body mass non-smoking males and females, - years old, presented with neither acute nor chronic disease, were enrolled into the study. oral glucose tolerance test (ogtt) was performed to find normal glucose tolerance, group- (n = , age: median ; interquartile range - ) and newly diagnosed t dm, group- (n = , age: ; - ). group- consisted of t dm patients who take medication (metformin) for at least year (n = , age: ; - ) and present no retinopathy, nephropathy and neuropathy, as well as no history of coronary incident or stroke. all participants were measured plasma glucose (g- , g- ), fasting lipids and insulin, and hba c level. e-selectin concentration in plasma was assessed using elisa method (r&dsystems). data are shown as median and interquartile range. results: groups - - did not differ in respect to their age and bmi. the comparison among groups, followed by post hoc analysis, revealed different (p = . ) e-selectin concentrations, ng/ml: group- : . ( . - . ), group- : . ( . - . ), group- : . ( . - . ). in combined group + (n = ) the correlation e-selectin&g- ' was observed independently from bmi and triglycerides (multiple regression β = . ; r = . ; p = . ). conclusion: metformin therapy may limit early stages of atherosclerosis in t dm patients not only works to decrease plasma glucose. aim: to evaluation clinical efficacy of candesartan and its effect on parameters of vascular elasticity, lipid profile, lipid peroxidation and antioxidative protection against a background of single-candesartan therapy in females with arterial hypertension (ah) and abdominal obesity (ao) during menopause. methods: forty-six patients were divided into two groups. group ( subjects) were given candesartan and group ( subjects)enalapril. twenty-four hour blood pressure monitoring (bpm), pulse wave velocity; plasma lipids, diene conjugates (dc), malonic dialdehyde, superoxide dismutase (sod) and homocysteine, uric acid were estimated. the dynamics of all parameters was evaluated initially and in weeks. results: candesartan is a more effective hypertensive drug that has a valid effect on the readings of systolic blood pressure (sbp) and diastolic blood pressure (dbp) measured in the doctor's office and on the parametrs of bpm (daily sbp and dbp, daytime and nighttime sbp and dbp, sbp and dbp variability, the rate of morning rise in sbp and dbp). we revealed a favorable effect of the medication on vascular wall elasticity, valid reduction of cholesterol, low-density lipoprotein cholesterol, triglycerides, dc, homocysteine and uric acid increase in sod in group . the proved antihypertensive effect of the candesartan therapy against a background of normalization of vascular wall elasticity, plasma lipids and processes of lipid peroxidation, in the presence of differently directed correlations between clinical and biochemical characteristics, shows that candesartan has pathogenetic mechanisms of correcting ah in females with ah and ao during menopause. background: high intensity interval training (hiit) may improve insulin action in skeletal muscle, but this has never been shown. objective: to study the effect of hiit on insulin mediated glucose uptake rate in skeletal muscle. methods: four healthy sedentary males [age ae years (mean ae se), bmi . ae . kg/m ] were included. a total of eight one-legged training sessions were performed on an ergometer bicycle as min high intensity exercise (workload > % of one-legged vo -peak, and heart rate > % of maximal heart rate) with min recovery between each interval. lean leg mass before and after the training period was assessed using dual-energy x-ray absorptiometry. forty hours after the last training session, a two-step isoglycemic, hyperinsulinemic clamp was performed in combination with arteriofemoral venous catheterization. blood flow was measured with doppler ultrasonography. data were expressed per kg lean leg mass, and differences were tested by t-test. results: insulin stimulated glucose clearance rates were significantly higher in trained compared with untrained legs in both steps of the clamp (figure). the lean mass of the trained legs did not significantly differ from the untrained legs (p = . ). conclusion: hiit increases insulin stimulated glucose uptake in skeletal muscle in the leg after a very short training period. it is a time-effective training modality which may be attractive in the treatment of insulin resistance and type diabetes. (htgpos) and that this htgpos is related with the degree of insulin resistance. our aim was to characterize the adipose tissue of morbidly obese patients with mild or severe htgpos after a fat overload though the expression of a battery of genes involved in lipid metabolism. methods: we studied morbidly obese patients who had mild or severe htgpos after fat overload (patent p ). measurements of anthropometric and biochemical variables and oxidative stress biomarkers were done. samples of visceral adipose tissue were obtained during bariatric surgery in the morbidly obese patients. the rna isolation from adipose tissues was done using rneasy lipid tissue mini kit and the gene mrna expression levels were assessed by real-time pcr using an abi prism sequence detection system. results: no significant differences were observed in biochemical variables except in triglyceride levels between the two groups of morbidly obese patients with postprandial mild or severe htgpos. the morbidity obese patients with severe htgpos had a higher oxidative stress levels. genes involved in the management of triglycerides or lipid metabolism were up-regulated in morbidly obese patients with severe htgpos. conclusion: morbidly obese patients with severe htgpos had a more active adipose tissue regarding the expression of genes involved in lipid metabolisms, these data could indicate a greater flow of lipids and a greater insulin resistance in these patients. patients and methods: three hundred and nine workers ( m/ f; aged ae ; bmi . ae . kg/m ), without previous cardiovascular events, were enrolled. all subjects were evaluated for biochemical analytes (fibrinogen, c-reactive protein, uric acid, creatinine, triglycerides, t-cholesterol, hdl, ldl, homocysteine, glucose, insulin, hba c, (oh) d). all parameters were routinely assayed in corelab. these parameters together with homa-ir, systolic and diastolic blood pressure, bmi, age, percent of fat and waist circumference were processed by neural networks (autocm). the autocm matrix of connections preserves non linear associations among variables, while at the same time capturing elusive connection schemes among clusters that are often overlooked by traditional cluster analyses. results: with an appropriate pre-processing able to handle each variable according to its high and low values, auto-cm showed a clear association between (oh) d and metabolic status with graph links suggesting a protective role of high (oh) d against increase in bmi, waist circumference and abdominal fat. these associations were not clearly visible with traditional data mining tool. the neural networks map identifies the key role of vitamin d respect to all metabolic parameters considered in our study in the development of prediabetes drawing a physiopathologic road map for obesity and type diabetes. patients and methods: the study included type diabetic patients and healthy volunteer of the same age and sex. blood sample was taken for assessment of omentin and oxldl by elisa technique. also blood sample were taken for analysis of glycosylated hemoglobin, lipid profile and urine sample was taken for assessment of albumin/creatinine ratio. twenty-four hour holter was also done. the study included patients with type diabetes, their mean age were . ae . years ( . - . years), and mean duration of diabetes were . ae . years ( . - . years). omentin was significantly lower, while oxldl was significantly higher than controls. omentin had a significant negative correlation with oxldl and albumin/creatinine ratio and h holter (minimal hr, rms) and positive correlation with vldl. conclusion: a significant reduction of omentin and elevation of oxldl imply that they influence glucose metabolism in type diabetes. omentin had a significant relation to h holter may reflect its role in cardiac affection. while, albumin/creatinine ratio had a significant negative correlation with omentin and positive correlation with oxldl reflect their role in renal affection. patients and methods: the study included type diabetic patients and healthy volunteer of the same age and sex. blood sample was taken for assessment of chemerin, vaspin, adma and oxldl by elisa technique. also blood sample were taken for analysis of glycosylated hemoglobin, lipid profile and urine sample was taken for assessment of albumin/creatinine ratio. twenty-four hour holter was also done. the study included patients with type diabetes, their mean age were . ae . years ( . - . years), and mean duration of diabetes were . ae . years ( . - . years). chemerin, vaspin and oxldl were significantly higher, while adma was significantly lower than controls. chemerin had a significant positive correlation with vaspin, adma and oxldl. vaspin had a significant positive correlation with waist/height ratio, sdann, sdrr and sddrr. albumin/creatinine ratio had a significant positive correlation with chemerin, adma and oxldl. conclusion: a significant reduction of adma and elevation of chemerin, vaspin and oxldl imply that they influence glucose metabolism in type diabetes. vaspin had a significant relation to h holter may reflect its role in cardiac affection. while, albumin/ creatinine ratio had a significant positive correlation with chemerin, adma and oxldl reflect their role in renal affection. patients and methods: the study included type diabetic patients and healthy volunteer of the same age and sex. blood sample was taken for assessment of apelin, nitrous oxide and preptin by elisa technique. also blood sample were taken for analysis of glycosylated hemoglobin, lipid profile and albumin/creatinine ratio in urine. m mode echocardiography was also done. results: the study included patients with type diabetes, their mean age were . ae . years ( . - . years), and mean duration of diabetes were . ae . years ( . - . years). nitrous oxide was significantly lower, while apelin, preptin and albumin/creatinine ratio were significantly higher than controls. nitrous oxide had a significant positive correlation with lvedd, lvesd, pwt and lv mass and negative correlation with preptin and albumin/creatinine ratio. conclusion: a significant reduction of nitrous oxide and elevation of apelin and preptin and their relation to echocardiographic data imply that early assessment of these markers may unmask the initial endothelial dysfunction in type diabetic patients before overt microalbumin and renal impairment supervenes. obesity co-morbidities may appear already early in life in high-risk individuals. today we have no means to identify which obese children who are at highest risk. consequently, we have implemented a study with the objective to identify factors in obese children that could indicate early development of related co-morbidities. in this abstract we have concidered fasting glucose, h ogtt, and degree of obesity as predictors. severely obese children and adolescents treated for obesity between and (n = ), but not undergone bariatric surgery, are included. currently, follow-up measurements have been conducted in subjects. study participants undergo extensive examinations during days including e.g. cardio respiratory fitness, body composition, both oral and intravenous (ivfsgtt) glucose tolerance tests. average age of the first subjects is . years ( . - . ). follow-up time varies from . to . with an average of . years. bmissds at baseline . ( . - . ) correlates with bmi at follow-up (y = . x + . , r = . ). no other correlations with degree of obesity at baseline could be found. fasting glucose at baseline correlates with crp . years later. however, fasting glucose was not correlated with h ogtt, insulin sensitivity, diabetes, or prediabetes at follow-up. no correlations between h ogtt value at baseline and later co-morbidity was found. in the first studied subjects all, but one, of the severely obese children remained obese in early adulthood. higher level of fasting glucose at baseline predicted higher crp at follow-up. analyses from more collected data will be presented. background: obesity acts as an independent cardiovascular risk factor by mechanisms that are not fully understood. elevated levels of the pro-inflammatory cytokines interleukin(il)- , il- and plasminogen activator inhibitor (pai)- are found in obese patients. recent studies suggest that inflammation could be an adaptive response to hypoxia within the expanding adipose tissue mass. in this study we investigated the impact of hypoxia on pai- , il- and il- regulation in human adipose tissue ex vivo and in vitro. methods: primary human preadipocytes and adipocytes were prepared from subcutaneous and visceral adipose tissue. explants, preadipocytes and adipocytes were cultured under hypoxic conditions. pai- , il- and il- antigen were quantified by elisas, mrna levels were determined by realtimepcr. results: pai- , il- and il- secretion was significantly increased under hypoxic conditions in subcutaneous and visceral adipose tissue explants. hypoxia significantly upregulated il- production in preadipocytes and adipocytes up to -fold and -fold. il- and pai- were significantly increased by hypoxia in preadipocytes and adipocytes up to -fold and -fold (il- ) and . -fold and . -fold (pai- ), respectively. these results were confirmed on the level of mrna expression. conclusion: our data show that hypoxia increases il- , il- and pai- production in adipose tissue explants and in cultured human preadipocytes and adipocytes. we therefore hypothesize that hypoxia promotes the pro-inflammatory state seen in obese patients and thus could contribute to the elevated risk for cardiovascular diseases. this study sought to characterize the antioxidant properties and interaction of phenolic (free and bound) extracts from clerodendrum volubile (a leafy vegetable commonly grown and consumed in south eastern part of nigeria), with key enzymes relevant to non-insulin dependent diabetes mellitus (a-amylase and a-glucosidase) in vitro. the free phenolics of clerodendrum volubile were extracted with % acetone, while the bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate; and their interaction with the enzymes were assessed. the phenolic extracts inhibited a-amylase, aglucosidase and fe + -induced lipid peroxidation in pancreas (in vitro) in a dose-dependent manner. however, bound phenolics had significantly higher (p < . ) a-glucosidase inhibitory activities, than free phenolics while there was no significant difference (p > . ) in their a-amylase inhibitory activities. the stronger inhibition of a-glucosidase when compared to a-amylase in both extracts is of pharmacological relevance. the stronger action of the bound phenolic extract on a-glucosidase may explain the possible bioactivity of the phenolics at the brush border end. the phenolic profile in both extracts revealed the presence of phenolic acids and flavonoids. moreover, the inhibitory properties of phenolic rich extracts from clerodendrum volubile on a-amylase, a-glucosidase and fe + -induced lipid peroxidation in pancreas could be attributed to the antioxidant properties of the extracts. from the study, clerodendrum volubile could serve as functional foods and nutraceuticals for early intervention and management of non-insulin dependent diabetes mellitus. department of kinesiology and nutrition, university of illinois at chicago, chicago, il, usa background: alternate day fasting (adf), consisting of a feed day ( -h ad libitum food intake) alternated with a fast day ( % energy restriction), is effective in reducing body weight and modulating adipose tissue physiology. however, the ability of adf in combination with endurance exercise to improve the above variables has never been tested. objective: accordingly, this study examined whether the combination of adf plus exercise produces superior changes in body weight and plasma adipokine levels, when compared to each treatment alone. methods: obese subjects (n = ) were randomized to one of four groups for weeks: . combination (adf + endurance exercise), . adf, . exercise, or . control. results: body weight was reduced (p < . ) by ae , ae , and ae kg, and fat mass decreased (p < . ) by ae , ae and ae kg in the combination, adf and exercise group, respectively. fat free mass was retained in all groups. adiponectin and resistin values did not change in any group post-treatment. leptin levels significantly decreased (p < . ) by ae , ae and ae ng/ ml in the combination, adf, and exercise group, respectively. conclusion: these findings suggest that the combination of adf plus exercise produces superior changes in body weight, body composition and leptin levels, when compared to each intervention alone. the plasma total cholesterol and triglycerides concentration were higher than other groups. adipokines results were that resistin, adiponectin, leptin, and tnf-a were significantly lower than [hf], [br] and [hc] . so it had a effect on anti-obesity. these results showed that functional rice especially giant embryonic components will probably be useful in the management of high fat diet-induced chronic disease. m.g. watve , m.s. diwekar , p. patil biology, indian institute of science eduction and research, physiology, bharati vidyapeeth medical college, pune, india a crucial link in the classical thinking of type diabetes (t d) is that insulin resistance (ir) is primary and hyperinsulinemia develops to compensate. high levels of insulin are associated with an insulin resistant state. there have been alternative suggestions that insulin overproduction is primary and ir develops to compensate it. it is also likely that both are secondary effects of an unknown primary cause. we critically examine the alternative possibilities in the light of theory and evidence. temporally hypoglycemia and/or hyperinsulinemia precede insulin resistance in human and animal iugr models. various gene knockouts show that primary muscle and adipose insulin resistance does not lead to hi. in insulinomas, where hyperinsulinemia is primary, insulin resistance develops almost invariably and removal of such tumors increases insulin sensitivity. if ir sets in first, pancreas must sense the ir and increase the insulin production accordingly. if raised blood glucose mediates the response, we expect a positive correlation between fasting glucose and fasting insulin in prediabetic individuals. however, such a correlation is not seen in a large set of data on normoglycemics. no other mechanisms have been postulated that can measure the level of ir and in turn regulate the insulin secretion by beta cells. on the other hand many pathways exist that can induce ir when beta cells overproduce insulin. overall there is substantially more evidence for the hyperinsulinemia-first hypothesis. this can potentially undermine our current understanding of t d and the entire chain of processes leading to t d needs to be re-examined. non-alcoholic fatty liver disease (nafld) is emerging as the most common liver disease in industrialized countries. the discovery of food components that would ameliorate nafld is therefore of interest. betulinic acid (ba) is a pentacyclic triterpenoid showing many pharmacological activities, but effect of ba on fatty liver is largely unknown. to explore the anti-fatty liver activity and mechanism of ba, insulin resistant hepg cells, primary rat hepatocytes and liver tissue of icr mice fed on hfd were utilized. oil red o staining revealed that ba significantly suppressed the excessive triglyceride accumulation in hepg cells and liver of mice fed on hfd. ca + -calmodulin dependent protein kinase kinase (camkk) and amp-activated protein kinase (ampk) were both activated by ba treatment. in contrast, protein expression of sterol regulatory element-binding protein (srebp ), mammalian target of rapamycin (mtor) and s kinase (s k) were all suppressed when hepatocytes were treated with ba for up to h period. ba activated ampk by phosphorylation, suppressed srebp mrna expression and nuclear translocation and repressed srebp target gene expression in hepg cells and primary hepatocytes, leading to reduced lipogenesis and lipid accumulation. these effects were completely abolished in the presence of sto- (a camkk inhibitor) or compound c (an ampk inhibitor), indicating that bainduced anti-hepatic steatosis was mediated through modulation of camkk-ampk-srebp signaling pathway. taken together, our results suggest that ba can effectively ameliorate intracellular lipid accumulation in liver cells, and thus it may be a potential therapeutic agent for treating fatty liver disease. blood glucose concentration, insulin level, glucokinase, g pase and pepck were significantly decrease relative to the [hf] . in addition, antioxidantresults were that cat, sod and gpx were higher than [hf] . effect of rice supplementation type of giant embryonic on erythrocyte tbars and plasma tbars showed significantly decrease than other groups. these experiments suggest that components of giant embryonic help to lower the level of and blood glucose which reduces the risk of heart disease and diabetes. method: a g o-gtt was performed in normal-weight (n) healthy females, females with overweight and females with obesity (grades - ), with measurements of glucose and insulin. homa-insulin resistance (ir) and belfiore-insulin sensitivity (is) were caldulcated. the th percentile in the n group was used as cut-off. results: ir was present in . % of women with normal weight and in . % of women with overweight/obesity. . %, . % and . % of women have ir in the obesity grade , and , respectively. further risk factors for ir are age, hip-waist ratio, triglycerides, hdl, uric acid, pai- and fibrinogen (p < . ). hba c is irrelevant for the detection of ir. hormonal imbalances (hyperandrogenemia, igf deficiency, hypothyroidism, elevated estradiol) play a major role in obese women. postmenopausal women receiving hormone replacement therapy (hrt) develop hyperglycemia, as expected by age, but not ir. hrt improves is. discussion: ir is the common pathogenetic factor for risk components summarized as "metabolic syndrome": dyslipidemia, hypertension, hyperandrogenism and obesity. the vicious circle is intensified with the degree of ir. during the to -year interval between the onset of ir and the manifestation of dm, significant micro-and macroangiopathies can develop. early detection of ir is therefore crucial for the prevention of dm and cvd. the costs involved for diagnosis are minimal ( - €) compared to the cost of treatment for dm and cvd. the effect of dietary feeding of "superjami" on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. the mice were randomly divided and given experimental diets for weeks: normal control (nc group), high fat (hf group), and high fat supplemented with heukjinju (hf + hj group), suwon (hf + sw group) and superjami (hf + sj group). at the end of the experimental period, the hf group exhibited markedly higher blood glucose level. however, diet supplementation of superjami was found to counteract the high fatinduced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. these findings illustrate that superjami was similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat diet-induced hyperglycemia and oxidative stress. objective: to evaluate the effectiveness of two types of intervention: personal and group therapy in preventing or delaying diabetes. methods: two hundred and twenty-two pre diabetes adults were assigned to both interventions, which included physicians, dietitians, social workers and physical activity consultants, to modify patients' lifestyle and reduce weight. glucose, total cholesterol, ldl, hdl; tryglesirides and bmi were measured before (t ), immediately after (t ) and post months (t ) of the intervention. mix linear; logistic regression and cox models were employed. results: mean age was . and . (p = . ) for the personal and group therapy, respectively. no significant differences in time trends for all the clinical measurements between the groups were observed. however, (i) reduction (À . p < . ) in glucose for the personal therapy group between t and t ; (ii) reduction in total cholesterol (À . p = . ; À . p < . ) in personal and group therapy, respectively, between t and t ; (iii) significant hdl increase in both groups between t , t and t ; and (iv) significant decline in ldl, triglycerides and bmi between t t and t . . % and . % of the group and personal therapy, respectively (p = . ), developed type diabetes during the study period. no differences to time to onset of the disease between the two groups. conclusion: for patients with pre diabetes, both types of intervention were effective in delaying and preventing the disease. group therapy is recommended since it requires fewer resources and can be implemented for the benefit larger population. methods: the present population-based case-control study was performed in shiraz, southern iran, over a -month period from december to , on a randomly selected study population group consisting of inhabitants of the metropolis of shiraz in southern iran. all the patients underwent anthropometric and blood pressure measurements as well as thorough medical history and physical examinations. laboratory parameters including fasting blood glucose, lipid profiles, liver enzymes and ferritin, in addition to liver ultrasonography and cimt, were performed for all subjects. the cutoff value for the cimt was set at . mm and the measured values were correlated with other risk factors. we evaluated patients with nafld and the same number of controls. subjects with nafld had a significantly higher prevalence of increased cimt (or: . , p < . ). in patients with nafld the age of years represented an appropriate cut-off value for predicting increased cimt. a systolic blood pressure (sbp) of mmhg and a diastolic blood pressure (dbp) of mmhg were shown to be appropriate cut-off values for predicting increased cimt. conclusion: cardiovascular risk factors such as increased intimamedia thickness (imt) occur more frequently among nafld patients when compared to healthy individuals. we recommend a careful evaluation of not only the liver, but also of the cardiovascular system in these patients, in order to prevent later morbidity related to atherosclerosis. mitochondrial capacity of oxidizing fatty acids and increased mitochondrial ros production. the peroxisomal β-oxidation, which starts the oxidation of the long-chain fatty acid and contributes with approximately % of all oxygen peroxide produced in the cell, was increased in ovx mice. these effects could lead to oxidative damage, a condition that was, in fact, evidenced by the reduced levels of reduced glutathione and elevated levels of tbars found in livers of ovx mice. the decreased mitochondrial capacity of oxidizing fatty acids could contribute, at least in part to development of hs in ovx mice. besides, the higher mitochondrial and peroxisomal ros generation resulted in oxidative damage in livers from ovx mice. background: elevations in high-sensitivity c-reactive protein (hs-crp) are associated with an increased risk of insulin resistance (ir). investigation of relationship between hs-crp, parameters of glucose metabolism and leptin in patients with t dm and igt could be help to assess the role of hs-crp in development of ir. aim: of the study was investigation of relationship between hs-crp and hepatic glucose production (hgp), leptin and hba c in women with t dm and igt. materials and methods: forty-eight women with igm ( newly diagnosed t d and igt were observed). hs-crp and leptin were assessed in fasting states. intravenous glucose tolerance test was performed ( . г glucose on kg of body mass). mathematical analysis of results with definition of hgp (the h-index, mmol/l) was done with the special program (accessible in internet: www.diabet.ru/ivgtt). results: bmi was significantly correlated with hs-crp, r = . , p < . and the level of hs-crp in women with bmi > kg/m was almost four times greater compare to hs-crp in women with bmi > kg/m [ . ( . - . ) and . ( . - . ) accordingly, (p < . )]. between hs-crp and hgp and between hs-crp and leptin direct correlation (r = . , p < . ) and (r = . , p < . , accordingly) was revealed. correlation between hs-crp and hba c wasn't found. conclusions: association between hs-crp and leptin level, hs-crp and hgp could be demonstrate the role of hs-crp in development of insulin resistance. institute for sport and physical activity research (ispar), university of bedfordshire, bedford, uk objective: hypertriglyceridemic waist (hw) and waist-to-height ratio (whtr) are simple clinical tools that identify adults at risk of cardiometabolic disorders and cardiovascular disease. whether this applies in youth is under-researched and this study therefore investigated whether the hw phenotype and whtr are associated with cardiometabolic disorders in children and adolescents. methodology: this was a cross-sectional design study. anthropometry, biochemical variables, and cardiorespiratory fitness were assessed in participants ( girls) aged - years from bedfordshire, united kingdom. the hw phenotype was defined as a waist circumference ! th percentile for age and sex, and triglyceride concentrations ! . mmol/l, and a high whtr defined as > . . ancova and logistic regression were used in the analysis. results: in participants with the hw phenotype, clustered risk score was lower (p < . ), the odds of having high cardiorespiratory fitness (ml/kg/min) lower ( . ; % ci . , . ), and the odds of having low hdl-cholesterol ( . ; . , . ), impaired fasting glucose ( . ; . , . ), and ! ( . ; . , . ) and ! risk factors ( . ; . , . ) higher than those without the phenotype. those with a high whtr had lower clustered risk (p < . ), higher odds of having low hdl-cholesterol ( . ; . , . ), high diastolic blood pressure ( . ; . , . ) , and ! risk factors ( . ; . , . ) than those with normal whtr. conclusion: the hw phenotype may be a better simple marker than whtr for identifying children and adolescents at risk for cardiometabolic disorders. treatment with ace inhibitors (acei) and at receptor blockers (arbs) has been shown to reduce the number of new-onset dm , improve insulin sensitivity and reduce adipocyte size , . we investigated additional metabolic effect of renin-angiotensin system (ras) blockade with arb in comparison with acei. specifically we studied the effect of candesartan cilexetil therapy on glucose metabolism and parameters of subcutaneous adipose tissue (sat) in hypertensive subjects. antihypertensive treatment with acei was replaced by candesartan for months in subjects with essential hypertension. experimental procedures involved measurements of anthropometric data, blood pressure, oral glucose tolerance test, ras components and adipokines gene expression in sat obtained by biopsy. intersticial fluid from sat was collected by using microdialysis. six months after replacement acei by candesartan, the systolic blood pressure decreased by . ae . mmhg (p < . ), diastolic blood pressure decreased by . ae . mmhg (p < . ) and fasting plasma glucose decreased by . ae . mmol/l (p < . ). insulin sensitivity index (matsuda) tended to increase (p = . ). among the adipokine and ras genes studied in sat only pparc expression tended to increase (p = . ) after candesartan treatment. as expected, candesartan had blood pressure lowering effects comparable to those of acei. seeing that candesartan reduced fasting glycemia and strongly tended to increase pparc expression in sat, we speculate that arbs treatment might have additional positive effect on glucose metabolism compared to acei. the study is continuing and samples of serum and microdialysate are currently under analysis of ras peptide content. purpose: diastolic dysfunction in the metabolic syndrome/type diabetes (d) is an epidemic without evidence-based treatment strategies. studies on dietary interventions are scarce. we tested the hypothesis, that a low-carbohydrate diet (lc) improves cardiac function in overweight-obese d more than the traditionally recommended low-fat diet (lf). methods: two groups of d without cardiac disease (bmi ae kg/m ) were studied in a parallel and partial cross-over design during a -week rehabilitation program with either lc or lf. the group on lf (carbohydrate %, fat %, protein %) had subsequent weeks on lc ( %, %, %, respectively). cardiac function was assessed as myocardial velocity during systole and diastole (e′) and metabolic control before and h after (pp) a standardized breakfast ( kcal). both groups had supervised aerobic training h a day. results: in the parallel groups, both diets induced similar and significant reductions of weight, hba c and cholesterol. lc considerably improved insulin resistance, triglycerides, systolic and diastolic blood pressure and e′ ( . ae . - . ae . cm/s, p = . ), but lf did not whereas all these variables improved significantly after subsequent lc (e′ from . ae . to . ae . cm/s, p = . ). intact proinsulin was unchanged with lf but decreased with subsequent lc fasting and pp (p = . and . ). conclusions: these data indicate, that a lc but not lf nutrition modulates diastolic dysfunction in overweight diabetics, improves insulin resistance and may prevent or delay the onset of diabetic cardiomyopathy and the metabolic syndrome. methods: we studied adolescents, males (n = ) and females (n = ), who were collected waist circumference, office bp, serum glucose and lipids. they underwent a -h abp monitoring (abpm) to record -hs, awake and sleep bp, and the bpv was calculated as the standard deviation bp. the ms was defined according to the national cholesterol education program, adult treatment panel iii modified for adolescents. statistical analysis: the variance ratio test (f-test) was applied to compare the bpv between adolescents with ms and those without ms. results: the ms prevalence was . % (n = ) in all, . % (n = ) in males and . % (n = ) in females (p < . ). the abp values (systolic/diastolic) were the following: / , / and / mmhg in adolescents with ms; and / , / and / mmhg in adolescents without ms, for -hs, awake and sleep periods, respectively. the highest statistically significant values in systolic and diastolic abp during -hs and awake and systolic abp in sleep were showed by ms group. likewise, adolescents with ms showed significant higher -hs systolic bpv than those without ms ( . vs. . mmhg, p < . ). the ms has important effects on the abp values in adolescents. also, systolic bp variability during -hs is associated with ms. these findings suggest that ambulatory blood pressure monitoring is important in adolescents with ms to detect subjects in cardiovascular risk. montfort hospital research institute, university of ottawa, ottawa, on, canada organochlorine compounds (oc), are chemicals that were mostly used historically as pesticides, solvents, flame retardants, and other applications. oc have been recognized to be of environmental and potential toxicologic concern. due to their persistence and lipophilicity, these compounds will remain present in the environment for decades and accumulate in living organisms. the presence of oc is a major concern since they could act as endocrine disruptors and have recently been associated with the development of hepatic steatosis and lipotoxicity. the objective of this project is to define intra-hepatic molecular mechanisms implicated in the development of hepatic steatosis and lipotoxicity in oc exposed hepatocytes and rats. results: lipid quantification was assessed in human hepatocytes using steatosis colorimetric assay (cayman chemical company). lipid accumulation was higher in hepatocytes exposed to pcb [ . lmol/l] for h compared to chloroquine ( %), a potential lipid droplet infiltration inducer, as well as our control group treated with dmso ( %). conclusion: understanding the emerging role of oc in the physiology of hepatic steatosis and lipotoxicity is of great importance as it is becoming clear that chronic lipotoxicity is strongly related to the suppression of insulin receptor signaling in the liver and activation of the apoptotic pathway. these results only represent the necessary first step on oc and their impact on the liver metabolic activity. experiments in oc-contaminated rats are presently undertaken, as well as protein quantification involved in intra-hepatic mechanisms in cells. nutrition, nutrition research institute, the university of north carolina at chapel hill, kannapolis, nc, usa insulin a precursor of t dm, various cardiocerebrovascular disorders, non-alcoholic fatty liver, alzheimer's disease, and many other major health problems associated with excess calories. to study the mechanism of insulin resistance, we investigated the role of insulin and each category of macronutrients (glucose, fat, and amino acids) in the development of insulin resistance. our results show that glucose (hyperglycemia) does not cause insulin resistance in the absence of insulin in cultured cells or animals. dietary carbohydrate is not necessary for high fat diet (hfd) induction of insulin resistance but a small amount of it can promote insulin resistance in the maximal level in animals on hfd. our results also show that fat is necessary for the development of insulin resistance although fat can't induce insulin resistance in the absence of insulin. supplementation of amino acids such as leucine does not necessary cause insulin resistance in animals on hfd. finally, our results show that insulin can cause insulin resistance through (i) accumulation of long-chain acyl coas and cholesterol in mitochondria, (ii) inhibition of production of new mitochondria; and (iii) turnover of aged/damaged mitochondria. in summary, our results show that insulin and each category of macronutrients are necessary for the development of persistent insulin resistance. wellness institute, cleveland clinic, cleveland, oh, usa background: lifestyle factors are key in the development and progression of chronic disease. here we report outcomes for prediabetic participants in the lifestyle â program, a -month intervention for patients with chronic diseases that integrates education in cooking, nutrition, exercise, and stress management. methods: pre-post changes in biometric, laboratory, and psychosocial variables were evaluated by paired student's t-test or wilcoxon test. results: of participants who met ada criteria for prediabetes (n = ), most were female ( %) and obese ( %) and had hyperlipidemia ( %) or hypertension ( %). one fifth ( %) had depression. average age was ae years. at month , biometric, laboratory, and psychosocial data were available for ( %), ( %) and ( %) participants, respectively. average bmi decreased by % ( . ae . - . ae . ) and there were decreases in waist circumference, blood pressure, resting heart rate, fasting glucose, and hba c (p < . for all). insulin decreased from . ae . - . ae . μu/ml (À . %; p < . ). more diabetic medications were stopped or reduced in dose than were started or increased in dose (ratio . : ). average depression (ces-d ) and perceived stress (pss- ) scores decreased by % and % respectively (p < . for both). physical, mental, and perceived health (measured by veterans rand item health survey) improved from % to % (p < . ). conclusion: participation in a comprehensive lifestyle modification program of adults with prediabetes results in significant and clinically meaningful improvements in biometric, laboratory, and psychosocial outcomes. diabetes is frequently associated with both extracellular and intracellular magnesium (mg) depletion. epidemiologic studies found high prevalence of hypomagnesaemia in subjects with type diabetes, especially with poorly controlled glycemic control. erythrocyte and serum magnesium levels were measured in healthy control subjects, non-diabetic normal glucose tolerant offspring of type diabetic subjects and non-diabetic impaired glucose tolerant offspring of type diabetic subjects in addition to routine laboratory investigations, hba c, lipid profile, fasting insulin by elisa and homa-ir. our study showed that fasting, h postprandial plasma glucose, serum insulin level, hba c, homa-ir index, serum ldl-c, serum triglycerides, serum cholesterol and serum malondialdehyde levels were higher and serum hdl-c and both serum and erythrocyte magnesium levels were lower in impaired glucose tolerant offspring of type diabetes as compared to each of normal glucose tolerant group and control group, while there was no significant difference in those parameters between normal glucose tolerant and control groups. we can conclude that the magnesium depletion and the increase in malondialdehyde level in non diabetic impaired glucose tolerant offspring of type dm were associated with increasing severity of insulin resistance and dyslipidemia and, this may increase the risk of development of type diabetes complications in there offspring. possily use of mg suplemenaion in those subject may delay and prevent the development of type diabetes. obstetrics and gynaecologist, catholic university of sacred heart, rome, italy background and aims: gdm, overweight and gestational weight gain (gwg) are important determinants for an adverse pregnancy outcome and particularly for having large for gestational age (lga) newborn. the aim of this study was to evaluate the pregnancy outcome among women affected by a gdm, belonging four different classes of pre-pregnant bmi and to investigate the specific role of the anthropometric parameters and therapeutic regimen on the foetal growth. material and methods: this was a prospective study including pregnancies affected by gdm. only women with a mean pre-prandial glucose level < mg/dl and h post-prandial values < mg/dl were enrolled. we considered other variables such as gwg, excessive gwg (egwg), therapeutic regimen used and maternal age to investigate their role in foetal growth. results: at the linear univariate analysis, a dependence of neonatal birth weight from pre-pregnant bmi class, egwg, gwg and gestational week at delivery was found (p < . ). the dependence from the pre-pregnant bmi (p = . ) and the egwg (p = . ) was confirmed even when the percentile was considered. at the multivariate analysis the birth percentile resulted associated both with the prepregnant bmi (p < . ) and the gwg (p = . ). conclusions: pre-gestational bmi, gwg and egwg are important parameters involved in fetal growth. their control during pregnancy could be an important way to improve pregnancy outcome even in women with gdm. obstetrics and gynaecologist, internal medicine, catholic university of sacred heart, rome, italy background and aim: continuous subcutaneous insulin infusion (csii) may be an alternative treatment to multiple daily injections (mdi) in pregnant subjects with type diabetes(¹). the aim of this study was to compare metabolic control and obstetric outcome of these pregnancies treated with csii vs. pregnancies treated with different type of insulin analogs administrated by mdi. material and methods: we studied pregnancies in women, three twin pregnancies, affected by type diabetes. thirty-four pregnancies treated with csii and treated with mdi treatment were evaluated. in the group of women treated with mdi women used human analogs, used insulin aspart and used insulin lispro. metabolic control and obstetric outcome were compared between the groups. statistically significant differences were found in metabolic control in term of hba c mean level for each trimester of pregnancy. conclusion: no clear advantage of csii vs. mdi treatment is shown in our study for pregnancies complicated by type diabetes in term of metabolic control or obstetric outcome(²). however, it might be that some selected patients with unstable metabolic control or high hba c levels, who become pregnant with a better metabolic profile after csii treatment, may have a better pregnancy outcome. poblations and methods: a cross-sectional study was performed on children and adolescents ( female and male) between and years old, without cardiovascular, metabolics, oncology and immunology diseases. were excluded all subjects who took drugs with effects on glucose, insulin, lipids or weight. each subject was determined: weight, height, bmi, neck, waist, hip circumferences, adiposity, blood pressure and glucose, insulin, cholesterol, tryglicerides, c-ldl, c-hdl. was performed oral glucose tolerance test to glucose and insulin postprandial. was estimated insulin secretion and insulin sensitivity. conclusi on: neck circumference is a potential marker for to identify children and adolescents with metabolic and cardiovascular risk factors. aim: to assess the efficacy of a lifestyle modification in preventing diabetes mellitus type (dm ) among subjects with risk factors of dm including impaired glucose tolerance and impaired fasting glucose (igt/ifg), obese adults and first-degree relatives of patients with diabetes. materials and methods: the study included patients ( m, f) - years old at risk factors of dm . all patients received recommendation on a balanced diet and physical activity. we measured fasting plasma glucose (fpg), -h plasma glucose concentrations. fasting serum insulin (fi) levels were detected by sensitive elisa. index homa-r were used as the index of insulin resistance. results: in weeks our study patients carried out this recommendations (research group) and patients did not it (control group). patients of the research group demonstrated mean reduction of weight (À . kg), bmi (À . kg/m ) and whr (À . ) (p < . ) and persons of the control group had significant increase these parameters (p < . ). among subjects with igt, glucose levels normalized in % of patients from the research group and . % in control group (p < . ). fi and homa-r in research group decreased from . ae . to . ae . lu/ml and from . ae . to . ae . accordingly (p < . ). in control group the specified parameters had increased significantly (p < . ). the risk reduction of development dm among patients of the research group was . % comparer the control group. conclusion: thereby, lifestyle modifications are effective in preventing dm development in individuals at risk living in belarus. objectives: it is suggested that the kind and frequency of snacks as well as dairy consumption can influence body weight and composition. as the number of students are increasing rapidly in iran and regarding their unhealthy food habits, we decided to carry out this study. methods: one hundred and twelve female students who were selected from university dormitories inhabitants randomly, participated in this cross-sectional study. weight, height and waist circumference (wc) of the participants were measured. demographic and food frequency questionnaires were filled face to face. data were analyzed using spss # . the results showed that . % of participants were under weight, % normal and . % overweight. besides, . % and . % had normal and above normal wc respectively. sixty-one percent of female students had just one snack. fruits ( %) and confectionaries ( %) were the most popular snacks. mean ae sd of the dairy consumption was . ae . serving per day. there were no correlations between bmi and wc and snacking pattern or dairy intake. conclusion: it is assumed that as most of our subjects had normal weight and wc, we did not find any correlation between bmi and wc and snacking pattern or dairy intake. conducting similar studies, using both overweight and normal weight subjects is suggested. obstetrics and gynaecologist, catholic university of sacred heart, rome, italy background and aims: the management of pregnancies complicated by t dm has changed with the introduction of new short acting insulin analogs. the aim of this study was to have a comparison of obstetric outcome among the different insulin regimens. methods: one hundred and sixty singleton pregnancies were assessed. seventy-four women were treated with human analogs, with insulin aspart and with insulin lispro. results: no significative differences were found in term of incidence of pre-eclampsia, iugr, large for gestational age newborn, cesarian sections, preterm delivery, apgar score < , mean week at delivery, mean birth percentile. a significative difference was found in term of incidence of newborn infants with a birth weight ! g ( . % in the human analogs group, . % in the aspart group t and . % in the lispro group; p = . ); a trend (p = . ) was observed comparing the mean birth weight among the groups ( . ae . g in human analogs group, . ae . g in aspart group and . ae . g in lispro group). no significative differences were found in term of hba c mean levels for each trimester of pregnancy. conclusions: the use of insulin aspart is correlate with a lower incidence of fetal macrosomia and with a lower mean birth weight. in vitro observations highlighted that lispro and aspart have a similar affinity for insulin receptor; regarding the affinity for igf- receptor lispro is . fold more potent than human insulin in binding igf- receptor. further investigations are necessary to explain the correlation between insulin affinity for igf- receptor and fetal growth. methods: this study was performed on women diagnosed with gdm (gestational dm) - months after delivery. the jewish and bedouin women were divided into, intervention and control groups. the intervention group was instructed in healthy lifestyle habits every several months by a dietician and sports instructor. the control group was informed of the potential risks for diabetes following gdm and advised to improve lifestyle. all women had fasting insulin, glucose and lipid level tests - months post partum. height, weight, bmi, blood pressure, waist circumference were measured. food frequency and exercise questionnaires were filled. the same tests were repeated at and years follow up. results: the prevalence of gdm was . % in jewish and . % in bedouin women. lack of pregnancy care was greater among the bedouin. all the metabolic tests post gdm period improved in the intervention group in both ethnicities compared to control. there was a decrease in insulin, glucose, ldl, triglycerides and homa-ir (homeostasis model assessment) values and an increase in hdl. a significant decrease in carbohydrate consumption, calorie consumption, fat consumption and increase in protein consumption was observed and an increase in physical activity. the intervention program significantly improved the metabolic indices measured in both jewish and bedouin populations. the results underscore the need to provide lifestyle optimization guidance to women with gdm in order to reduce the risk of type diabetes. introduction: fatty liver is strongly associated with type diabetes. however, it is unclear whether hepatic triglyceride accumulation causes diabetes, or merely is a consequence of excess adipose tissue, that is related to insulin resistance. we aimed to investigate the association between hepatic triglyceride content (htgc) and insulin resistance, and whether this association could be explained by measures of adiposity. methods: in this cross-sectional analysis of the netherlands epidemiology of obesity (neo) study, fasting glucose and insulin concentrations were measured. abdominal fat depots were measured using mri, htgc using mrs. we performed linear regression analysis of htgc with the updated homeostasis model assessment (homa -ir), adjusting for age, sex, ethnicity, education, smoking, alcohol consumption, visceral adipose tissue (vat) and total body fat (tbf). results: after exclusion of participants with missing data (n = ) or known diabetes (n = ), alchohol consumption > glasses/day (n = ), participants were included with a median (iqr) age of ( . ) years, mean fasting glucose: . ae . mmol/l, % men. per sd htgc ( . %), the homa -ir increased with % ( % ci: %, %), this attenuated to % ( % ci: %, %) after adjustment for vat and to % ( % ci: %, %) after additional adjustment for tbf. per sd vat ( . dm ) the homa -ir increased with % ( % ci: %, %), this attenuated to % ( % ci: %, %) after adjustment for htgc and to % ( % ci: %, %) after additional adjustment for tbf. the association between hepatic fat and insulin resistance was for a large part explained by vat. vat may be most important in the etiology of insulin resistance. the aim was to carry out complex estimation of mutual relations between the proinflammatory condition and basic components of the metabolic syndrome (ms) in patients with ischemic heart disease hospitalized for coronary artery bypass grafting. forty-three patients were examined by standard methods and were divided into three groups depending on presence of separate ms components: st group with abdominal obesity (ao), arterial hypertension (ah), type ii diabetes, dyslipidemia; nd group with ao, ah, hyperglycemia; rd group with ao, ah, dyslipidemia. indicators of chronic subclinical inflammation have been revealed before operation in all groups of patients. the strongest ones have appeared in the nd group of patients. hyperuricemy was more frequently registered in patients of the rd group ( . %). the correlation analysis revealed authentic interrelations of uric acid level with lipid profile and inflammation markers. a strong inverse relation with triglycerides, a strong direct relation with low density lipoprotein cholesterol and inverse one with total amount of leukocytes were revealed in the st group. the strong direct relations with segmented neutrophils and the inverse ones with lymphocytes were registered in the nd and rd groups. the average direct correlation with crp was revealed in the rd group. activation of inflammatory process was noted in patients of all groups after operation, and it was already of acute nature in the rd group that allows attributing it to a risk group. the study of expressiveness of inflammatory reaction depending on presence of the ms components allows revealing risk groups among patients. introduction: the soft drink intake has increased worldwide and its high consumption is associated with the development of metabolic syndrome. objective: to estimate the association between the consumption of sugar-sweetened beverages (ssb) and the burden metabolic syndrome diseases (bmsd). a cross-sectional telephone survey was conducted with adults ( . % men and . % women, mean age . years) in the urban area of belo horizonte, brazil. data from the telephone-base brazilian surveillance system for chronic diseases was used (vigitel - / ). burden metabolic syndrome diseases were defined as the self-reported of at least two of the following factors: diabetes, dyslipidemia, hypertension and obesity. the intake of ! days/week soft drinks and artificial juices was assessed. sociodemographic, selfreported health status and lifestyle habits were also used. odds ratios (or) and % confidence intervals were estimated by multivariate logistic regression. results: in this sample, . % of participants consumed ! days/ week sugar-sweetened beverages (ssb). the prevalence of bmsd in the sample was . %. the prevalence of bmsd in people who consumed ssb ( ! days/week) was lower than people didn't consume the beverages (or: . ; % ci: . - . ) five or more days per week. the final model was also adjusted for physical activity, education, marital status, poor self-reported health and poor consumption of fruits and vegetables. obesity is an heterogeneous condition due to fat distribution and storage. the aim of our study was to compare the predicting role of homa index and of bmi on early vascular impairment in morbidly obese subjects (bmi . ae kg/m ) before and after sleeve gastrectomy (sg). glycemia, insulinemia, lipids, flow mediated dilatation (fmd), carotid intima media thickness (imt) and visceral fat area (vfa) by ultrasound were performed in all subjects. patients were divided on the basis of homa-ir median values: ! . group , < . group . group had significantly higher values of bmi (p < . ), waist circumference (p < . ), vfa (p < . ), triglycerides (p < . ), glycemia (p < . ), and lower hdl-c (p < . ) than group ; fmd was significantly lower (p < . ) and imt significantly higher (p < . ) than in the group . the same population divided on bmi median values did not show any difference in lipids, imt and fmd. at stepwise regression analysis vfa was the independent predictor of reduced fmd (β À . , p . ). homa-ir (beta . p < . ) was the independent predictor of imt (beta . , p = . ). in patients, re-evaluated months after sg, bmi, vfa and homa were significantly reduced (p < . ); fmd significantly increased only in the subgroup with homa-ir pre intervention ! . (p . ). bmi, index of overall adiposity, seems less useful in the prediction of early atherosclerosis in morbidly obese; homa-ir, strictly related to visceral fat, is expression of metabolic impairment thus able to predict early vascular damaging. methods: swiss albino mice were given a high fat diet containing lard (h) ( . % wt/wt), supplemented with as or f and in combination alongwith h (f + as + h) for weeks. the control mice (c) were fed with normal diet. after the treatment period the physical, physiological and cellular parameters were evaluated by body weight, liver weight, biochemical estimation, western blot, pcr or ihc. results: the h mice exhibited increased body and liver weight; treatment with f or as and (f + as + h) in the diet significantly counteracted the hfd induced body and liver weight gain, hyperlipidemia; hepatic lipid profile; level of ros; hyperglycemia; hyperinsulinemia; tnf-a, il- level; nuclear translocation of nf-jb; lipid peroxidation. activities of antioxidant enzymes (sod, cat, gsh, frap) were up regulated significantly in f or as and (f + as + h) mice. therefore simultaneous treatment with as or f and their combination protected against hfd induced weight gain and oxidative stress. conclusion: this novel approach of combinatorial preventive medicine is validated not only with the parameters of metabolic syndromes yet it is evidenced with oxidative stress and crucial molecular targets. this study illustrates for the first time that as and f has relatively similar hypolipidemic, antioxidative, anti inflammatory actions and the as + f combination along with hfd has shown prominent preventive effects as compared to other treated groups. s. sivapraksh , i. shabir , n. gupta , j. john , a. ammini aiims, department of endocrinology, aiims, new delhi, india background: insulin resistance/hyperinsulinemia is associated with a variety of reproductive endocrine dysfunction in girls. however, there is a scarcity data regarding hypothalamic pituitary testicular axis functioning among boys with hyper insulinemia. aim: aim of this study was to assess effect of hyper insulinemia on pubertal development in boys. subjects and methods: children of subjects with type diabetes mellitus (t dm) were invited to participate in this study. children and adolescent with any chronic medical condition were excluded. detailed medical history, physical examination including anthropometry, haemogram, liver, renal functions, oral glucose tolerance test (ogtt), insulin, lh, fsh, prolactin and testosterone were done for all subjects. results: seventy-four boys, - years of age participated in this study. results are given in table . thirty boys (all except were overweight) had gynaecomastia. objectives: to find out the prevalence and factors associated with dyslipidemia among adults aged years and above in a resettlement colony located in central delhi. a cross sectional study, that included a random sample of adults, was designed. a study tool based on the world health organisation (who) stepwise approach to surveillance of noncommunicable diseases and their risk factors (steps) questionnaire was used. fasting venous blood sample was collected. criteria based on the third report of the national cholesterol education program expert panel on detection, evaluation and treatment of high blood cholesterol in adults (ncep atp iii), were used to define the cut offs for dyslipidemia. data was analysed using the statistical package for social sciences (spss) version . results: out of a total of study subjects, % had raised cholesterol levels ( ! mg%). thirty-eight percent had raised low density lipoprotein (ldl) levels ( ! mg%), % had raised triglyceride levels (triglycerides ! mg%) and % had low high density lipoprotein (hdl) levels (< mg%). age, hypertension, alcohol consumption and abdominal obesity were found to be associated with increased odds of dyslipidaemia, using the logistic regression model. aim: in the present study we explored whether oral consumption of the probiotic lactobacillus casei shirota bacteria in form of the yakult probiotic drink has any effects on energy metabolism in patients with impaired metabolic functions. a cross-over-study with daily intake of one portion yakult light during weeks was carried out in patients with impaired glucose regulation or metabolic syndrome. fasting blood samples were collected, anthropometric parameters were measured and a frequently sampled oral glucose tolerance test was performed at time points (week , and ). effects on the human gut bacterial communities were studied via t-rflp fingerprinting of s rrna genes amplified from microbial dna preparations from fecal samples. our results reveal a significant increase of total cholesterol (mean increase: . mg/dl; p = . ), triglycerides (mean increase: . mg/dl; p = . ) and a significant decrease of hdl-cholesterol (mean decrease: . mg/dl; p = . ) after weeks of daily intake of yakult. no significant influence of yakult light consumption on indices of insulin sensitivity, hba c and ldl-cholesterol could be demonstrated. a small decrease of fasting glucose levels after yakult consumption was revealed (mean decrease: . mg/dl; p = . ). no consistent changes in the community profiles of the gut microbiota were observed following weeks of yakult light consumption. in mexico, breakfast is one of the most important meals during the day, but changes in food consumption habits, also known as nutritional transition have been associated with a poor food quality intake. scholars, during the recess use to buy some food in internal shops of schools and this food are not generally the healthiest. the aim of this study was to evaluate the quality of the food consumed during the recces by scholars in tepic nayarit, mexico. scholars ( , about - years) from different public schools were evaluated by means of food register questionnaires during days, there has determined the ingestion of nutrients and nourishment healthy index (ias) using the nutrition program dial. anthropometric data were measured for weight and height, and body mass index (bmi) was calculated. the bmi showed that . % of children have low weight for height, . % have normal weight and . % overweight/obesity. twenty percent of scholars declared that they did not take breakfast until the hour of recess. energy intake during recess was on average % of the daily requirement. the foods most frequently consumed were sweetened beverages ( ml) containing g of simple sugars, fried-wheat snacks ( g/ g fat), candies ( g/simple sugars) and some fruit such as mango, apple or watermelon ( g/portion) with chilli. these combinations of foods are risk factors to the development of diabetes in scholars were the prevalence of overweight/obesity is in high levels. introduction: incidence of type , and gestational diabetes mellitus (gdm) are increasing worldwide. given that women with previous gdm have a higher risk of diabetes development later in life compared to women with a physiological pregnancy, the aims of our study were (i) to ascertain a frequency of early postpartum conversion of gdm into permanent diabetes or persistent impaired glucose tolerance and (ii) to find an eventual significant predictive factors from those routinely measured during the gdm follow up. methods: we carried out a retrospective epidemiological analysis of anamnestic, anthropometric, biochemical and clinical data of female patients (n = ) from faculty hospital brno with gdm diagnosis during the - period that underwent repeated ogtt up to year after the delivery. results: any degree of impairment of glucose tolerance postpartum was detected in . % subjects, of those . % had manifest dm ( . % t dm and . % t dm). glycaemia in all three time-points of baseline ogtt, area under the curve (auc ogtt ) and baseline hba c were significantly associated (p < . , mann-whitney) with the postpartum disorder. using regression analysis predictive risk model was developed using these baseline parameters. conclusions: parameters of glucose metabolism measured during - th week of pregnancy fulfilling criteria of gdm diagnosis exhibited highly statistically significant differences between women with and without persistent postpartum glucose metabolism abnormality and conferred significant predictive potential. considering generally lowcompliance of gdm women any more specific assessment of future risk stratifying gdm population could enable more effective screening of postpartum glucose metabolism disorder. institute of molecular biomedicine, comenius university medical faculty, department of health, bratislava self-governing region, regional public health office, bratislava, slovak republic background and aims: in the adults, microalbuminuria is considered as biomarker of present/future cardiovascular and/or renal disease. the roots of these diseases extend back into childhood/adolescence. data on prevalence of microalbuminuria, renal excretion of albumin (albumin/creatinine ratio, acr) and its relationship to obesity and blood pressure in apparently healthy adolescents are scares. methods and results: fourteen to -years-old apparently healthy students of secondary schools in bratislava district were enrolled (n = , boys: %). acr was determined in a spot urine sample. in underaged subjects overweight/obesity was classified according to age-and sex-based slovak population tables from . blood pressure values were recorded. acr (iqr: . - . mg albumin/ mmol creatinine vs. . - . mg albumin/mmol creatinine, p < . ), and the prevalence of microalbuminuria ( . % vs. . %, chi-square: p = . ) were higher in girls than in boys. prevalence of overweight ( . % vs. . %) and obesity ( . % vs. . %), as well as blood pressure values in pre-hypertensive ( . % vs. . %) and hypertensive ( . % vs. . %) ranges were higher in boys if compared with girls. in underweight subjects, particularly boys, acr was significantly higher if compared with the overweight/obese subjects. acr correlated inversely with the markers of peripheral and central obesity. conclusions: our data suggest the need of specific interpretation of data on acr in the adolescents, and the need of further analysis of this (in the adults risk) marker in population of adolescents with regard to other important determinants of acr, such as insulin sensitivity and other metabolic syndrome risk factors. inclusions criteria were bmi between and kg/m , morbidities as diabetes type more than years in oral treatment and without control, hypertension in oral treatment too, moderate or severe liver steatoses diseases and lipid diseases. results: all patients in a both of groups (laparoscopic and robot approach) had a effective loss of weight, with mean about - kg ( - %) after year period. one case of robot approach presented a staple line bleeding at first postoperative day, without transfusion. morbidity rate after rasg was %, but no gastrointestinal leaks occurs. conclusions: rasg can be a safely and feasible tool to the surgical treatment of obese patients and co-morbidities, with good results and satisfactory outcomes. results: patients were nine males and six females with mean age of years (range - ). seven patients were under insulin treatment and with oral medications only. glycemia at months post-surgery ( . ae . mg/dl; n = ) was significantly reduced (p = . ) compared to time ( . ae . mg/dl). the same occurred with hba c at months ( . ae . %; n = ) compared to time ( . ae . %) (p = . ). bmi was also reduced at month ( . ae . ; n = ) compared to time ( . ae . ) and months ( . ae . ; n = ) compared to time ( . ae . ) (p = . ). only one patient remained under insulin after surgery. the procedure was considered safe and significantly improved metabolic control of non-obese t dm patients, although moderate weight loss was also observed. recent studies have shown that the practice of a proper diet provides health benefits. also, it has been observed that the body weight gain is associated with consumption of unbalanced diets. the objective of this study was to evaluate the quality of the diet in adult residents of tehcnological institute of tepic and establish differences for normal weight (nw) and overweight/obesity (ow/ob). forty two adults > years were evaluated, they were taken anthropometric data for weight, height and body mass index (bmi, kg/m ) was calculated. for the diagnosis of nw and ow/ob, were taken established by world health organization (who). it was used a -day dietary record, for diet analysis was used dial software, which contains tables of food composition mexicans. dietary data were adjusted for the degree of discrepancy between energetic intake and energy expenditure obtained estimate. for statistical analysis was used the program rsigma babel and statistical differences were established < . . the caloric profile was unbalanced in % of the study population: a high consumption of fat in detriment of carbohydrates. the difference between groups were not significant (p > . ) in the caloric profile, but nor in lipidic profile. the analysis of the discrepancy intake/energy expenditure describes a probable undervaluing of the diet in both groups, but higher in adults with ow/ob compared to nw ( patients with long standing diabetes had a higher leptin, hsp , hba c and triglyceride than controls. serum leptin levels were significantly lower in patients with newly diagnosed diabetes. women with type diabetes had a higher leptin levels compared to men, both before and after treatment. we showed a positive correlation between leptin-hsp in women with type diabetes. the correlation was highest in women with newly diagnosed diabetes (r = . ) and was attenuated in women who were on treatment (r = . ). the significance of this correlation was only observed in women with type diabetes. there was no correlation between leptin and hsp in men. the positive correlation between leptin and hsp is observed in chronic inflammation such as type diabetes. it could be hypothesized that the observed correlation between serum hsp and leptin imply a higher state of chronic inflammation. materials and methods: carotid atherosclerosis (measurement of intiamedia thickness -imt) and the presence of steatosis were assesed using ultrasonography in subjects ( . % men and . % women, mean age . ae . years), selected from a rural population (were excluded those with known liver disease and those with alcohol consumption > g/day). results: . % of subjects had different degrees of steatosis: . % mild, . % moderate, . % severe. the metabolic syndrome and all its individual traits, were significantly more frequent in nafld patients, especially in those with severe steatosis (p < . ). the mean value for imt was . ae . mm, increasing in parallel with the severity of steatosis. also, subjects with ms had significantly higher imt values than those without ms (p < . ). in the group without ms, imt mean was significantly higher in patients with steatosis than in those without steatosis (p = . ), and in patients with moderate/severe steatosis than in those with mild steatosis (p = . ). by multiple regression analysis, larger waist circumferince (r = . ), increasing alcohol consumption (r = . ) and the presence of steatosis (r = . ), were significant predicting factors for increased imt. conclusions: these data confirm the hypothesis that the presence of steatosis, independently of the ms, is associated with a significant risk for development of atherosclerosis and its detection should be an alert for the existence of an increased cardiovascular risk. the prevalence of the metabolic syndrome (ms), a cluster of central obesity, hyper/dyslipidemia, hyperglycemia, and hypertension is constantly increasing worldwide. although, the exact mechanisms underlying the development of the ms are not completely understood, modern lifestyle of physical inactivity and unhealthy nutrition, obesity, and their interaction with genetic factors are considered largely responsible. this study was carried out to identify the association between physical inactivity and burden metabolic syndrome diseases (bmsd) in an urban brazilian population. a cross-sectional telephone survey was conducted with adults ( . % men and . % women, mean age . years) in the urban area of belo horizonte, brazil. data from the telephone-base brazilian surveillance system for chronic diseases (vigitel - / ) was used. burden metabolic syndrome diseases (bmsd) was defined as the self-reported of at least two of the following factors: diabetes, dyslipidemia, hypertension and obesity. physical activity (pa) indicators were evaluated in free time (leisure), work, home and transportation domains. sociodemographic, health status and lifestyle habits were also used. odds ratios (or) and % confidence intervals were estimated by multivariate logistic regression. in this sample, . % of participants were physically inactive in all domains and the prevalence of bmsd in the sample was . %. physical inactivity was independently associated with bmsd (or = . ; %ci: . - . ), adjusted to age, schooling, poor selfreported health and gender. in this sample, bmsd is a significant public health problem. the evidence from this study shows that physical inactivity was independently associated with proxy of metabolic syndrome. aim: to assess the prevalence of insulin resistance (ir) and glucose homeostasis alterations (gha) in overweight and obese children and the risk factors for ir and gha. method: we collected data from subjects: girls and boys aged . - . years (median: . ). gha was measured by fasting glucose. glucose ! mg/dl was treated as high normal fasting plasma glucose (hnfpg). ir was estimated by homeostasis model assessment (homa-ir), quantitative insulin sensitivity check index (quicki) and fasting glucose/insulin ratio (fgir). we adopted the following cut-off points for diagnosing ir: homa-ir ! . , quicki . and fgir . . results: table . fasting glucose, insulin and ir-indexes. in obese children we observed a significant (p < . ) positive correlation between homa-ir and age (r = . ), bmi (r = . ), fasting insulin (r = . ), triglycerides (r = . ), crp (r = . ) and a negative correlation with birth weight (r = À . ) and hdl the results provide evidence for an association between pd and sm in the adolescent population, which would mean that depression may influence ms in this group that is more vulnerable to pd due to hard changes typical of their life stage. the aim of this study was to evaluate the electrical activity of the pelvic floor muscles (pfm) in women with polycystic ovary syndrome (pcos) diagnostic and insulin resistance (ir). through a crosssectional study, it was recruited women with pcos. the total pcos patients was divided into two groups according to the presence of ri (group a) and without ir (group b). the diagnosis of ri was made through fasting insulin. the muscle tone (mt) and maximal voluntary contraction (mvc) was evaluated by electrical activity, that it was measured by surface electromyography. among the pcos patents, . % had insulin resistence. there was significant difference between the tone (p = . ) and cvm (p = . ) between groups a and b. the correlation test showed a strong negative correlation between muscle tone and fasting insulin levels in group b (r = À . , p = . ). considering the results, it seems that the presence of insulin resistance may adversely affect the electrical capacity of the pelvic floor muscles. central hospital of the army, cpmc, algiers, algeria the polycystic ovary syndrom is a disorder affecting approximatively - % of reproductive age women. hyperinsulinemia and insulinore´sistance are common features of a larger number of patients affected by pcos. objective: the objective of this study was to characterized the prevalence of the insulinore´sistance in a cohort of algerian women with pcos. methods: a total of patients with evidence of pcos defined by the rotterdam consensus were recruted for a prospective study. all women had a standard oral glucose tolerance test with the mesure of glycemia, insulinemia and shbg. the prevalence of insulinore´sistance grows significantly with bmi (p = . ) but didn't change with age (p = . ). the non hyperandrogenic phenotype is less insulinoresistant ( . % vs. . %). conclusion: in our population of pcos near half of them are insulinresistant and need to be treated in order to avoid metabolic features. the aim of this study was to analyze the parameters of glycemic index (ig) in foods intended for feeding patients with impaired glucose metabolism. for this purpose, a new design selected food products, characterized by a higher nutritional value, that pass attempts technological and toxicological studies and have been classified as human food. the food consisted of inulin, buckwheat, pumpkin seeds, buckwheat hulls, the addition of mulberries, kale and beans. the products were characterized by nutritional value and composition. designed food products were the nature of small snacks, designed to supplement the basic diet and enriching it with ingredients desirable from the standpoint of prevention of civilization diseases. characterized by elevated natural origin and health-related properties. the study took part of healthy, non smokers volunteers between and years of age, with proper blood biochemical parameters. the results allow to characterize these foods as relative low glycemic index and possible to use to enrich the diet in the components with pro-health effect. for all the products the dose and single-serving size consumption was described and proposed. the possible potential changes in glucose levels after consumption were characterized. the results are the test pilot study of the project aimed to the creation of the increased food with bioactive healthy properties and are the result of the first stage of the researchclinically-nutritional studies of those products. financial supported by the ue project nr po ig . . . - / . one of the fastest growing trend in food production is designing of health promoting foods, including so-called bioactive food. only food products enriched with bioactive components of natural origin might be perceived as bioactive. it is highly possible that well established technological process of bioactive foods production leads to obtain products useful in prevention and non-pharmacological treatment of metabolic diseases. the project aims to designing these kind of prohealth food, which would simultaneously be organoleptically attractive to the consumer and be an equivalent of conventional, habitually eaten products. the important aspect of bioactive foods is their antioxidant potential, which positive impact on various diseases (obesity, diabetes mellitus and hypertension) is already well known from prior literature. in the studies the antioxidant capacity of the selected bioactive foods designed in the project was assessed. the method used for assessment of antioxidant potential was orac, as the most widely applied and the most reliable one. the analysis included products from three following groups of enriched foods: fruit and vegetable juices, bakery products and confectionery, and meat products, as well as the corresponding placebo products. most of the products enriched in bioactive components was characterized by significantly higher orac values in comparison to placebo correspondents. the results support the correctness of applied production technology and proper selection of bioactive components. based on the antioxidant potential of new products, one can decided which of them should be use for further controlled clinical trial. background: obesity in adolescent tends to persist into adulthood which associated to metabolic disease thereby increasing mortality and morbidity. objective: to investigate the association between central obesity and inflammation marker, insulin resistance and dyslipidemia in adolescent with central obesity. methods: this study was case-control study, compared central obesity adolescent and normal to hscrp, homa-ir, triglyseride, ldlcholesterol, hdl-cholesterol, and sdldl-cholesterol. results: sixty two adolescent were included, were central obesity and were normal. we found that they were with bmi > kg/m had hscrp level higher compared with non obesity, p-value < . (or: . ; % ci: . - . ) and homa ir, p-value < . (or: . ; % ci: . - . ). adolescent with wc ! cm for boys and ! cm for girls, had hscrp levels, homa-ir and hdlcholesterol higher than they were with wc < cm, p-value < . (or: . ; %ci: . - . ), p < . (or: . ; %ci: . - . ) and p-value < . (or . ; %ci: . - . ), respectively. the visceral fat was associated with hscrp levels, p < . (or: . ; %ci: . - . ), and hdl cholesterol p < . (or . ; %ci: . - . ). triglyceride and sdldlcholesterol had not significanty for bmi, wc and visceral fat, however ldl-cholesterol significantly association with visceral fat, p < . (or: . ; %ci: . - . ). conclusion: central obesity adolescents showed increased inflammatory markers and insulin resistance with consequent increased the risk of metabolic diseases so that early intervention in obese adolescents should be done. aims: consumption of high fat diet (hfd) leads to accumulation of intramuscular ceramide (cer). cer is implicated in induction of muscle insulin resistance. the initial step in the de novo cer synthesis is catalyzed by serine palmitoyltransferase (spt). the aim of the present study was to elucidate the role of hfd, myriocin (an spt inhibitor) and metformin on the content of skeletal muscle cer and key proteins implicated in lipid and glucose metabolism in hfd insulin resistant rats. the experiments were performed on male wistar rats, divided into groups: cfed standard rodent chow (control); hfdfed high fat diet; hfd/myrfed hfd and treated with myriocin; hfd/myr/metfed hfd and treated with both the myriocin and metformin. muscle cer and plasma free fatty acids (ffa) were analyzed by lc/ms/ms. content of spt, carnitine palmitoyltransferase (cpt a), fatty acid transporters (cd , fabppm) and glucotransporter (glut ) was measured by wb. results: compared to control values, plasma ffa and muscle cer content and expression of all lipid-related proteins were elevated in hfd group. myriocin decreased muscular cer but increased plasma ffa and the expression of both the spt and cpt a. introducing metformin to hfd/myr group decreased the plasma ffa and muscular cer, lowered the expression of spt, cpt a, cd and fabppm, but increased muscular glut expression as compared to hfd and hfd/myr group. conclusions: simultaneous treatment with myriocin and metformin decreases the plasma ffa and muscular cer and improves glucose tolerance by augmentation of muscle glut expression. internal medicine, new london hospital, new london, nh, usa hyperglycemia, and hyperlipidemia. understanding whether side effect profiles differ between the most commonly prescribed agents could greatly inform prescribing decisions. objectives: to quantify differences in weight gain and metabolic side effects between aripiprazole, quetiapine, and risperidone in adults and children requiring chronic antipsychotic therapy. selection criteria: randomized controlled trials that compared at least two of the three atypical antipsychotics of interest and reported change in weight. all dosing ranges were included and there were no age or diagnosis restrictions. data collection and analysis: two blinded clinicians independently completed data extraction with a piloted, standardized data collection form. study quality was assessed through the cochrane risk of bias tool. we calculated weighted mean differences (wmd) and % confidence intervals (ci) using random effects models on review manager . main results: of studies identified through our search, published trials involving study participants met full inclusion criteria. quetiapine resulted in more weight gain than risperidone and risperidone resulted in more weight gain than aripiprazole). no trials directly compared aripiprazole to quetiapine, but an indirect method of comparison demonstrated that quetiapine causes more weight gain than aripiprazole. similarly, quetiapine led to a greater increase in glucose levels, a greater increase in blood pressure, and a greater increase in total cholesterol than risperidone. non insulin dependent diabetes mellitus (niddm) as a most common form of diabetes is a major public health problem; there is a subgroup of niddm patients which develops the disease at an early age and shows a dominant mode of inheritance. this type is nominates maturity onset diabetes of the young (mody). the prevalence of mody is difficult to access as patients with mody genes mutations are often identified during routine screening for other purposes. mody was linked to mutations in glucokinase gene (gck), and account for - % of mody, with the highest prevalence being found in the southern europe. the aim of this study was to examine the prevalence and nature of mutations in gck gene in iranian paients. we have screened gck mutations by single stranded conformation polymorphism (sscp) technique of polymerase chain reaction (pcr) in iranian families with clinical diagnosis of mody, included patients (eight males and females) and their family members. pcr products with abnormal mobility in denaturing gradient gel electrophoresis (dgge) were directly sequenced. we identified six novel mutations in gck gene in iranian families (corresponding to . % prevalence). our findings and the last study on mody highlight that in addition to gck, other mody genes such as mody and modyx may play a significant role for diabetes characterized by monogenic autosomal dominant transmission. this is clear that the knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing mody. background: several epidemiological studies proposed an association between helicobacter pylori (h. pylori) infection with insulin resistance (ir) and metabolic syndrome (mets). however, up to date there is no conclusive evidence regarding this association. objectives: to investigate the prevalence and correlates of h. pylori infection among lebanese adults and to evaluate its association with ir and mets. materials and methods: stored blood samples of adults participating in the national nutrition and non-communicable diseases risk factors survey conducted in lebanon were used for this study (n = ). h. pylori-specific immunoglobulin g antibody titers were measured by elisa. data available included, in addition to anthropometric measurements, sociodemographic and lifestyle characteristics, blood pressure, biochemical indices (serum insulin, hdl, ldl, tag, glucose). a homa -ir level was used to assess insulin resistance. the international diabetes federation criteria were used to classify study participants with mets. results: the prevalence of h. pylori infection in the study sample was % ( % ci: . - . %). a higher crowding index was associated with a % increase in the odds of infection (or: . , ci: . - . ). blood pressure, waist circumference, serum hdl, ldl, tag, and glucose levels were comparable between h. pylori positive and negative subjects. the odds of ir and mets were not significantly different between the two groups. comparable to other developing countries. furthermore, our findings suggested no association of h. pylori infection with ir or mets. eradication of h. pylori infection to prevent ir or mets is not warranted. the economic burden resulting from diabetic neuropathy (dn) consumes a major portion of resources allocated for health-care services. the present study was undertaken to assess the costeffectiveness of medical intervention in patients with dn. two hundred patients with dn were purposively selected from out-patient department of birdem hospital, bangladesh. of them were late in detection of dn (ldn) and were detected early (edn). in ldn group, % had diabetic peripheral neuropathy (dpn), % had diabetic autonomic neuropathy (dan), % had diabetic proximal neuropathy (dpxn) and % had diabetic focal neuropathy (dfn). in edn group, % had dpn and % had dan. the average annual cost of care was us$ (direct us$ and indirect us$ ), with an average us$ per patient. among the average annual cost ldn consumed us$ (us$ per patient) and edn us$ (us$ per patient). the annual medical costs increased with the increased number of complications from us$ to to and to in ldn with one, two, three and more than three complications which is increasing at a rapid rate and us$ to to and to in edn respectively, increasing at a diminishing marginal rate. the regression equation showed that medical cost is significantly related to complications tested in both univariate (p < . ) and multiple linear regression analyses (r = . ; f- . , p < . ). proper management with regular screening substantially reduces the expenditure related to care and complications. a. alizadeasl , z. ojaghi-haghighi , r. azarfarin tabriz university of medical sciences, tabriz, rajaei hospital, tehran, iran background: metabolic syndrome (ms), the combination of hypertension obesity, dyslipidemia, and insulin resistance, is a precursor of diabetes mellitus (dm) and highly prevalent among patients with acute myocardial infarction (ami). diabetes mellitus is associated with larger infarct size and worse outcomes after ami. this study examind the clinical presentation and hospital outcomes among nondiabetic patients with ms following ami. this investigation is prospective analytic study (cohorts type) in consecutive infarct survivors who admitted to our heart centers through years ( ) ( ) ( ) . patients with diabetes (n = ) were excluded. those with ms (n = ) included patients with three or more of the following criteria: hypertension, elevated fasting blood glucose, hypertriglyceridemia, low high-density lipoprotein, and obesity [body mass index (bmi) >or = ]. the control group (n = ) included patients without ms or dm. results: baseline characteristics were similar except for hypertension, bmi, and dyslipidemia, which by study desing were higher in the ms group. the nondiabetic ms group had larger left ventricular dimension (p = . ), left atrium dimension (p = . ) and higher rate of ejection fraction % ( % vs. %, p < . ). also nondiabetic ms patients had higher rates of in-hospital death ( . % vs. . %, p < . ); post infarction angina ( . vs. . , p < . ) and more frequent left main coronary artery or three-vessel disease than the control group ( . % vs. . %, p < . ). conclusion: nondiabetic metabolic syndrome is common in patients with ami and strongly associated with poor outcome of them. background: this study assessed the prevalence of the metabolic syndrome (ms) and its impact on hospital outcomes in patients with acute myocardial infarction (ami) using both ncep atp iii and idf definitions. this investigation is propective analytic study (cohort type) in consecutive ami survivors (mean age: . ae . years; men and women), who admitted to our heart centers through years ( ) ( ) ( ) . results: q-wave myocardial infarction (mi) was present in . % of patients and non-q-wave mi, in . %. the ms was found in . % of the patients and was significantly more common in women than in men ( . % vs. . %, p = . ). one component of the ms was found in . % of patients; two, in . %; and none, in . %. . % of the patients had four or five components. hypertension was the most common component of the ms ( . %). . % of ms patients had triple-vessel disease on coronary angiography in comparing with . % in non-ms, ami patients (p < . ). the ms group had larger infarct size as determind by peak creatine kinase-mb ( . ae . vs. . ae . , p < ). overal inhospital complications (mechanical and electrical) were higher in patients with ms ( . % vs. . %, p = . ). ms is associated with a . -fold increased risk of acute renal failure after mi (p = . ). conclusion: ms in patients with ami is prevalent and associated with larger infarct size, more in-hospital complications, and marked increase of acute renal failure. background and aims: according to current views metabolic syndrome (ms) and obesity, especially with increased amount of visceral fat is characterized by prothrombogenic changes of hemostasis and fibrinolysis. methods: cross-sectional observational study included postmenopausal women (age - ) with ms. coagulant system was assessed by measurement of parameters of plasma haemostasis [activated partial thromboplastin time (aptt), fibrinogen concentration], and the activities of coagulant factors vii (fvii), viii (fviii) and ix (fix) in plasma. in order to investigate the functioning of anticoagulant system the activities of antithrombin iii. also we assessed adiponectin (adp) and homocysteine (hm) concentrations in plasma. results: prothrombotic alterations were observed in . % women. the aptt was decreased in . %, hyperfibrinogenemia was revealed in . %, the increased activity of: fviiin . %, fviiiin . %, fixin . %, and the decreased activity of antithrombin iiiin . %. the hm levels was increased in . %, the adp levels was decreased in . %. there were a significant positive associations between some of revealed prothrombotic alterations (fvii, fviii and fibrinogenemia) and anthropometric markers of visceral obesity and ms (weight, body mass index, and waist circumference). the adp levels were inversely correlated with the hm levels (r = À . , p < . ) and the activity of fvii (r = À . , p < . ). conclusion: results of our study demonstrate high prevalence of various prothrombogenic abnormalities in coagulation and anticoagulation systems in patients with visceral obesity and ms. plasma b-type natriuretic peptide (bnp) and blood urea nitrogen (bun) are elevated in heart failure. renal function is known to be an important factor related to bnp and bun determination. the aim of the present study was to examine whether bnp and bun are associated with left ventricular diastolic dysfunction (lvdd) in patients with type diabetes (t dm) without chronic kidney disease (ckd). the subjects in this study were consecutive patients with t dm [ men ( %); age ae years old (mean ae sd); diabetic duration ae years; hba c . ae . %]. subjects with overt heart failure or nyha class > , history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, and estimated glomerular filtration rate < ml/min/ . m were excluded from the study. all patients underwent clinical evaluation, laboratory tests including bnp determination, and echocardiographic examination. doppler echocardiographic indices including peak early diastolic mitral annular velocity (e′) and early diastolic myocardial velocity (e) were obtained in each patient. none of the patients exhibited systolic impairment of left ventricular function (ejection fraction > %), whereas lvdd (e/e′ > ) was detected in cases ( . %). e/e′ correlated with age (r = . , p < . ), sex (r = . , p = . ), diabetic retinopathy stage (r = . , p = . ), systolic blood pressure (r = . , p = . ), bnp (r = . , p = . ), and bun (r = . , p = . ). in multiple regression analysis, age (b = . , p = . ), sex (b = . , p = . ), bnp (b = . , p = . ), and bun (b = . , p = . ), correlated independently with e/e′. bnp and bun could be useful tools to screen for preclinical ventricular diastolic dysfunction in patients with t dm without ckd. h. kawano, y. nagayoshi, y. kinoshita objective: this study compared the effects of combination statin and fibrate therapy with either statin or fibrate monotherapy on lipid profiles in patients with impaired glucose tolerance (igt) and a high risk for cardiovascular disease. methods and patients: forty-five patients with igt and dyslipidemia (men , women , mean age . ae . years) were assigned randomly to the three treatment groups for a -month period. results: after months of treatment, low density lipoprotein levels decreased in every group, especially the statin and statin + fibrate groups. triglyceride levels also decreased in all three groups, especially the fibrate and statin + fibrate groups. high density lipoprotein cholesterol and fasting blood glucose levels did not change in any group. the levels of remnant like cholesterol particles decreased in the fibrate and statin + fibrate groups. there was no change during the study in the levels of creatine phosphokinase, lactate dehydrogenase, or creatinine. conclusion: combination statin and fibrate therapy results in greater improvement in lipid profiles than monotherapy with either drug. no marked adverse effects were observed with combination therapy during the study. background: gout is considered a metabolic disease and ranked among the diseases connected with obesity, such as an arterial hypertension, coronary artery disease, stroke, and type diabetes mellitus (who, ) . it has been proven that intake of a considerable quantity of meat products is predictor of acute gouty arthritis. for this reason there is great interest in studying the prevalence of gout among inhabitants of the republic of sakha (yakutia) where a lipid-protein diet prevails. this is a preliminary report on the incidence of gout requiring hospitalization in - . objectives: patients hospitalized in the yakut city hospital with gouty arthritis were studied. methods: patients are being studied by means of a questionnaire developed by the institute of rheumatology (moscow). results: forty-four patients were registered ( men and two women). the majority of patients (n = ) are inhabitants of yakutsk city. median age of the subjects is years, with a range of - years; four patients are over . secondary forms of gout and relapses of disease are common. accompanying pathology includes: ah in patients, cad in seven patient, type dm in four patients, glucose intolerance + obesity in one patient, metabolic syndrome + obesity in one patient, uncomplicated obesity in one patient, metabolic syndrome without obesity in one patient, chronic renal insufficiency in one patient, and cardiovascular accidents in three patients. the research proceeds. results will be used for characterization of the incidence and diagnostic features of gout in yakutia especially among young patients with accompanying metabolic abnormalities. background: the prevalence of obesity, a major public health problem, is rising in many countries including iran. non-drug dependent interventions for obesity management include physical activity, dietary restriction and acupuncture. primary study objective: we examined the effects of body electroacupuncture and low-calorie diet on plasma leptin in obese and overweight individuals with the excess or deficiency pattern (according to chinese medicine). methods/design: the case group received authentic electroacupuncture and the placebo group received sham acupuncture. both groups consumed a low-calorie diet for weeks. settings: this study was conducted in nutritional clinic of ghaem hospital, mashhad, iran. participants: people (n = ), aged between and years with body mass indexes (bmi) between and kg/m were randomized into two groups. interventions: comparison of either real or shame electro acupuncture combined with a low caloric diet was investigated in this trial. primary outcome measures: plasma leptin, body fat mass (bfm), body weight and body mass index were measured before and after treatment. results: in volunteers in the case group with both the excess and the deficiency patterns, we found a significant reduction in plasma leptin ( . %, p = . ) and bfm ( . %, p = . ). in the placebo group, we found a less significant reduction in leptin and bfm. the difference between the two groups was significant for leptin (p = . ) but not for bfm (p = . ). conclusions: body electroacupuncture with a low-calorie diet may reduce plasma leptin concentration; through a mechanism that will require further clarification. m. darbandi , , s. darbandi , , a.a. owji , p. mokarram , m. ghayour mobarhan effects of auricular acupressure combined with low-calorie diet on the leptin hormone level. methods: volunteers (n = ) with body mass indexes (bmi) between and kg/m were randomised into a case (n = ) or a control (n = ) group. the participants in each group received a low-calorie diet for weeks. the case group was treated with auricular acupressure and the control group received a sham procedure. plasma leptin levels, body fat mass, body weight (bw) and bmi were measured before and after treatment. results: participants who received auricular acupressure showed significant reductions in their plasma leptin levels ( . %, p < . ) as well as in their body fat mass ( %, p < . ). these changes were not observed in the control group. the reduction in leptin was significantly greater in the acupressure group than the controls. conclusion: auricular acupressure combined with a low-calorie diet significantly reduced plasma levels of leptin. however, the mechanism of this reduction is not clear. background: premature arteriosclerosis may be one of the mechanisms linking pre-diabetes mellitus (pre-dm) and cardiovascular disease. we assessed premature arteriosclerosis in pre-dm using arterial stiffness indices and analyzed the associated contributors of this process. methods: we collected clinical data of patients without dm, pre-dm patients, and dm patients. both the compliance index (ci) and stiffness index (si) were measured to indicate large and peripheral arterial stiffness. results: patients with pre-dm and dm had lower ci ( . ae . vs. . ae . units; p < . and . ae . vs. . ae . units; p < . , respectively) and higher si ( . ae . vs. . ae . m/s; p < . and . ae . vs. . ae . m/s; p < . , respectively) than patients without dm. both pre-dm and dm patients had higher glucose and hemoglobin a c , higher homa index, higher hscrp, and a lower adiponectin level than patients without dm. using multivariate linear regression analysis, age, heart rate and homa index were independent determinants for si (whole model: r = . , p < . ), whereas male gender, hscrp, and homa index were independent determinants for ci (whole model: r = . , p < . ). conclusions: homa index was an independent determinant for arterial stiffness. increased insulin resistance may associate with increased arterial stiffness both at large and peripheral arteries in pre-dm patients. king's college london, london, uk, uppsala university, regional cancer centre, uppsala, sweden, guy's & st thomas' nhs foundation trust, london, uk, karolinska institute, stockholm, sweden background: impaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. we used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer. methods: we selected , persons (> years old) with four prospectively collected serum glucose and fructosamine measurements from the apolipoprotein mortality risk (amoris) study. multivariate cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer. results: a positive trend was observed between standardized log overall mean glucose and overall cancer risk (hr = . ; % ci: . - . ). including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and a statistically significant protective effect of fructosamine (hr = . ; % ci: . - . and hr: . ; % ci: . - . , respectively). the highest risk for cancer was among those in the highest tertile of glucose and lowest tertile of fructosamine. similar findings were observed for prostate, lung, and colorectal cancer. the contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors. patients in two groups were compared according to age, parity, prepregnancy weight, family history of diabetes mellitus, history of macrosomia in their previous pregnancies, history of hypertension, previous malformed fetus, history of iufd and abortion. based on the obtained results there was a statistically significant difference between two groups in terms of age (p < . ), parity (p < . ), prepergnancy weight (p < . ), family history of diabetes mellitus (p < . ), previous macrosomia (p < . ), history of hypertension (p < . ), previous malformed fetus (p < . ) and previous iufd (p < . ), but abortion was not significantly different. older age, parity (three or more) obesity, family history of diabetes mellitus, history of macrosomia, hypertension, malformed fetus and also previous iufd are risk factors for gestational diabetes. therefore, these women should be screened and handled for gestational diabetes in their pregnancies, and controlled for possible diabetes mellitus in the future. methods: this family based study was conducted on nuclear families from among tehran lipid and glucose study with two biological parents and at least two offspring ( parents and offspring), aged - years. selected families had at least one person with overweight or obesity. all obesity-related variables (height, weight, hip, waist circumference (wc), body mass index (bmi), body size (bs), resting energy expenditure (ree), waist to hip ratio (whr)) were measured and calculated. the heritability estimate of continuous variables was calculated using a standard quantitative genetic variance-components model which was implemented in the solar software. results: the heritability estimates for obesity-related variables such as height, weight, hip, wc, whr, bmi, bs, and ree, after adjustment for sex, age were %, %, %, %, %, %, %, and %, respectively. the h for the above mentioned variables, expect of bs, after adjustment for sex, age, and body size varied to %, %, %, %, %, %, and %, respectively (p < . ). we clearly demonstrated a significant heritability of obesity-related variables among tlgs families. the results of the present study confirmed the important impress of genetic factors on the obesity-related variables phenotype. method: pwv determined with bpuls apparatus using left external carotid and left dorsalis pedis arteries as "central" and "peripheral" points respectively. pulses picked up by infrared sensors and recorded simultaneously with single lead ecg. time difference between pulses measured. shorter time delay or faster pwv indicates decreased arterial elasticity. materials: nine hundred and fifty-seven asymptomatic filipinos studied. males- , females- . age - years. three hundred and twenty-seven hypertensives. classified into groups according to bmi and wc. average pwv time (adjusted for height) for each group noted. relationship of increased bmi and wc to variations in pwv time determined. results: elevated bmi does not significantly influence pwv time in: all subjects-(p < . ); females-(p < . ); normotensives-(p < . ); and, hypertensives -(< . ). however, for every centimeter increase of wc there is a corresponding decrease of pwv time by: . s (p < . ) in all subjects; . s (p < . ) in females; . s (p < . ) in normotensives; and, . s (p < . ) in hypertensives. discussion: abnormal pwv is a high cvd risk factor. in four groups above, elevated bmi does not significantly influence pwv time. however, in the very same groups, increased wc significantly affects pwv time. this indicates that if we rely solely on bmi to predict cvd we will miss cases which are at high risk as shown by abnormal wc. correlation (r = . ). an increased risk of cvd and cancer was identified with elevated levels of ggt or crp or both markers (ggt-crp score ! ); the greatest risk of cvd and cancer was found when ggt-crp score = (hr: . ( %ci: . - . ) and . ( . - . ) compared to ggt-crp score = , respectively). conclusion: while ggt and crp have been shown to be associated with metabolic abnormalities previously, their association to the components investigated in this study (hyperglycaemia and dyslipidaemia) was limited. results did demonstrate that these markers were predictive of associated diseases, such as cancer and cvd. metabolic syndrome is the aggregation of conditions that together increases the risk of cardiovascular disease and diabetes mellitus in both normal glucose tolerance (ngt) and impaired glucose tolerance (igt) subjects. it is estimated that around - % of the world′s adult population have the metabolic syndrome. over the last years the prevalence of metabolic syndrome has steadily increased in all populations, and making it one of the major global public health challenge. the objective of this study is to estimate the prevalence of metabolic syndrome and cardiovascular risk factors in impaired glucose tolerance (igt) subjects. two hundred and four impaired glucose tolerance and normal glucose tolerance subjects of both genders were selected for the present study according to the american diabetes association ada criteria, on the base of h glucose tolerance test. anthropometric characteristics like waist circumference, bmi, systolic blood pressure, and diastolic blood pressure were measured with standard techniques. biochemical parameters like fasting blood sugar, fasting insulin, cholesterol, triglycerides, hdl-c, and ldl-c were determined by standard techniques, the homa-ir values were calculated with the help of formula. it is concluded from the present study that the prevalence of metabolic syndrome is significantly increased according to aace, atpiii definition criteria's in impaired glucose tolerance subject, the study emphasizes strongly that ms is major factor to enhance the incidence of type diabetes and cardiovascular diseases in impaired glucose tolerance subjects. it is suggested that preventive measures and treatment can reduce incidence of cvd, type diabetes in our population. anthropology, vidyasagar university, midnapore, india waist circumference (wc) and waist-hip ratio (whr) were reported as imperative abdominal obesity related measures having influence on many cardiovascular disease (cvd) risk factors. present study attempts to evaluate the possible association of abdomen circumference (ac) with hypertension and dyslipidaemia among the bhutias, a tribe residing the sub-himalayan state of sikkim, india. five hundred and eleven bhutias of both sexes aged ! years inhabiting gangtok, the state capital and its neighbourhood were systematically selected to participate in the study. after providing informed consent data on blood pressures, blood lipids, anthropometrics and other lifestyle related variables such as perceived stress, diet, energy expenditure, socioeconomic status and so on were collected following standard methods. the results evidently indicate that the ac is the best predictor of the selected cvd risk factors. after log transformation, the effect of age on cvd risk factor variables and anthropometrics was found and regressed out through linear regression. data was pooled for sex as significant sex difference was absent for most of the variables. after adjusting for significant lifestyle related predictors, multiple logistic regression was carried out to evaluate the significant obesity related predictors of hypertension and dyslipidaemia. receiver operating characteristic (roc) curve finally showed ac as the best predictor of hypertension and dyslipidaemia. although wc and whr were found to be important abdominal obesity related predictors of cvd risk factors in many studies, present population based cross sectional study has proved the importance of considering ac as a central obesity related predictor of different cvd risk factors. the achievement of therapeutic goals is of great importance in patients with chronic diseases such as diabetes mellitus (dm), because of its impact on morbidity and mortality. objective: to explore the relationship between therapeutic adherence and metabolic control in patients with dm- , who were seen at a hospital in the city of medellı´n (colombia). methods: cross-sectional study involving patients with the following selection criteria: age ! years, diagnosis of dm- ! months, who signed informed consent. the summary of diabetes self-care activities (sdsca) score was applied for the measurement of therapeutic adherence and duke-unc score for the assessment of perception of social support. glycosylated hemoglobin (hba c) was processed by turbidimetric inhibition immunoassay (tinia) cobas c- equipment. adequate metabolic control was defined as value of hba c %. version . of the spss program was used for the statistical analysis. results: seventy patients studied: % are female, % suffer from hypertension, % have dyslipidemias and % smoke. in addition, % are insulin dependent, % have inadequate glycemic control and % has no social support. items with the highest proportion of adherence were: medication ( %), foot care ( %) and diet ( %). whereas the lowest were: hba c ( %) and exercise ( %). hba c correlated significantly (p < . ) with adherence to diet, blood glucose monitoring, foot care, social support and sex. conclusion: therapeutic adherence was associated with metabolic control in patients with dm- . mellitus. however, it is unclear if severity of dr is associated with lvdd, which is recognized to result in subsequent heart failure. the subjects in this study were consecutive patients with type diabetes mellitus (t dm). all patients underwent clinical evaluation, laboratory tests, and echocardiographic examination. doppler echocardiographic indices including peak early diastolic mitral annular velocity (e′) and early diastolic myocardial velocity (e) were obtained in each patient. the patients were divided into three groups according to presence of dr and its severity: no diabetic retinopathy (n = ), simple retinopathy (n = ), and preproliferative or proliferative retinopathy (n = ). no patients showed systolic impairment of left ventricular ejection fraction (lvef > %), whereas impaired lv diastolic function (e/e′ > ) was detected in cases ( %), furthermore lvdd (e/e′ > ) was detected in cases ( %). e/e′ was correlated with age (r = . , p = . ), sex (r = . , p = . ), diabetic duration (r = . , p = . ), dr stage (r = . , p = . ), systolic blood pressure (r = . , p = . ), and serum creatinine level (r = . , p = . ). in multiple regression analysis, age (b = . , p < . ) and dr stage (b = . , p = . ) were independently correlated with e/e′. in this study, we showed that almost all subjects had asymptomatic lvdd, and severity of dr was associated with lvdd in patients with type diabetes mellitus. objectives: this study explores the contribution of the sasang constitutional types as a risk factor for hypertension by examining the prevalence and risk for hypertension across different constitutional types (se, sy, te, and ty types) and investigating whether certain constitutional types can increase the risk of hypertension in an individual. design: this retrospective chart review evaluated the charts of patients who had visited the clinic for routine physical check-up. subjects: among , visitors, those aged between and , with complete data concerning the past medical and social history, blood pressure and body size measurements, results of blood test, and confirmatory constitutional typing (excluding the ty type) were included in the final analysis group (n = ). results: especially, even after adjusting for the different variables, the odds ratio for hypertension in the te type was found to be . (ci . - . ) (taking the se type as the reference group), indicating that the te constitutional type can act as a risk factor for hypertension. moreover, when comparing the te type to non-te types, the odds ratio was found to be . (ci . - . ), implying a weak but valid contribution of the te constitutional type toward increasing the risk of hypertension. the results of this study show that the prevalence of hypertension differs across different constitutional types, and that the constitutional type (the te type) can act as a risk factor for hypertension independently of other possible variables. a.b. shetty , p.k. roy physical therapy, university of st mary, leavenworth, ks, bon secours hospital, baltimore, md, usa introduction: the purpose of this research was to determine whether habits of individuals contributed to changes in metabolic rate. as the daily physical activity levels increase, there is an increase in the metabolic rate and caloric expenditure. it can be inferred that people who are overweight may not participate in physical activities due to social, psychological, and physical reasons. they may spend more time in less physically demanding activities during their leisure time. hypothesis: it was hypothesized that the individuals who like to read for pleasure during leisure will have higher body-mass-index. subjects: a group of college aged, - , females volunteered to be the subjects for the study. method: each subject's weight and height were collected to determine bmi. the leisure time activities that were included were reading, sleeping, watching television, use of computers, and sports and physical activities. a likert scale questionnaire was developed and had four levels of answers for each of the leisure time activities. a person-product moment correlation was used to determine the relationship between bmi and five leisure time activities. the results indicate that a positive correlation of . between bmi and leisure time reading habits. there is a negative correlation of À . between bmi and sports and physical activities. conclusion: this research demonstrates that the bmi is significantly higher for individuals who like to read during their leisure time activities. therefore, it is also important to develop physical activities as habits during early years that may carry into adulthood. objectives: the main goal of this retrospective cohort study was to compare the incidence of over-all and site-specific cancers among israeli arabs with diabetes mellitus (dm) with that of israeli arabs without dm. methods: a retrospective cohort study was conducted in northern israel, involving all arab subscribers of clalit healthcare services (chs), which is the major hmo service in the region, serving over % of the concerned population. results: during a period of years ( - ) of follow-up, and incident cases of cancer were found among , people with dm and , adults free of dm, respectively. the follow-up time involved , person years. dm was associated with a standard incidence ratio (sir) of . ( %ci: . - . ) and . ( %ci: . - . ) for pancreas cancer in men and women, respectively. a significantly reduced sir was observed for esophageal, stomach and intestine cancer . ( %ci: . - . ) in men. our findings support an association between dm and increased risk cancer of the pancreas in arab men and women. a significantly reduced risk of all other cancers was observed only in arab men. a.e. berezin , o.a. lisovaya methods: seventy-two mild-to-moderate arterial hypertension patients within - weeks after ischemic stroke were enrolled to the scrutiny at baseline. both vegf- and mmp- plasma levels were measured at the study entry and in months after baseline by elisa. we has been assessed all new cardiovascular events including myocardial infarction (mi), unstable angina (ua), recurrence stroke (rs), tia, advance heart failure (hf) during study period. results: analysis of obtained outcomes have been shown that all cases (n = ) of new cardiovascular events identified during first weeks after start of observation are correlated well with vegf- plasma levels (r = À . ; p < . ) measured at baseline. on the other hand, -weeks survival rate was . % and . % respectively for group subjects (p < . ) with top and low quartile of vegf- plasma level at baseline. however, lack of tightly interrelationship between cardiovascular outcomes and vegf- (r = . ; p = . ) in months after study entry. the mean mmp- plasma levels were significantly higher in dead patients in comparison to survival subjects of the study end. both new events associated with rs and tia incidences independently study period are correlated well with vegf- (r = À . ; p < . and r = À . ; p < . respectively) only. we has been proposed that circulating vegf- might have more predicting value in comparison with mmp- concentration among hypertensive patients during early ischemic stroke period. introduction: clinician should change the health care system from on diseases treatment to prevention of diseases. obesity increase mortality, morbidity and psychological problems through life but beneficial effects of risk reduction by changing life style have been documented. objective: sedentary life style is the most important factor for promoting weight gain in people. it's clear that obesity occurs when calorie intake exceeding calorie output. obesity is common in families but seems environmental factors can affect body weight beside genes role. a main factor of life style change is energy balance. we recommend one simple healthy life guideline for managing of environmental factors in obese people that includes a diet and physical activity program. body weight should be reduced - % during first year by following of this guideline and continued until achieving to optimal body weight. obese people are visited and monitored some parameters for program adjusting and changed each item basis on individual response. objective: to assess trend and associations between blood sugar level, blood pressure, overweight/obesity and lifestyle among tribe of northeast india experiencing transition. method: cross-sectional study was carried out among tangkhul nagas, aged between and years. subjects were divided into five decadal age groups to assess age trend in biological and socioeconomic variables. height, weight, waist circumference, hip circumference, random blood sugar level, bp, bmi, wsr and whr were evaluated. result: the prevalence of prediabetes and diabetes were . % and . % respectively. diabetes was found among older age groups only. hypertension was highly prevalent with higher percentage among males ( %) than females ( . %). mean bp was higher among males but sugar level among females, which corresponds to their higher adiposity level. prevalence of overweight/obesity in females was . % while in males, it was . %. sugar level and bp had positive correlation with age, bmi, wsr and whr. the prevalence of hypertension and prediabetes/diabetes were higher among centrally obese subjects. central obesity indices were stronger predictors of diabetes and hypertension than general obesity. odds ratio showed urbanization, higher socioeconomic status and sedentary lifestyle as significant risk factors for development of overweight/obesity, which in turn was risk factor for development of diabetes and hypertension. conclusions: tangkhul nagas has been experiencing socioeconomic and lifestyle change which led to the increasing prevalence of overweight/obesity and cardiometabolic health problems, contributing to the escalating global epidemic of obesity and metabolic syndrome. there was close associations between socioeconomic status, age, overweight/obesity, hypertension and blood sugar level. background and aims: trace elements play an essential role in metabolism of carbohydrates, lipids, etc. these results stipulated the present work. we studied patients (eight females, males, age - years) with type diabetes mellitus. duration of the disease varied from month to years. as a control data the hair composition of practically healthy individuals (n = ) were used. as an analytical method instrumental neutron activation analysis (inaa) was used. results: data obtained shows statistically significant decrease of cu, cr, and zn and increase of na, fe, br, and sb levels in hair in the group with a blood glucose concentration < mmol/l. in the group with a blood glucose concentration more than mmol/l levels of cu and la were decreased and na, fe, co, br, and i levels increased. in the group with a blood glucose concentration more than mmol/l glucose concentration correlates with sc (r = . ), cr (r = À . ), and mn (r = + . ). conclusion: it was found that mn level in blood increases with diabetes. this may be a manifestation of mn metabolism dysfunction in diabetes and excretory role of hair. it is also confirms the important role of some elements, especially cr, in diabetes. concentration of this element significantly decreases especially in the first year of illness. unexpected are correlations for sc. usually sc is considered as an element that has no biological role. these findings are additional reasons to study the biological role of less studied ultra trace elements. objective: investigate the prevalence of hyperglycemia in patients undergoing coronary angiography. methods: six hundered and ninety-five consecutive brazilian subjects undergoing coronary angiography were assessed for fasting plasma glucose and hba c (hplc) levels and for previous history of diabetes mellitus (dm). we classified those without previous diagnosis in three groups according to hba c levels (hplc): normoglycemic (n); hba c -< . %; prediabetes (pd) -hba c . % À . %; and dm (d) -a c ! . %. cad defined by any visible lesion ! %. we also classified glycemic status using fasting glucose levels by ada criteria. results: patients were aged . ae . years, . % male. the group had a high prevalence of cardiovascular risk factors: dyslipidemia - %, hypertension - %, % overweight/obese, metabolic syndrome (idf) in % of subjects. cad was detected in . % of them. dm was newly diagnosed using hba c in . % of the whole sample ( individuals) and pd in ( %). in those without dm according to hba c, ( . %) had glucose levels ! mmol/l and ( . %) had glucose ! . mmol/l. in this particulary population with coronary artery disease and/or cardiovascular risk factors we observed a high prevalence of undiagnosed hyperglycemia -dm or prediabetes ( - %) depending on the criteria used for identification/diagnosis (fasting glucose or hba c). this finding reinforces the importance of implementing a systematic screening for hyperglycemia in this high risk population. national university of singapore, singapore, singapore, university of sydney, sydney, nsw, australia objectives: to evaluate associations between metabolic syndrome (mets) components and mortality and whether these associations change over time. methods: three thousand eighty-six eligible residents aged ! years were prospectively followed in the blue mountains eye study, west of sydney, australia. mets components were measured at baseline ( - ) , and after -years and -years ( - ) . using cox proportional hazards and competing risks models with mets as a time-dependent covariate, we estimated effects of mets on all-cause and cause-specific mortality. receiver operating characteristic (roc) curve analyses were used to identify which individual or combined mets components best predicted mortality. . roc analysis suggested that glucose, body mass index (bmi) and blood pressure (bp) best predicted all-cause and chddeath, bmi and bp best predicted stroke-death and glucose and triglycerides best predicted cancer-death. national university of singapore, singapore, singapore, university of sydney, sydney, nsw, australia objectives: to investigate the effect of metabolic syndrome (mets) and its components on the incidence of different sub-types of cataract (cortical, nuclear and posterior subcapsular cataract (psc)) over years and whether these associations change with time. methods: a prospective cohort of elderly aged ! years were followed up over a period of -years in the blue mountains eye study, west of sydney, australia. mets components were measured at baseline ( - ), -years ( - ) and -years ( ) ( ) ( ) . the incidence of different types of cataract was obtained from standard photographic grading at -and -year (n = ). using random-effect complementary log-log regression model with cataract status as interval-censored data, we estimated the effect of mets on the incidence of different types of cataract at different time-intervals. results: after taking into account the changes in mets (components) and controlling for possible confounders, mets was found to be associated with increased -year incidence of cortical cataract [hazard ratio (hr) . , % confidence interval (ci) . - . ] and psc (hr . , % ci . - . ). amongst the five components of the mets, high glucose and obesity predicted the -year incidence of cortical cataract and at -year, high glucose and low-hdl was associated with increased incidence of psc and cortical cataract, respectively. conclusions: changes in mets predicted the -year incidence of cortical cataract and psc. different mets components predicted the incidence of different sub-types of cataract at varying time-intervals. material and method: this study was a done on a sample of isfahan cohort study (ics) participants. subjects which met atpiii criteria, entered in our study. aobesity indices such as body mass index (bmi), waist circumference (wc), waist to hip ratio (whr) and waist to height ratio (whtr) measurements were done by trained nurses. serum lipids, fasting blood glucose, interleukin- (il- ) and interleukin- (il- ), adiponectin ghrelin, and crp were measured. the mann-whitney u-test was used for comparisons between the level of inflammatory markers in obese subjects with and without mets. then subjects with mets were selected and correlation between inflammation biomarkers and obesity indices correlation coefficients were obtained by pearson correlation test. results: wc and bmi were significantly higher in subjects with mets (p < . ). the median (iqr) of crp was significantly higher in subjects with mets (p < . ). the correlation between inflammatory markers and obesity indices was determined by nonparametric analysis. mets subjects had a significantly positive correlation between il and whtr (r = . , p = . ). no significant relationship found between il- , ghrelin, adiponectin and crp with, bmi, whtr and waist. significant negative correlation was observed for adiponectin and the waist (r = À . , p = . ). negative correlation between adiponectin with whr, whtr and bmi among subjects without mets (r = À . , r = À . and À . respectively). conclusion: present study indicate that the observed inflammatory concentrations cannot be explained by type of obesity. objective: the incretin effect is known to be decreased in type diabetes (t d). however, no study has directly measured the incretin effect in non-caucasian subjects. because asian patients with t d are characterized by decreased insulin secretion, this study set out to examine the incretin effect in korean subjects with normal glucose tolerance (ngt) or t d. research design and methods: we performed g ogtts and corresponding isoglycemic intravenous glucose infusion (iigi) studies in subjects with ngt (n = ) or t d (n = ). the incretin effect was calculated based on the incremental area under the curves (iaucs) of insulin, c-peptide, or insulin secretion rate (isr). the plasma levels of total glucagon-like peptide- (glp- ) and glucosedependent insulinotropic polypeptide (gip) were measured by elisa. results: the incretin effect was not different between the subjects with ngt and t d ( ae % vs. ae %, p = . by insulin; ae % vs. ae %, p = . by c-peptide; ae % vs. ae %, p = . by isr, respectively). however, the gastrointestinally mediated glucose disposal (gigd) was decreased in t d ( . ae . % vs. . ae . %, p < . ). the plasma levels of the total glp- and gip during the ogtts were comparable between the two groups. conclusions: in koreans, the secretion of glp- or gip during ogtts and the incretin effect were comparable between subjects with ngt and t d, whereas the gigd was significantly decreased in patients with t d. a.e. berezin , a.a. kremzer internal medicine, clinical pharmacology, state medical university, zaporozhye, ukraine the aim of this study was to evaluate the interrelation between circulating osteoprotegerin (opg) and coronary vasculature damage in type diabetes mellitus patients. methods: one hundred and twenty-six subjects with stable diabetes mellitus type with previously angiographic documented asymptomatic cad were enrolled to the study. vessel-wall and plaque geometrical and compositional parameters were measured on contrast-enhanced ct angiography. the volume of intramural calcium of > hu in major coronary vessels was measured in coronary segments with a highly standardized method. coronary artery calcification was quantified by calculating the agatston' score index and calcification mass measurement. opg plasma levels were measured with elisa. results: circulating opg level was increase in patients [ pg/ ml [ % confidence interval (ci) = - pg/ml] and was normal in subjects ( pg/ml; % ci = - pg/ml; p < . ). the relationship between coronary artery calcium by agatston' score index and percent atheroma volume (pav) was determined by linear regression. pav and remodeling index were significantly higher in patients with elevation of opg plasma level when compared with those who have normal opg [adjusted odds ratio (or) = . ( % ci = . - . ); p = . ]. there was significant correlation between agatston' score index and pav [r ( ) = . , p = . ]. in conclusion, we demonstrated that opg plasma level can associate with vessel-wall thickening, percent atheroma volume, and agatston' score index value in type diabetes mellitus patients with previously angiographic documented cad. along with the prevalence of diabetes continues to grow, the occurrence of microvascular chronic complications caused by diabetes has increasingly become a serious social problem. diabetic cardiomyopathy, a microvascular disease, results in chronic heart failure and causes a heavy economic burden. endoplasmic reticulum as an intracellular organelle, which occurs the stress leads to cell apoptosis. recent studies indicate that bis(maltolato)oxovanadium can alleviate the endoplasmic reticulum stress to protect cell function. in this study, stz ( mg/kg)-induced diabetic rats were divided into two groups, the diabetic control group, and diabetes + vanadium group; the normal group without diabetes were randomly divided into two groups, normal group and the normal + vanadium group. the bis(maltolato)oxovanadium significantly improve the endoplasmic reticulum stress in stz-induced diabetic rat heart cells and reduce the cardiac damage. in this study, bis(maltolato)oxovanadium can reduce the endoplasmic reticulum stress in diabetic myocardial cells delay the development of diabetic cardiomyopathy. it can be a new way to explain the mechanism in the function of bis(maltolato)oxovanadium. between mets and type diabetes families without diabetic family related. subjects and methodology: forty-three mets subjects with type diabetes parental ( st group), mets subjects without type diabetes parental ( nd group) and no mets subjects but with type diabetes parental ( rd group). this study was conducted over months at diabetologia department hospital. diabetes screening was achieved by oral glucose tolerance testing (ogtt). metabolic parameters were determined by spectrophotometry, insulin by radioimmunoassay. insulin sensitivity was also assessed by the homeostasis model assessment (homa) approach (glucose insulin/ . ). results: in the st and the nd groups there is a significant hyperinsulinemia and to a lesser extent in the rd group ( %, % and %, respectively). the homa model confirms an acute insulin resistance ( %, % and % increase respectively). hypertriglyceridemia was observed only in the nd group. hdl dyslipidaemia has been identified in women of the nd group (< . g/l). our study seems to confirm that type diabetes genetic predisposition is not the only factor, but also environmental factors with or without diabetes family. aims: to examine, the predictors of incident chronic kidney disease (ckd) in a community-based cohort of middle east population, during a mean follow-up of . years. methods: in a sample of non-ckd iranian adults ! years the estimated glomerular filtration rate (egfr) was calculated at baseline and at year intervals during three consecutive phases. the egfr < ml/min/ . m was defined as ckd. multivariate logistic regression analysis was used to determine the independent variables associated with incident ckd. results: the incidence density rates of ckd were . and . per , person-year, among women and men, respectively. female gender per se was associated with higher risk of ckd, compared with males. among women, age, egfr, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for ckd; however the intermediate degree of education and family history of diabetes decreased the risk by % (p < . ). among male subjects, independent predictors of developing ckd included aging and hypertension (with significantly higher risk than in women, p for interaction < . ), egfr, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of ckd about % which was marginally significant. in the iranian population, > % of individuals develops ckd each year. our findings confirmed that sex-specific risk predictors should be considered in primary prevention for incident ckd. introduction: obesity is a silent killer and a forerunner of many complications if persists long. various studies with animal model have identified the role of leptin, the hormone of adipose tissue; in obesity and its associated complications like diabetes and atherosclerosis inlater stages. the exact mechanism to know how leptin influences insulin action in body and thereby leading to diabetes or post diabetic atherosclerosis is still not completely evaluated. hypercholesterolemia was only found common to all these three states. aim and objectives: the present study, therefore, evaluated the role of obesity on the expression of ldlr receptor, insulin receptor and leptin receptor. method: receptor expression was done by immunohistochemistry/ western blot. the serum level of lipids were measured by enzyme based kit method. the serum level of insulin and leptin and its soluble receptor were measured by elisa based kit. the blot for insulin expression shows no chamge with body weight; the blot for leptin receptor shows decrease expression with weight gain and blot for ldlr shows decrease expression with weight gain. the serum levels of insulin and leptin are increased with weight gain but soluble receptor for leptin did not change significantly. even the obese group showed decrease tyrosine phosphorylation of insulin receptor. background: visfatin and apelin are two new adipokines that recently gained special interest in diabetes research. however, the relationship between them has not been elucidated and their role in coronary artery disease (cad) complication of diabetes has not been adequately studied. objective: this study was conducted to study the interplay between these two novel adipokines and to study their correlation with other inflammatory and biochemical parameters in type diabetic (t d) postmenopausal women with cad. the levels of visfatin, apelin and other parameters were measured in t d patients without cad, both nonobese and obese t d patients with cad, together with healthy nondiabetic control subjects. visfatin and apelin were measured by enzyme-linked immunoassay (elisa). results: visfatin was found to be significantly higher in the following groups: t d patients without cad, non-obese and obese t d patients with cad, ( . ae . , . ae . and . ae . ng/ml respectively) when compared to control group ( . ae . ng/ml) at p < . . apelin was found to be significantly lower in both non-obese and obese t d patients with cad ( . ae . and . ae . ng/ ml respectively) when compared to control group ( . ae . ng/ml) at p < . . furthermore, visfatin and apelin were found to be significantly associated with each other and with other biochemical parameters in both simple and multiple regression analyses. the current study provides evidence for the novel interplay between visfatin and apelin through the inflammatory milieu characteristic of t d and sheds light on their possible role in the pathogenesis of cad complication of t d. aim: the aim of this study was to investigate the relationship between hscrp, il- , and hcy levels and cardio metabolic risk factors in subjects with and without mets in a sample of tehranian population. in this cross-sectional study, individuals including men and women, aged ! years were selected randomly from among participants of tlgs. the sera of il- , hscrp and hcy were determined using elisa method. results: of the total subjects, aged mean . ae . year, mets was presented in ( . %) individuals. the levels of hscrp, hcy, and il- were higher in subjects with mets compared to normal group. a gradual significant increase just in the level of hscrp with increasing number of mets components was found after adjustment for sex and age. a strong linear augmentation in hscrp levels was observed as the number of mets components increase from to ! with median hscrp levels of . , . , and . (ng/ml) (p trend = À ). also, an increase of . in hscrp levels (ci %: . - . ; p = À ) was observed with an increase in each components of mets in linear regression analysis adjusted for age and sex. the best predictor for hscrp, il- , and hcy, in subjects with mets was hip, whtr, and height, respectively, compared with whtr and wrist which were the best predictors for hscrp and hcy levels in the subjects without mets. conclusion: hip and whtr are significant predictors of the hscrp and il- elevation associated to mets, respectively. methods: in a nested case-control study, conducted on a group selected from participants of the tehran lipid and glucose study, those cases with new diagnosed type diabetes during the . year follow-up ( subjects) were matched to controls for age, sex, body mass index andseason of entrance to study. multivariate conditional logistic regression analysis was used tocalculate the odds ratio (or) with % confidence interval of type diabetes for vitamin dcategories, vs. the first quartile ( . ng/ml) as reference. results: the unadjusted ors of type diabetes were . ( . - . ), . ( . - . ) for the second and third tertiles, respectively. after adjustment for family history of diabetes, systolicblood pressure, triglycerides to high density lipoprotein cholesterol ratio, and fasting plasmaglucose, the corresponding ors were . ( . - . ) and . ( . - . ) for second and third tertiles respectively. multivariate cubic spline modeling analysis indicated that ng/ml hydroxyvitamin d levels was the optimal cut point for distinguishing those who were at risk ofdeveloping diabetes and those who were not. also addition of vitamin d to multivariate model, improved the net reclassification by cut-point based nri of %. discussion: in a prospective cohort study, we demonstrated a nonlinear independent associationof vitamin d with incident diabetes, with prominent increase in risk at a cut-off < ng/ml. research department-ayush projects, svyasa university, bangalore, india type diabetes mellitus (t dm), the seventh leading cause of death, is a biggest challenge for mankind. despite of fascinating advances in pharmaco-therapeutic agents, the prevalence of t dm is growing every year. complementary and alternative medicine (cam) as classified by national centre of cam have documented various positive results of t dm. whole ancient medical systems like ayurveda, siddha, and tcm etc use natural herbs either as a single drug therapy or in the form of formulations, depending upon principles of respective medical system. studies done on various herbs and mind body intervention like, yoga, acupuncture etc are found to be beneficial for t dm. this resulted, large number of physicians either referring to or practicing some of the more prominent and well known forms of cam. the concepts proposed and used by these cam systems (that are kept alive by cam practitioners for thousands of years) appear very mysterious to the present day biomedical practitioners. these models of therapies seem to have evolved through several phases of internal research just like the present day drug trials that go through four phases of intensive statistical evaluation. it appears that today's scientists need to follow the footsteps of research used by the ancient seers of tcm, ayurveda, siddha, yoga or homeopathy to unravel these mysterious theories. this review talks about generating evidence not only for the efficacy of these holistic systems but also in carrying out systematic research by biomedical scientist who have the knowledge of both the western and eastern sciences. background: the epidemic of obesity, over the last two decades, in the middle and high income countries is associated with marked rise in the incidence of metabolic syndrome. objective: to measure the prevalence of metabolic syndrome (ms) and determine its association with ratio of omega- /omega- fatty acids in the diet. design and methods: cross-sectional surveys were conducted in urban streets in the city of moradabad, india. randomly selected subjects with ms aged years and above were evaluated and graded according to omega- /omega- ratio in the diet. physical examination, sphygmomanometer, questionnaire and blood tests were done. results: the overall prevalence of ms was . % (n = ) without any gender difference. the prevalence of ms, type diabetes, cad and hypertension showed a higher rate, in relation to omega- /omega- ratio in the diet. subgroup analysis showed that subjects eating low omega- /omega- ratio (< . ) diets had significantly lower prevalence of ms, and related components compared to higher ratio diets, among both sexes. multivariate logistic regression analysis after adjustment of age showed, that hypertriglyceridemia (odds ratio . in men, . in women) was strongly (p < . ) associated with ms. hypertension, hdl-c, and central obesity were weakly associated with ms in both sexes. hypercholesterolemia was weakly associated with ms only in women. conclusion: ms has become a public health problem in india. higher w- /w- ratio is a major risk factor of ms and cad. it is possible that a low w- /w- ratio in the diet (< . ) may be protective against ms. objective: investigate the differences in clinical and laboratory features (including some adipocytokines) among hyperglycemic patients with or without cad. methods: five hundred and sixty-one consecutive hyperglycemic subjects undergoing coronary angiography. hyperglycemia [diabetes mellitus (dm)/pre-diabetes (pd)] previously known dm or diagnosed at the moment of recruitment by an hba c (hplc) levels-! . - . %-pd, ! . %-dm (ada criteria). cad defined by any lesion ! % on angiography. results: . % were men. age was . ae . (mean ae sd), cad was detected in . % of individuals. patients with cad were older ( ae vs. ae years, p = . ), more often male ( % vs. %, p = . ). additionally, they showed a worse metabolic profile, with higher hba c ( . ae . % vs. . ae . %, p = . ), fasting plasma glucose ( ae vs. ae mg/dl, p = . ), triglyceride [ ( - mg/dl) vs. ( - mg/dl), (p = . )] and plasma visfatin/nampt levels [( . ( . - . ng/ml) vs. . ( . - . ng/ml), (p = . ), median/interquartile range], and lower hdl-cholesterol levels ( ae vs. ae mg/dl, p < . ), even after correction for statin use (except for hdl and visfatin/nampt). diabetic patients with cad had greater diabetes duration than diabetic individuals without cad: . ( . - ) vs. . ( - ) years, median and interquartile range, (p = . ). systolic and diastolic blood pressure, homa%-s, homa-ir, total and high-molecular weight adiponectin levels were similar in both groups. conclusions: patients with hyperglycemia and cad have a worse glycemic and lipid profile and higher visfatin/nampt levels as compared to those without cad. one hundred and sixty-nine patients (p) with the mets were studied to find out the incidence of cardiovascular events, especially myocardial infarction and strokes. the mean age was years. fifty-five percent were males and females. the mean body mass index was kg/m . the mean fasting blood sugar was mg/dl. ninety-seven percent were diabetic type ii and % diabetic type i and the lipid profile was normal. the studied population showed a higher incidence of atrial fibrillation, when compared with a comparison group of diabetics ( % vs. . %) p < . . no ventricular tachycardia was observed. the mets group showed a subnormal ejection fraction ( ae %) when compared with a comparison group ( ae %) p < . . no myocardial infarctions or strokes were detected. coronary angiography was done in % of the (p) all were negative except one. the lower ejection fraction was explained on basis of diabetic cardiomyopathy. the genetics profile of the puertorrican, a hispanic population, is more of an european, indian and african. probably, this produces a culture less sensitive to the atherosclerotic factors, producing a less aggressive mets syndromeless myocardial infarcts or strokes. this suggest that genetics and culture is an important aspect of the expression of mets, especially in the hispanic world. objectives: controversy surrounds the annual progression from prediabetes (impaired glucose regulation) to type diabetes. current uk statistics suggest a % progression rate. our aim was to assess subjects in our locality at high-risk of progression from pre-diabetes to type diabetes within a month period. this will establish whether current recommendations for follow-up of high-risk subjects successfully identify those with pre-diabetes. methods: analysis was performed on data from high-risk subjects who underwent ogtt with baseline clinical and biochemical measurements. the ogtt and biochemical measures were repeated at months. results: of the subjects, ( . %) developed diabetes within the month period, significantly higher than the estimated annual progression rate (p . ). as expected, baseline fasting plasma glucose was higher for subjects that progressed to diabetes (diabetes vs. no diabetes: . ae . vs. . ae . mmol/l; p . ), as was h post-prandial plasma glucose (diabetes vs. no diabetes: . ae . vs. . ae . mmol/l; p . ). additionally, baseline hba c was higher for those that developed diabetes [diabetes vs. no diabetes: . ( . - . ) vs. . ( . - . ) %; p = . ]. interestingly, both sbp and dbp were significantly higher at baseline in those that developed diabetes (sbp: ae . vs. ae . mm hg; p = . ) (dbp: ae . vs. ae . mm hg; p = . ). conclusions: within this cohort, progression to type diabetes was almost twice the current estimated annual rate. fasting, h-glucose, hba c and blood pressure were associated with progression from prediabetes to type diabetes over months. methods: tissue lysates from visceral fat samples of subjects undergoing abdominal surgery (predominantly bariatric and routine non-acute for non-malignant conditions) were collected from subjects categorised as l ( ), o ( ) or odm ( ). a commercially available comet assay (cell biolabs, inc) was used to assess cellular dna damage using a single cell gel electrophoresis method. additionally, results indicate a greater percentage of dna migration from the comet "head" to its "tail" within odm samples (l vs. o vs. odm: . vs. . vs. . %; p = . ). in conclusion, results suggest that visceral fat from obese subjects with type diabetes are subject to higher levels of oxidative burden resulting in a higher proportion of damaged dna. community medicine, faculty of medicine, kuwait university, jabriya, kuwait background: the prevalence of overweight and obesity are high in kuwait. metabolic syndrome is associated with both. it is expected to find the syndrome to higher than in other countries. objective: to assess the prevalence of ms using two different diagnostic criteria, the international diabetes federation (idf) and the national cholesterol education program-third adult treatment panel modified for age (ncep-atp iii). study design: a multi-stage random sample study. methods: the analysis of data for this study was based on a sample of male kuwaiti adolescents, - years of age selected from intermediate and high schools. anthropometric measurements and biochemical tests on blood samples were carried out. the idf criterion requires waist circumference (wc) plus two of the following criteria: triglycerides (tg), high density lipoprotein (hdl), fasting blood sugar (fbs) and blood pressure (pb). the atp iii criterion requires three of the above parameters. the parameters mentioned must show increase in their values except for hdl which must show decrease in either criterion used. results: each of the two criterion revealed that the prevalence of ms was . % and . %, using the idf and the atp iii criteria, respectively. hdl decreased in each of the two diagnostic criteria and the other four parameters increased, satisfying the diagnostic requirements of either criterion. conclusions: significant implications may be drawn from these results, especially when it comes to being at risk of type diabetes (t d) and cardiovascular disease (cvd). m. saghebjoo , j. shabanpour omali , r. fathi university of birjand, birjand, mazandaran university, babolsar, iran background and aims: resistance training has been shown to be beneficial in older adults. however, very little data exist on the effects of resistance training in older diabetics. chemerin is a adipokine that has been shown to induce insulin resistance in skeletal muscles. here we investigate the role of weeks of progressive resistance training (prt) on plasma chemerin levels in older men. methods: a total of sedentary men with type diabetes, aged between and years, were randomized to the weeks supervised prt (n = ) and control (n = ) groups. chemerin, insulin, glycosylated hemoglobin (hba c), and fasting blood glucose (fbg) were measured before and h after the training period. results: plasma chemerin levels decreased significantly (p = . ) in the , and exhibited significant reductions in plasma insulin (p = . ) and fbg (p = . ). fbg decreased by . % in prt group. conclusion: reduced plasma chemerin concentration may contribute to improved insulin sensitivity. these results recognize that increased intensity of exercise may produce greater benefits, but may not be appropriate for some individuals. some studies have demonstrated the presence of metabolic syndrome in children and adolescents, but few have investigated this syndrome in brazilian children. the aim of this study was to investigate the prevalence of metabolic syndrome in children and its association with gender and nutritional status. this transversal epidemiological study involved children of both genders between . and . years old. there were collected sociodemographic, anthropometric, metabolic and hemodynamic data. the nutritional status was obtained according to the body mass index. to diagnose metabolic syndrome was used the criteria proposed by the national cholesterol education program′ s adult treatment panel iii adjusted for age. there were used two separate proposals (cook et al., ; ferranti et al., ) . the prevalence of metabolic syndrome ranged from . % to . %, depending on the criterion. the nutritional status showed . %, . % and . % of children with normal weight, overweight and obesity, respectively. significant association was observed between the metabolic syndrome and nutritional status, but not in relation to gender. metabolic syndrome was present in different nutritional status of children, especially those with excess body weight, thus indicating the importance of early diagnosis and the adoption of primary prevention measures already in pediatric patients. introduction: ifg (fpg . - . mmol/l) is a risk-factor for developing type diabetes and cardiovascular disease. we quantified changes in ifg prevalence (post-hoc analysis) from a double-blind, placebo-controlled trial investigating the effects of liraglutide . mg on maintenance of diet-induced weight loss (primary endpoint). methods: overweight/obese adults ( ! years, bmi ! or ! kg/m with comorbidities) who lost ! % weight after - week run-in with low-calorie diet ( - kcal/day) and exercise were randomised to once-daily subcutaneous liraglutide (n = ) or placebo (n = ), plus kcal/day deficit diet and exercise. the full-analysis-set comprised of randomised individuals [age . ae . years, bmi . ae . kg/m (mean ae sd)]. during run-in, participants lost . ae . kg weight and ifg prevalence decreased from % ( / ) to % ( / ). at week , liraglutide-treated participants lost an additional . kg from randomisation (table ) , whereas placebo-treated participants lost no additional weight [treatment-difference À . kg ( %ci À . ; À . ); p < . ]. moreover, the proportion of participants with ifg at week was lower for liraglutide ( . %) than placebo ( . %; odds-ratio . [ . ; . ]; p < . ). at week , after weeks off treatment, the liraglutide group regained~ kg lost weight and ifg prevalence increased. mean weight loss remained greater for liraglutide vs. placebo [treatment-difference À . kg (À . ; À . ); p < . ] but ifg prevalence did not differ (odds-ratio . [ . ; . ]; p = . ). conclusion: liraglutide decreases ifg prevalence in overweight/obese individuals who have already lost weight by diet and exercise, potentially due to additional weight loss and weight-loss independent mechanisms. objective: we wanted to explore the association between polymorphisms of irs (rs ), tcf l (rs and rs ), adrb (rs ), pparg (rs ), and hhex (rs ) genes with insulin resistance, lipid profile and atherogenic risk in mets patients from the mexican social security institute. methodology and results: four hundred and thirty-one mets patients and controls were selected. the association between the snps and the atherogenic index was evaluated by multiple linear regression and multinomial logistic regression models. adrb c/g were associated with an increase in ldl-c levels (β = . , % ci = . , . p = . ), the hhex t/c variant were statistically associated with an increase in total cholesterol levels (β = . , % ci = . , . p = . ), and with an increase in ldl-c levels (β = . , % ci = . , . p = . ). the adrb gene showed a statistically significant association with high-risk atherogenic index, (or = . , ic % . - . ; p = . ) for the arg/gly variant and for the dominant model (or = . , ic % . - . ; p = . ). conclusions: the arg gly polymorphism of the adrb gene may be a good biological marker to predict the risk of developing cardiovascular diseases given a high-risk atherogenic index. aims: describe the knowledge of major risk factors for type diabetes held by primary health care (phc) nurses involved in the community management of diabetes. methods: random sample ( %) of phc nurses in auckland. information was collected from postal and telephone questionnaires, on education, experience, knowledge and diabetes management practice. results: responses were received from phc nurses ( % response) comprising practice nurses (pns), district or homecare nurses (dns) and specialist nurses (sns). most nurses ( %) were able to identify excess body weight as a major risk factor for type diabetes. only % of sns and a third of pns and dns identified lack of physical activity, and fewer than % of sns and pns, and only % of dns identified hypertension as risk factors. even fewer respondents were able to identify individual lipidsalthough significantly more sns identified elevated triglycerides ( %, p = . ) and reduced high-density-lipoprotein cholesterol ( %, p = . ) as major risk factors compared with only - % of pns and no dns. risk factors for diabetes-related complicationsapart from hyperglycaemia identified by %were not well identified, particularly smoking ( %), hypertension ( %), triglycerides ( %) and reduced high-density-lipoprotein cholesterol ( %). in general, phc nurses had a good knowledge of overweight as a risk factor for type diabetes and hyperglycaemia as a risk factor for diabetes-related complications, but poor knowledge of cardiovascular risk factors, particularly smoking. yoga and life sciences, swami vivekanand yoga anosandhana samsthana (s-vyasa university), bangalore, india metabolic syndrome is clustering of different metabolic abnormalities which encompass central obesity, insulin resistance and hypertension. it is characterized by an overdrive of the sympathetic nervous system, increased oxidative stress, elevated pro-inflammatory enzymes, and impaired circadian cycle. lack of physical exercise, improper eating habits, and psychological stress are also common contributing factors to this condition. thus, life style change which includes adequate exercise, proper diet and stress management are the keys in prevention control and treatment of metabolic syndrome. yoga, one of the ancient sciences on earth, is known to bring balance at all aspects of human existence. its different components like asana (physical postures), pranayama (breathing techniques), meditation and relaxation techniques (yoga nidra) etc have been proven to influence body and the mind towards balance and equanimity. recent scientific studies on yoga have proven its safety and efficacy in the management of many metabolic disorders which includes diabetes mellitus, obesity, hypertension and atherosclerosis. yoga therapy has also caused reduction in the pro-inflammatory cytokines in such conditions. yoga reduces sympathetic tone as well as oxidative stress; it helps in reducing insulin resistance by enhancing secretion of melatonin and hepatic insulin sensitizing substance through bringing the parasympathetic dominancy. thus, we propose that yoga has an important role in prevention and treatment of metabolic syndrome as a complementary or as an alternative to conventional line of treatment. s. debnath , s. addya medical laboratory technology, women's polytechnic, medical officer, government of tripura health services, agartala, india introduction: saliva is an excellent biological matrix that offers several opportunities for scientific inference of diagnostic, toxicological and in forensic importance. numerous salivary metabolites proffer great potential in clinical and epidemiological research. sample collection is non invasive and analysis require simple modifications. establishing good correlates is the need. objective: our objective was to study the association between anthropometric measures (ams) with salivary metabolites in a subsample (n = ) of college women in suburban north east india. method: saliva and blood samples were photometrically analyzed for glucose, protein and urea. ams as bmi and waist circumference (wc) were measured in female students of menstruating age ( - years) following who guidelines. ams were correlated (pearson's correlation, ′r′) to salivary biochemistry. results are reported with intra assay coefficient of variation (cv < % all assays) in the text. ′ four day diet dairy′ was maintained over the period. results: salivary biochemistry found to be significantly correlated to ams in the studied subsample. salivary protein was negatively correlated (′r′ = À . ) with bmi and with wc (′r′ = À . ) whereas salivary glucose (′r′ = . with bmi and ′r′ = . with wc) and urea (′r′ = . with bmi and ′r′ = . with wc) had positive correlation. all assays performed in triplicates .we observed very good repeatability of results. medicine -cardiology, massachusetts general hospital, boston, ma, usa introduction: obesity is an independent risk factor for cardiovascular disease. supine bike stress echocardiography is suggested to be of particular utility for evaluating for coronary artery disease (cad) in obese individuals given the lack of mechanical impact with this modality. database for all recumbent bicycle stress echocardiography examinations performed between january , and july , . all tests performed to evaluate for cad were reviewed. two groups were formedpatients achieving ! % of maximum predicted heart rate (mphr) and those achieving < % mphr. medical records of these patients were then reviewed. comparisons between groups were made using unpaired t-tests and correlations between patient characteristics and hr were assessed using pearson's correlation. results: four hundred and sixty tests were done to evaluate for cad. one hundred and eighty-one ( . %) patients failed to reach % mphr during testing. forty-three percent of patients failing to achieve % mphr were obese (bmi > ) vs. % of all patients referred for stress testing. image quality among obese patients was not notably worse compared to leaner patients. those failing to achieve % mphr had a significantly higher bmi ( . vs. . ; p = . ) than those with adequate hr response. bmi exhibited a negative correlation with percent mphr (r = À . , p = . ). conclusion: obesity is associated with failure to achieve ! % mphr during supine bike stress echocardiography done to evaluate for cad. use of adjunctive pharmacologic agents should be considered when evaluating an obese patient for cad with stress echocardiography. ( ): - ), though the extent to which body weight may act as a confounder or as mediator in this relationship is uncertain. the aim of this study was to analyze whether the association between crf and mets risk is mediated by body mass index (bmi). methods: cross-sectional study including schoolchildren, - years old from the province of cuenca, spain. we measured height, weight and crf ( -m shuttle run test). a validated mets index (diabetes care ; : - ) was estimated by summing standardized z scores of waist circumference, triglyceride-to-hdl-c ratio (tg/hdl-c), mean arterial pressure (map), and fasting insulin. to test whether the association between crf and mets index and its components was mediated by bmi, linear regressions models were estimated according to baron and kenny procedures for mediation analysis (j pers soc psychol. ; : - ) . results: in girls, bmi acts as a fully mediator for the relationship between crf with mets index and all its components, except for tg/ hdl-c ratio. in boys, bmi acts as a fully mediator for the relationship of crf with tg/hdl-c ratio and map; and partial mediator for the relationship between crf with mets index and the rest of components. the obesity mediates the association between crf and mets in schoolchildren. good levels of crf are associated with lower mets risk, but only when accompanied by weight reduction. pre intervention measurement was applied. no statistical differences were found for prediabetes knowledge, physical activity, eating habits, bmi, weight, waist circumference and clinical parameters (glucose, triglycerides and total cholesterol) between both groups in basal measurement. the control group received the usual care from health centers. in the study group, the intervention was developed during months per patient (received usual care plus remote care model′s components). the rct will end at january , and the final results will be presented. chronic conditions. this study compares the prevalence of the metabolic syndrome (mets) between genders in the workplace. methods: as part of the established "prosiect sir gâr" initiative in south wales, uk, female and male employees from either the local steel works or local health board were screened and their data analysed. anthropometric data, blood pressure, self-reported physical activity (gppaq) and smoking status were all recorded. in addition, blood samples were obtained and analysed for high-densitylipoprotein cholesterol (hdl-c). presence of the mets was determined based on the following idf criteria: central obesity (females waist circumference: ! cm; males waist circumference: ! cm), reduced hdl-c levels (females: < . mmol/l; males: < . mmol/l) and either systolic ( ! mmhg) or diastolic ( ! mmhg) hypertension. results: a higher proportion of males were diagnosed with mets than females ( . % vs. . %; p < . ) despite the males being more physically "active" or "moderately active" ( . % vs. . %; p < . ). rates of central obesity and systolic hypertension were comparable between genders (p > . ), however prevalence of diastolic hypertension, reduced hdl-c levels, current smokers and individuals either overweight or obese were higher in the male cohort (p < . ). conclusion: despite being more physically active, males were more susceptible to the mets than females, likely due to a higher percentage of smokers and either overweight or obese. conclusions: the addition of glp analogues to insulin therapy seemed to be superior to the enhancement of insulin therapy regarding to weight loss, decreases of hba c, hypoglycemic episodes and requirements of insulin. it was also observed a significant improvement in insulin sensitivity and in beta cell function. background and aims: type diabetes is often associated with nonalcoholic fatty liver disease (nafld). patients with nafld may be at greater risk for cvd than those without. the relationship between nafld and metabolic syndrome (ms) is very well recognized. the aim: to determine the association of nafld and cvd between type diabetic patients with and without ms. materials and methods: one hundred and thirty type diabetic patients (m: , f: , mean age . + . ), were studied. all subjects were assessed for diabetes duration, the obesity degree, cv risk factors, hba c, c reactive protein and lipid profile. nafld was assessed by patient history and ultrasound. ms was defined based on ncep-atp criteria. the previous and current cvd (myocardial infarction, angina or revascularization) was assessed. we categorized four groups: ms (À) and nafld(+), ms(À) and nafld(À), ms(+) and nafld(+), ms(+) and nafld(À). results: the prevalence of cvd in type diabetic patients with nafld was higher than in those without nafld ( . % vs. . %). the prevalence of chd in type diabetic patients with ms was higher than in those without ( . % vs. . %). the risk of chd in patients with ms was significantly increased by the presence of nafld ( . % vs. . %). in type diabetic patients with ms(+) and nafld(+) the number of components of ms, bmi, and systolic bp were positively associated with chd. conclusions: what this study suggests to us is that the presence of nafld increases the risk of cvd in type diabetic patients with ms. and to determine associations between the levels of fasting blood sugar and its comorbid conditions. this is a retrospective study and uses chart review in the outpatient section of the family medicine clinic. it also uses percentages, means and its standard deviations, and chi square to detect associations. there were patients with impaired fasting glucose aged between and years old (mean age . ae ) and all were of filipino ethnicity. there were more females than males. the mean body mass index was . ae . kg/ m and the mean fasting blood sugar (fbs) was . ae . mg/dl. there was no association between the fbs level and obesity (p > . ) and hypertension (p > . ) in this study. however, fbs > mg/dl was associated with the presence of family history of diabetes in this population (p < . ). it seemed that ifg can occur to young, nonobese patients with family history of diabetes. this study recommends that screening for ifg among filipinos should be done to all patients with a strong family history of diabetes regardless of age, gender, bmi status or presence of hypertension. h. hasan, v.l. raigangar, a.r. abdullah methods: a cross-sectional study of young females (mean age . ae . years. leptin, insulin, high sensitivity c-reactive protein (hs-crp), c-peptide, ua, bg, hdl-cholesterol and triglycerides were estimated from a fasting blood sample. anthropometric parameters (wc, height and weight) and bp were measured. homa-insulin resistance was also calculated. results: mean wc of the studied population was . ae . cm, % (n = ) had wc > cm. for the subjects, all studied parameters were within normal limits except leptin which was high; . ae . ng/ml. ua showed highly significant positive correlation with wc (r = . , p < . ), significant positive correlations with cpeptide, hs-crp and leptin with (r = . , p = . ), (r = . , p = . ) and (r = . , p = . ) respectively. ua demonstrated significant negative correlation with hdl only (r = À . , p = . ). multiple linear regression revealed that wc was the only significant predictor of ua levels (b = . , p = . , ci %: . - . ). conclusion: this study stresses the importance of ua levels in cvd particularly due to its strong association with wc, the main indicator of abdominal obesity in mets that is often missed. ua may hence be considered a valuable biomarker for early prediction/detection of mets in young females. background: adipocyte-secreted cytokines are associated with inflammation and metabolic disturbances but it is unclear how their snps interfere on the response to lifestyle interventions. we assessed associations of selected snps with the changes induced by interventions. methods: this -month intervention on diet and physical activity included brazilians at cardiometabolic risk (prediabetes or metabolic syndrome without diabetes). changes in clinical variables were analyzed according to the presence of the tnfa- g/a, il- - g/c and adipoq t/g snps; individuals with at least one variant allele were grouped and compared with the reference genotype. afterwards, individuals carrying simultaneously the genotypes associated with no glycemic response were grouped and compared to the remainder sample. results: the entire sample ( . ae . years) had lower energy intake, higher physical activity, and improved anthropometric and metabolic variables after intervention. carriers of the tnfa variant allele but not the reference group decreased plasma glucose. il- and adipoq variant allele carriers had worse glucose, lipid and inflammatory responses. grouping the subset of carriers of tnfa- g + il - c + adipoq g, they showed a significant increase in mean fasting glucose after intervention. this increment differ significantly from the behavior of the remainder sample (+ . % vs. À . %, p = . ). the tnfa- g/a but not the adipoq t/g and il- - g/c may predispose a better response of glucose metabolism to a lifestyle intervention. the combination of three worst genotypes can maximize the adverse effect on glucose metabolism in at-risk brazilians. further studies are needed to direct lifestyle interventions to specific subgroups of individuals. obesity is a metabolic disorder, which is associated with an increased risk of various conditions, including sexual dysfunction. objective: to investigate anthropometric indicators of body fat in postmenopausal women influencing their quality of life. material and methods: the study was performed at the scientific and clinical study of endocrinology, uzbekistan public health ministry. a total of women (mean age of years) was examined. bmi, waist circumference and waist to hip ratio were obtained for anthropometric evaluation. lipid specters, glycemia and insulin were the parameters to evaluate. we have used a menopause quality of life questionnaire and female sexual function index questionnaire (fsfi). the quality of life of the obese and overweight patients was compared by age, education, marriage and matched with healthy normal weight controls. results: overweight and obesity were observed in of women. values of wc > cm were above normal levels in %, . %, respectively, and hdl was normal in . %. homa -ir was measured in . % of the women. women with overweight and obesity had worse general health-related quality of menopausal symptoms, life and psychological and sexuality scores than athletic and lean women (bmi ! ). in fsfi it was significant differences in such as scales as desire and orgasmic disorders in women with metabolic syndrome (ms) in comparison with the controls (p < . ). aim: to determinate groups of high cardiovascular risk and start early hypolipidemic therapy due to genetic polymorphism of lipoproteidlipaseone of the main enzymes of lipid metabolism in metabolic syndrome and nafld patients, treating with combined therapy of statins and ursodeoxycholic acid (udca). background: health staff receive more health messages and information in working hours than others. moreover, they are supposed to be healthy models for the community. we conducted a screening of metabolic syndrome on shahid beheshti university health department staff (who are responsible for health affairs of more than million people in tehran province, iran) to assess their health level. we invited all of the health staff for screening on "the world heart day". weight, height, waist circumference, systolic and diastolic blood pressure were measured and a fasting blood sample was taken for lipid and glucose level testing. results: fifty percent of the staff ( person) participated in the screening. the mean age was . ae . years. only % were in normal weight range. overweight, obesity class and class rates were %, . % and . %, respectively. . % of all and . % of normal bmi cases had a high waist circumference. metabolic syndrome was identified in . % of men and . % of women. high blood pressure was detected in . % of the cases. in . % of all and . % of overweight or obese cases fasting blood glucose was elevated. these rates for blood total cholesterol level were . % and . %, for triglyceride were . % and . %, and for ldl were . % and . %, respectively. conclusions: contrary to our expectations, a high rate of metabolic syndrome was identified in this group. it seems that interventional programs targeting nutritional habits and physical activity of the staff are needed along with routine educational programs. introduction: physiologically, brain natriuretic peptides (bnp) and lipolysis are closely linked. obesity is been identified as a major risk factor for the development of cardiovascular diseases (cvd) and has been reported to have an impact on bnp in apparently healthy subjects but also in cvd patients. thus, we speculate that bnp could play an important role in lipid metabolism and may affect the pathophysiology of obesity in cvd patients. methods: serum samples were obtained from cvd elderly patients distributed in two groups: i-non-obese and ii-obese. the plasma mature form of brain natriuretic peptide (nt-probnp) was measured by a sandwich enzyme immunoassay with spectrophotometric detection at nm. conclusion: overall, these data demonstrates that obesity is an important and independent determinant of bnp expression in patients with cvd. inverse relationship between bnp and body mass index may suggest "beneficial" effects of obesity, but clearly lower levels did not confer a more favourable prognosis. the precise mechanisms linking obesity to cvd remain unsolved and may be due either to release attenuation or increases in clearance receptors. these effects should be taken into account for appropriate bnp reference values, so lower cut-points should be used for obese patients and a higher cutpoint for lean patients to increase specificity. v. mladenovic , a. djukic , s. djukic , n. arsenijevic , s. zivancevic simonovic aim: the aim of this study was to investigate dynamic of changes of oxidative stress during acute myocardial infarction depending on development phases of metabolic syndrome x. method: the research included patients; inclusion criteria were diagnosed metabolic syndrome and acute myocardial infarction. according to the movements of glycemia and insulinemia all patients were divided in four development phases of metabolic syndrome x. to evaluate oxidative status we determinated: lipid peroxids (malonyldialdehide), total antioxidative status, as well as oxidative stress coefficient. results: during hospitalisation in patients with acute myocardial infarction concentration of lipid peroxids increased, with maximum in the day th of hospitalisation, mostly in hyperinsulinemic phases of metabolic syndrome. at the st day of myocardial infarction total antioxidant status increased, and decreased during next days. these changes are independent on the phase of metabolic sindrome x. as result of inverse dynamic changes of these parametars, during period of exam came to progressive increase of oxidative stress coefficient, particularly in patients in hyperinsulinemic phase of metabolic syndrome x. conclusion: during first days after acute myocardial infarction lipid peroxids concentration progressively increased, with decrease of total antioxidant status, that results in increase of oxidative stress. these changes are most distinctive in patients with hyperinsulinemic phases of metabolic syndrome x. introduction: glp- (exenatide -lilly) is a good therapy for overweight or obese type diabetic patients, but bid administration might not be effective over h. aim: we intended to evaluate h effectivness of this drug in our outpatients using continuous glucose monitoring (gcm-medtronic). methods: we asked our outpatients to undergo a continuing glucose monitoring for days. twelve of them accepted [ f and mol/l, median age (range - ), median disease lenght years (range - )] and signed an informed consense; they had stable metabolic control with hba c < mmol/mol and had been on therapy with exenatide for months at least. results: glycemic profile demonstrates that no patient had experimented prolonged hypoglycemia and all subjects, expept for one, had mainteined a long period of euglycemia in range - mg/ dl during the blood glucose monitoring. conclusions: it′s our opinion that these data demonstrate exenatide can be surely used in type patients to obtain a good and stable metabolic control during all h inspite of the bid somministration and, moreover, the age or the disease lenght are not to be considered a contraindication to its use. several parameters of vascular function and structure have a predictive value for cardiovascular morbidity-mortality and for the presence of associated target organ damage in diabetic and hypertensive patients. superoxide dismutase (sod) is an intracellular antioxidant defense mechanism, which catalyses the dismutation of superoxide radical into h o and oxygen, and it is easily detectable in human plasma; oxidative stress is associated with cardiac and vascular defects leading to hypertension and atherosclerosis and with diabetic cardiomyopathy. on the other hand, osteoprotegerin (opg) is an indicator of diabetes-associated vascular pathologies as hypertension, endothelial dysfunction and cardiovascular risk. we have assessed the relationship between serum levels of sod, opg and parameters of vascular function and structure as well as cardiovascular risk in type diabetic patients with and without hypertension. there are negative correlations between sod and endothelial dysfunction (evaluated by pressure wave velocity, peripheral and central augmentation index and ambulatory arterial stiffness index), pulse pressure, diastolic and systolic night/day ratio, serum opg and plasma hdl-cholesterol, as well as positive correlations between sod and plasma uric acid, liver enzymes got, gpt and ggt, triglycerides and haemoglobin. on the other hand, serum opg is correlated to endothelial dysfunction, intima media thickness, pulse pressure, systolic night/day ratio and d′agostino cardiovascular risk index. our study shows that both sod and osteoprotegerin plasma levels are indicators of cardiovascular events and target organ damage associated with diabetes and hypertension. objective: we investigated the future coronary artery disease (cad) event rate in diabetic patients with and without chest pain in a prospective cohort study performed in a korean population. we also investigated the impact of chest pain on cad risk according to the presence or absence of diabetes mellitus. research design and methods: the ansung-ansan cohort was established for a prospective large-scale community-based epidemiologic study to investigate chronic diseases in korea. the data from a baseline survey performed from to and two subsequent prospective biennial surveys were analyzed. results: among subjects ( men and women) without a history of cad, . % and . % of non-diabetic and diabetic subjects, respectively, reported newly developed cad events during years of follow-up. diabetic patients had a significantly higher risk of future cad events (age-and sex-adjusted odds ratio, . ; % confidence interval, . - . ; p = . ). although the presence of chest pain at baseline was also significantly associated with an increased risk of cad of more than -fold in both non-diabetic and diabetic subjects (p < . ), the hazard ratio for cvd event in asymptomatic diabetic patients compared to non-diabetic subjects with chest pain was not significantly different from . (hazard ratio, . ; % confidence interval, . - . ). conclusions: diabetes and the presence of chest pain are independently and significantly associated with future cad event risk. asymptomatic subjects with diabetes have a comparable risk of cad events to non-diabetic subjects presenting chest pain. aim: the aim of the study was to select and analyze patients with diabetes mellitus and acute stemi or nstemi myocardial infarction from all patients hospitalized in cardiology department in . results: more patients with nstemi underwent pci in the history than patients with stemi (n = , . % vs. n = , . %); p = . and more pci and cabg (n = ; . % vs. n = ; %); p = . . concentrations of cpk (nstemi vs. stemi) (u/l) ( ae vs. ae ) p < . , ckmb (u/l) ( ae vs. ae ), p < . , glucose on admission (mg/dl) ( ae vs. ae ), p < . . patients with nstemi had less critical changes in the left anterior descending artery (lad) ( . % vs. . %); p = . , less bare metal stents (bms) implanted to the lad ( . % vs. . %one stent), and ( % vs. . %two or more stents), p = . . management of this patients shows figure . patients with stemi require more intensive treatment of more advanced concomitant metabolic disturbances. revascularization should by performed urgently because of higher death rate. during qualification for invasive diagnostic and treatment (pci and/or cabg), not only the risk of death and cardiovascular events should be taken into account, but also a history of revascularization modalities (pci and cabg). methods: a total of diabetic patients both sexes aged . ae . years were studied. the levels of total cholesterol (tc), triglycerides (tg), hdl-cholesterol (hdl-c), ldl-cholesterol (ldl-c), vldl-cholesterol (vldl-c), hba c and renal function tests were assessed. patients were classified as normoalbuminuric (albumin excretion rate < mg/ h, n = ), microalbuminuric (albumin excretion rate - mg/ h, n = ) and proteinuric (albumin excretion rate > mg/ h, n = ). results: the duration of diabetes was . ae . years. the level of tc was significantly highest in proteinuric ( . ae . mmol/l), followed by microalbuminuric ( . ae . mmol/l) and followed by normoalbuminuric ( . ae . mmol/l), (p = . , p = . , respectively). patients with proteinuria had significantly higher level of ldl-c compared to the patients with normoalbuminuria ( . ae . vs. . ae . mmol/l, p = . ). patients with microalbuminuria had significantly higher level of ldl-c compared to the patients with normoalbuminuria ( . ae . vs. . ae . mmol/l, p = . ), as well. the level of hba c in normoalbumiuric patients was significantly lower than in microalbuminuric ( . ae . vs. . ae . %. p = . ). there were no significant differences in levels of tg, hdl-c, vldl-c between patients with normoalbuminuria, microalbuminuria and proteinuria. conclusion: we showed that higher levels of ldl-cholesterol and tg were associated with microalbuminuria and proteinuria in patients with type diabetes. lowering atherogenic lipids may retard nephropathy progression in these patients. s. bonakdaran , b. kharaqani endocrine research center, mashhad university of medical sciences, mashhad, iran background: the relationship between elevated serum uric acid level and metabolic syndrome (ms) has been debated. we aimed to determine the prevalence of hyperuricamia and its association with ms in type diabetes mellitus (dm). methods: this was a cross-sectional study in diabetic patients. hyperuricamia was defined as uric acid ! and ! . mg/dl for men and women respectively. diagnosis of metabolic syndrome was based on atpiii criteria. clinical and biochemical parameters in hyperuricaemic and normouricaemic patients compared with other. results: the prevalence of hyperuricaemia and metabolic syndrome was . % and . % respectively. the prevalence of ms significantly increased in the highest quartile of uric acid levels compared with lowest quartile ( . % vs. . %, p < . ). serum uric acid had positive association with cholesterol, triglyceride, non-hdl cholesterol and a negative association with fasting blood sugar (fbs), glycosylated hemoglobin (hba c) and hdl cholesterol. possible biochemical predictors of hyperuricamia were cholesterol, triglyceride, creatnine and fbs. conclusion: the prevalence of ms and its components increase with increasing levels of uric acid in type diabetes. regular assessment of uric acid could give information for predicting of ms and prevention of atherosclerosis in type diabetes. materials and methods: in subjects (aged . ae . ) who have received recommendations on hypotensive and hypoglycemic therapy at diabetes school. psycho-correctional work has been carried out with people (group ) in order to increase treatment motivation and the work has not been carried out with people (group ). the effect has been evaluated after months according to the results of -h blood pressure monitoring ( -h bpm). results: according to moriski-green test % appear to be nonadherent to treatment. as a result only in group there has been recorded reduction in variability indices sbp (mm hg) at night ( . ae . vs. . ae . ; p = . ), daily index sbp ( . ae . vs. . ae . %; p < . ) and dbp ( . ae . vs. . ae . %; p = . ), rate in morning increase sbp ( . ae . vs. . ae . mm hg; p = . ) and dbp ( . ae . vs. . ae . mm hg; p < . ), which are high risk indicators of cardiocerebral catastrophe. after months of patients have become adherent to treatment in group (p = . ), only patients of in group (p = . ) (moriski-green test). conclusion: psycho-correctional training improves adherence to treatment, which is accompanied by positive dynamics of -h bpm indicators. introduction: quality of life is particular decreased in elderly with diabetes mellitus (dm), even not associated with other chronic illness. the purpose of the study was to analyze the quality of life in a group of elderly diabetic patients without major complications. the study group consisted of patients, males and females, aged over years old [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , diagnosed with type dm. they had no severe dm complication, nor other debilitating chronic diseases. the romanian version of the sf- questionnaire was used to measure quality of life (qol). diabetic subjects were compared with age-and gender-matched controls from a random standard population sample of the romanian population. results: reliability of scales by coefficient alpha cronbach was > . for all scales except social functioning. qol scores for study group were significantly lower compared with controls. there are no significant differences between patients following insulin therapy and patients with other therapeutic protocols. role limitations due to emotional problems correlate with disease duration and female gender. there is a significant correlation between energy/fatigue scores and female gender, hba c, fasting plasma glucose and obesity. there are no other statistically significant correlations between sf- scores and analyzed variables. discussions and conclusions: patients with dm have statistically significant impairment of all aspects of qol. dm put a substantial burden on affected individuals. insulin use didn't seem to have a negative impact upon qol. glycemic control is crucial in preventing long terms complications and provides better qol for diabetic patients. the study involved patients with nstemi and with ua hospitalized in cardiology department in . the data obtained from patients were statistically analyzed to determine the significance of the differences between the groups. results: glucose on admission was lower in patients with ua ( ae mg/dl) than with nstemi ( ae mg/dl), p = . . treatment of dm in patients with nstemi and ua shows figure . patients with nstemi presented lower left ventricular ejection fraction ( ae %) vs. ua ( ae %); p < . and higher mortality during hospitalization. seven patients ( . %) with nstemi died, whereas no patient died in ua group (p = . ). . to determine whether aaa patients found to be at higher risk of osa were also at increased risk for cardiometabolic disease, compared to those at low or no risk of osa. design: the berlin questionnaire to estimate osa was administered to elderly patients with or at increased risk of aaa disease along with several measures of cardiometabolic risk, including the lipid accumulation product (lap), a measure that combines triglyceride levels with central obesity (waist circumference), also known as hypertriglyceridemic waist. results: in this sample (n = ), subjects ( . %) scored clinically positive for risk of osa on the berlin questionnaire. next, individuals were separated into groups based upon the three subclasses of the berlin questionnaire: snore (frequent loud snoring), eds (excessive daytime sleepiness), and htn-bmi (hypertension and high bmi). the combination of snore + eds subclasses, when used to differentiate subject's risk levels for osa, was highly accurate for discriminating low, moderate, and high cardiometabolic risk, based upon significant differences in bmi, insulin (lu/l), waist circumference (cm), waist/hip ratio, low density lipoprotein cholesterol (ldl-c mg/dl), and lap (anova; p < . ). conclusions: these results give credence to the clinical use of the snore + eds portions of the berlin questionnaire to provide simple estimates of increased risk of t dm and cvd and/or need for further evaluation such as polysomnography or oral glucose tolerance. materials and methods: from to , t dm were cumulatively collected for study. accordingly, anthropometric and biochemical data, lifestyle measurements (lifestyle i : no smoking, no alcoholic and regular exercise; lifestyle ii : smoking and/or alcoholic and/or no exercise), total daily caloric intakes and macronutrient consumptions were recorded. the eating habits were classified by fat consumption, high fat diet (fat > %) and low fat diet (fat %). the mets defined was based on the atp iii criteria. patients were obligatorily classified into six groups, mets with waist component, waist required and non-waist required; mets without waist component, with two and more than two components; non-mets with waist and without waist component. each component of mets in these six groups with different combination of lifestyle and eating habit, were presented by case number and percentage distribution. or for the clustering of each metabolic component in these six groups were analyzed. results: the case number, percentage distribution and corresponding or for the clustering of each metabolic component in these six groups were shown in table and . the clustering of metabolic components of tg, hdl-c and bp were significantly higher in lifestyle ii, lifestyle i and high fat diet eaters respectively. objectives: early detection of metabolic syndrome is important in minimizing morbidity and motility. we conducted a study to detect wether serum leptin can be used as a biological marker to detect metabolic syndrome. methods: a group of healthy pre-menopausal females, aged - years was selected from the local community, randomly, stratified according to their bmi. leptin was assessed by the elisa method and, blood pressure was measured using digital blood pressure monitor and chemical analysis for fasting blood, glucose and lipid level were conducted using colorimetric method. body weight and height, hip and waist circumferences were measured, using standard protocols. in subjects with and without metabolic syndrome mean serum leptin values were . (ae . ) and . (ae . ) ng/ml respectively. compared with subjects without metabolic syndrome, subjects with metabolic syndrome had a higher serum leptin level (mean difference À . , and % confidence interval À . to À . , p = . ). conclusion: subjects with metabolic syndrome had a higher serum leptin level in comparison with subjects without metabolic syndrome therefore leptin can be utilized as a surrogate marker to predict metabolic syndrome. conducted a study to detect relationship between serum leptin and cardiovascular risk factors in obese and non obese individuals. methods: a group of healthy pre-menopausal females, aged - years was selected from the local community, randomly, stratified according to their bmi. body weight and height were measured, using standard protocols. serum leptin was assessed by elisa and, blood pressure was measured using digital blood pressure monitor and chemical analysis for fasting blood, glucose and lipid level were conducted using colorimetric method. results: there was a statistically significant inverse correlation between serum leptin level and mean blood pressure in obese (bmi ! ) individuals and subjects with systolic blood pressure > mmhg. corresponding r values were r = À . and r = À . (p < . for both). in subjects with bmi < or in normotensive subjects, there were no statistically significant correlations between serum leptin and mean blood pressure. correlations between serum leptin and total cholesterol, triglycerides, hdl, ldl, cho/hdl and fasting plasma glucose were . , . , . , . , . , . respectively and not statically significant (p . for all). conclusion: due to the presence of inverse correlation between serum leptin and mean blood pressure in obese, and individuals with high systolic blood pressure, it can be concluded that serum leptin may play a different role in pathogenesis of cardiovascular diseases in such individuals. r. irzma nski, j. błaszczyk, l. pawlicki, j. kowalski the aim: the aim of our study was to assess the influence of metabolic syndrome (ms) risk factors on vascular complications in patients with ms. material and methods: the study comprised patients ( women and men, avg. age . ae . years) with ms, which was diagnosed according to idf criteria . results: the prevalence of micro and macrovascular complications was assessed: vascular changes in the fundus of the eye - %, ischaemic heart disease - . %, egfr < ml/min - . %, diabetic foot - . %, cerebro-vascular accident - . % of patients. the negative correlation between hdl concentration, creatinine levels and level of vascular changes in the fundus of the eye was found. moreover the level of obesity and fasting glucose level had positive correlation with the intensitz of vascular changes in the fundus of the eye. objectives: to estimate malnutrition prevalence among newly hospitalized overweight/obese patients; to characterize malnutrition by body weight category; and to assess associations between bmi, duration of hospitalization and in-hospital death in malnourished patients. methods: this cross-sectional survey assessed nutrition status in all adults newly admitted to internal medicine and surgical departments at the e. wolfson medical center, holon, israel. data were recorded during the -week data acquisition period and screening for malnutrition risk was performed using the nrs . an age-adjusted score of ! on the nrs defined malnutrition. malnutrition was compared across body weight categories: underweight (bmi < . kg/m ), normal (bmi . - . kg/m ), overweight (bmi - . kg/m ) and obese (bmi ! kg/m ). overweight/obese subjects were compared by malnutrition status. results: a total of individuals were analyzed, of whom were overweight/obese (bmi ! kg/m ). of these, ( . %) were malnourished. compared to adequately nourished overweight/obese subjects, malnourished overweight/obese patients had significantly prolonged duration of hospitalization: . ae . (median , - days) vs. . ae . (median , - days), (p = . ). in-hospital mortality was . % among malnourished vs. . % among adequately nourished overweight/obese patients, p = . . malnutrition increased duration of hospitalization and in-hospital mortality risk in both overweight/obese and normal weight patients. discussion: malnutrition is a frequent finding in newly hospitalized overweight/obese adults. elevated bmi does not affect duration of hospitalization. in-hospital mortality rates are similar for normal weight and overweight/obese individuals. background: the purpose of this study was to examine differences in rmr in lean and obese subjects and to determine correlation between rmr and cardio metabolic risk factors. methods: ninety nine healthy subjects ( normal; obese and over weights) participated in this case-control study. sex and physical activity were matched. blood pressure, plasma insulin, glucose, homa-index, lipid profile, uric acid and c-reactive protein concentrations, anthropometric measurements, body composition, rmr and macronutrient intake were measured. result: fpg (p = . ), uric acid (p = . ), crp (p = . ), insulin (p < . ), homa index (p < . ), systolic and diastolic blood pressure (p = . ; p = . ), anthropometric measurements (except height and whr) (p < . ) and body composition (p < . ) were significantly higher in case group. there were no significant differences between both groups by the means of dietary intake. in obese and overweight group, rmr was statistically higher than control group (p = . ). there were no significant difference between both groups in adjusted rmr for ffm and fm (p = . ). with multiple linear regression, rmr was significantly associated with ffm (p < . ) and uric acid (p < . ) and negative significant correlation was observed between rmr and waist circumference (p = . ) and hdl (p = . ). the finding of a similarly specific metabolic rate in obese and lean subjects at first sight contradicts the idea that a low rmr is a main cause of obesity. one reason for the undetected association between low rmr and obesity may be that obesity-related metabolic risk factors mask the lower metabolic rate that initially contributed to weight gain. background: pain may cause some patients to avoid self-monitoring, which could impair glucose control. cooling the fingertip prior to puncture may reduce pain. objectives: to examine the efficacy of coolsense, a device designed to cool the fingertip prior to puncture for glucose self monitoring. methods: adults with type diabetes treated at the e. wolfson medical center diabetes unit outpatient clinic were randomized to treatment with the coolsense device or a sham device which appeared identical to the active intervention but did not cool the fingertip. patients completed a demographic and medical history interview and were asked to rate the device for discomfort and satisfaction. results: a total of patients were recruited and randomized to intervention group (coolsense vs. sham, n = in each group). participants were ae . years of age, had been diagnosed with diabetes ae . years prior to study onset and had mean hba c of . ae . %. patients reported performing . ae blood glucose checks per day. the extent to which glucose checking caused pain was rated at . ae . out of a possible five points, one being most severe. the coolsense device was a significant independent predictor of pain reduction, even after controlling for age, sex, hba c, aspirin, neuropathy and baseline rating of pain associated with glucose check. conclusions: cooling the fingertip with the coolsense device significantly reduced pain at the puncture site compared to a sham device. it is possible that this reduction in pain will increase glucose self monitoring events in patients with diabetes. f. saad , , a. yassin , , g. doros results: after years the following changes were observed: weight (kg) decreased by . kg from . introduction: testosterone treatment in hypogonadal men is standard therapy, particularly in younger men with congenital forms of hypogonadism. methods: three hundred thirty-three patients ( with primary hypogonadism including patients with klinefelter's syndrome, with secondary hypogonadism and with late-onset ("mixed" or "metabolic") hypogonadism aged - years (mean ae years) received intramuscular injections of mg of testosterone undecanoate during a maximal treatment time of years, overall corresponding to treatment years. hypogonadism was defined as total testosterone below nmol/l and occurrence of symptoms. physiological functions of bile salts include modulation of cholesterol and triglyceride metabolism, insulin sensitivity, the intestinal endocrine response to meals and energy homeostasis. several of these functions are mediated via the membrane g-protein coupled receptor tgr (also called gpbar and gpr ) which has been shown to promote release of glucagon like peptide- from enteroendocrine cells and increase energy expenditure in brown adipose tissue. methods: based on comprehensive discovery platform developed at satrx several in vivo active tgr inhibitors were discovered. active scaffolds were identified during the high throughput screening campaign of , tgr biased small heterocyclic molecules library that was optimized for medchem parameters and cell permeability. confirmed selective hits were evaluated for functional activity of glp secretion in nci-h endocrine cell line. in vivo activity was confirmed in db/db mice diabetes model. active compounds were administered chronically at doses , and . mg/kg and produced stable and statistically significant anti-diabetic effect. results: the most active compound showed efficacy comparable to mg/kg doses of sitagliptin. the actual activity data and experimental details will be provided. the interaction between excess of body fat (total and abdominal) and increased cardiovascular risk is well established in all age groups [ , ] . however, there are few studies that analyze the pattern of body fat distribution and its association with cardiovascular risk factors (crfs) in a population with more advanced age. objective: to analyze the presence of crfs according to the pattern of body fat distribution, in brazilian aged years or older. methods: one hundred and thriteen subjects, randomly selected, . ae . years, of both sexes. the percentage of total and abdominal body fat, hypertension and lipid profile were used for characterization of crfs. the chi-square test was used to assess proportions of crfs and mann-whitney test was used to compare the results between distributions of adiposity. results: eutrophic subjects showed lower triglycerides (p = . ), total cholesterol (p = . ) and prevalence of hypertension (p = . ) and hypertriglyceridemia (p = . ). subjects with higher abdominal adiposity showed higher total cholesterol (p = . ) and prevalence of hypertriglyceridemia (p = . ) and hypercholesterolemia (p = . ) than no excess of abdominal adiposity. higher value of one outcome already reflects the higher prevalence of hypertension (p = . ) and, the higher values of both outcomes reflect the high values of total cholesterol (p = . ) and triglycerides (p = . ). conclusion: that obesity, whether abdominal or total, is associated, in the same way, with dyslipidemia and hypertension in the subjects aged years. background/aim: there is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity and type diabetes mellitus (t dm) and cardiovascular complications. neutrophil-to-lymphocyte ratio (nlr) provides a simple method for assessment of inflammatory status and it is a new, inexpensive marker. the aim of the present study was to investigate the predictive value of preprocedural (before the ogtt) nlr on development of prediabetes (pd) and type diabetes (t dm) in morbid obesity patients (mop). methods: mop and normal weight patients with normal ogtt [fasting plasma glucose (fpg) < mg/dl. two-hour glucose during ogtt < mg/dl] were evaluated in this study. results: the mean ae sd nlr of mop were significantly higher than that of patients with normal weight healthy patients ( . ae . vs. . ae . , p < . , respectively). in receiver operating characteristics curve analysis, nlr > . had % sensitivity and % specificity in predicting pd and nlr > . had % sensitivity and . % sepesifity in predicting t dm. logistic regression analysis showed that elevated nlr (or: . , % ci: . - . , p < . ) was an independent variable for predicting t dm in mop. conclusion: mop have higher nlr than healthy controls. high nlr is a powerful and independent predictor of pd and t dm in mop. elevated nlr levels are usually considered as an inflammatory marker. the results of this study suggested that inflammation plays a role in the pathogenesis of pd and t dm with mop. division of human nutrition, wageningen university, wageningen, general surgery, rijnstate hospital, arnhem, gastroenterology, rijnstate hospital, arnhem, the netherlands objective: endoscopic implantation of a duodenal-jejunal bypass liner (djbl), or endobarrier, is a novel bariatric technique to induce weight loss and remission of type diabetes (t d). placement of the djbl mimics the duodenal-jejunal bypass component of the roux-en-y gastric bypass (rygb) procedure. as gut hormones are known to change substantially after rygb surgery, in our study we now evaluated gut hormone responses after implantation of the djbl. methods: fourteen (eight male, six female) obese t d subjects (bmi . ae . kg/m , duration of type diabetes . ae . years) were selected for implantation of a djbl. fasting plasma levels of glucose, c peptide, hba c and gut hormones ghrelin, gip and glp- were analysed before and at and days after djbl implantation. results: plasma hba c levels were significantly decreased after djbl implantation and a % reduction was found in diabetes medication usage (p < . ). ghrelin was found significantly elevated, with the highest induction in the first days post-implant. although the gip response showed high variation between subjects, gip tended to decrease days after implantation (p = . ). glp- levels showed a significant "dip" at day post-implant, which correlates with the intake of solely pureed/liquid food in the first week post-implant. conclusions: implantation of a djbl results in an early substantial remission of t d, comparable to results seen after rygb surgery. interestingly, in contrast to rygb surgery, implantation of the djbl seems to preserve normal physiological responses of gut hormones that are related to nutritional status. conflicting data exists as to the association between body mass index (bmi) and the rate of chronic kidney disease (ckd). in a cross sectional analysis of database from a screening center in israel we assessed the rate of ckd defined as estimated glomerular filtration rate (egfr) < ml/min per . m in relation to increasing bmi subcategories. the study population included , subjects, % women aged - , out of whom men and women had ckd. subjects with a bmi of - . (kg/m ) compared to subjects with bmi < (kg/m ), had an odds ratio (or) [ % confidence intervals (ci)] for ckd of . ( . - . ) and . ( . - . ) for men and women respectively. for subjects with a bmi of - (kg/m ) the or were . ( . - . ) and . ( . - . ) for men and women respectively. for subjects with bmi > (kg/m ) the or rose to . ( . - . ) and . ( . - . ) for men and women respectively. this association became insignificant in men after multivariate adjustment for age, hypertension and diabetes mellitus but persisted in women even after multivariate adjustment. the correlation between bmi and ckd in women was attributed to the subcategory of severely obese women with bmi above (kg/m ). our study suggests that for both men and women a positive correlation exists between the degree of bmi and the rate of ckd. this correlation persisted in severely obese women even after multivariate adjustment, suggesting that in women, obesity may be an independent risk factor for developing ckd. the enteroendocrine cell line pgip/neo stc- was used to evaluate the effects of gspe on glp- secretion in different nutrient conditions. a cytotoxicity detection kit (ldh) and brdu labelling and detection kit iii (roche) were used to determine cytotoxicity and cell proliferation, respectively. glp- levels in cell culture medium were determined using a glp- (active) elisa kit (millipore). cytotoxicity and proliferation cell assays (n = ) demonstrated that the maximum non-toxic gspe treatment for these cells was mg/l gspe over a period of h. surprisingly, after h of gspe treatment, glp- secretion (n = ) was significantly inhibited. this inhibitory effect was observed at concentrations as low as mg/l. furthermore, inhibition of glp- was also observed when stc- cells were co-incubated gspe and lmol/l dihomo-ϒ linoleic acid. in conclusion, acute gspe incubation decreases glp- secretion in cultured enteroendoncrine cells. interestingly the effect occurs under either on basal or nutrient (fatty acid) stimulated conditions. c. higa , f. novo , m.s. donato , n. rizzo , g. ciambrone , e. korolov , p. comignani coronay unit, hospital aleman, buenos aires, argentina introduction and aim: there is no data available respect of the prognostic value of albumin:creatinin ratio (acr) in non-st-segment elevation acute coronary syndrome (nseacs). the purpose of our study was to evaluate the long term prognostic value of acr in patients with nseacs. methods: we analyzed a prospective cohort of nseacs in whom acr was determined at admission. roc curves were constructed to determine best cut off value associated with primary end-point of death or nonfatal myocardial infarction (d/ami). independent variables for d/ami were assessed by a cox regression model. : seven hundred ten patients with nseacs were analyzed. thirty percent were female and median age was years. median follow up time was months. best cut-off point of acr for primary end point was mg/g. thirty-four percent of patients had acr ! mg/g. acr correlated with higher incidence of primary end point both in diabetics and in non-diabetic patients: or . (ic . - ), p = . and or . (ic % . - ), p = . , respectively. by multivariable cox regression analysis, acr was an independent predictor of d/ami at long-term follow up: hr . (ci % - ), log rank p < . in a model that included age, female gender, diabetes mellitus, serum creatinine, creatinine clearance, glucemia at admission a, elevated cardiac markers and st segment deviations. conclusions: acr was an independent predictor of adverse outcomes in nseacs. this simple and accesible marker should be considered for risk stratification in this high risk setting. aim of the work was to examine possible connection of methabolic syndrome with endothelium dysfunction in pre and postmenopausal women with and without ischemic heart disease (ihd). methods: hundred and eight-nine pre and postmenopausal women with ihd were examined and in same age without ihd. all women were measured arterial pressure using korotkov method (according to jnc- recommendations). vasa regulating function of endothelium examined with ultrasound in triplex scanning using reactive hyperemia probe (method by d. celermajer). willebrant factor determined in blood plasma. results: in group of women with ihd ( %) had arterial hypertension: among them ( %) in pre and ( %) postmenopausal. among women without ihd ( %) had hypertension: ( %) were pre-and ( %) postmenopausal. during reactive hyperemia probe diameter of radial artery was: women with ihd . ae . mm; speed of blood flow . ae . m/s, willebrant factor . ae . ; women without ihd corresponding . ae . mm (p < . ) and . ae . m/s (p < . ), willebrant factor . ae . (p < . ) where there significant difference was noted. findings allows us to suppose, that women with ihd have higher abundance of arterial hypertension, that in connection with other components of metabolic syndrome, specify development of endothelium dysfunction, in comparison with women without ihd, which have arterial hypertension, endothelium dysfunction infrequently. objective: recently, incretin-related drugs are widely used for improving blood glucose level in clinical practices. in this study, we tried to examine the efficacy and safety of these drugs of the japanese approved dose. we compared the efficacy and safety of the human glp- analogue liraglutide (the approved dose . mg) with the dipeptidyl peptidase- (dpp- ) inhibitor sitagliptin (the approved dose mg) once daily in the obese adults with type diabetes, over weeks. methods: japanese obese out-patients whose glycemic control was inadequately controlled with oral hypoglycemic agents received either maximum weeks of treatment with . mg lilaglutide (n = ) or mg sitagliptin (n = ) once daily within the period from march to october , at chubu-rosai hospital. the primary endpoint was change in body weight. other measurements were hba c, lipid profiles, body weight, body mass index, serum creatinine, estimated gfr, and adverse events before and at , , , weeks after liraglutide or sitagliptin administration. results: at the japanese approved dose, the greater reduction of mean body weight was achieved with liraglutide than with sitagliptin (À . kg, p < . , + . kg, p = n.s. vs. baseline). the degrees of lowering hba c (both . % at baseline) were À . % for liraglutide and À . % for sitagliptin (both p < . at baseline). the egfr of the sitagliptin group worsened from . to . ml/min/ . m (p < . at baseline). the most common adverse events were gastrointestinal symptoms ( ( %) patients on . mg liraglutide). conclusion: liraglutide provides greater body weight reduction over weeks even at the japanese approved dose of . mg. objective: to examine prevalence of cardiovascular risk factors in patients with type diabetes and stroke in primary care setting. methods: study was conducted at primary health center tuzla and included all patients with type diabetes and stroke who were registered in one family medicine team. we also calculated absolute cardiovascular risk according to the european guidelines on cardiovascular disease prevention in clinical practice. results: prevalence of stroke in diabetic patients was . %. significantly more women had stroke than men ( . % vs. . %; p = . ). mean age of patients was . ae . years. men were significantly older than women ( . ae . vs. . ae . ; p = . ). majority of participants belonged to age group > years ( . %). mean duration of diabetes was . ae . years. more than half of patients ( %) had diabetes - years, . % had diabetes - years, and . % patients had diabetes > years. family history for diabetes had . % patients. the most prevalent cardiovascular risk factors were hyperlipidemia ( . %) and hypertension ( . %). obesity was present in % patients, and . % patients had family history for premature cardiovascular disease. unhealthy diet had . % patients, . % were physically inactive, and % diabetic patients were smokers. mean absolute cardiovascular risk was . ae . %; . ae . % in men, . ae . % in women. men had significantly higher absolute cardiovascular risk than women (p = . ). conclusion: prevalence of cardiovascular risk factors in patients with type diabetes and stroke were very high. it indicates more effective strategies in primary care setting to reduce risk of macrovascular and microvascular complications. the prevalence of metabolic syndrome was determined as a crosssectional study among healthy saudi adults ( % males and % aged - years) attending national guard clinics using the definition proposed by ncep atpiii. the prevalence of metabolic syndrome was %. only one third of the participants had normal weight (bmi = . - . ). central obesity based on waist circumferences was noted in % of males and % of females. low hdl-c showed the highest prevalence ( %) followed by high tg ( %). about % of participants had impaired fasting blood glucose ( ! mg/dl). only % had high blood pressure ( ! / mmhg). more than three quarters ( . %) of the respondents had ! component of metabolic syndrome. in conclusion, metabolic syndrome needs to be addressed as an important health problem in the gulf region. background/aim: adequate treatment and monitoring of diabetes can significantly improve quality of life and extend life expectancy in diabetic subjects. aim of this study was to examine metabolic control in patients with type diabetes in primary care setting. methods: study was conducted at primary health center tuzla and included randomly selected patients with type diabetes, aged years and over, from one family medicine team. we evaluated parameters of metabolic control in patients with type diabetes according to the european guidelines on cardiovascular disease prevention in clinical practice. results: there were significantly more women than men ( . % vs. . %; p < . ). mean age of patients was . ae . years. mean duration of diabetes was . ae . years. only ( . %) patients had blood glucose < . mmol/l, and ( . %) patients had hba c < . %. controlled blood pressure / mmhg had ( . %) patients. only ( . %) patients had total cholesterol < . mmol/l, while ( . %) patients had triglycerides < . mmol/l. normal body mass index (bmi) < kg/m had ( . %) patients and recommended waist circumference ( . %) patients. mean blood glucose was . l ae . mmol/l, hba c . ae . %, systolic blood pressure . ae . mmhg, diastolic blood pressure . ae . mmhg, total cholesterol . ae . mmol/l, triglyceride . ae . mmol/l, bmi . ae . kg/m , waist circumference . ae . cm. conclusion: metabolic control of type diabetes in family medicine practice was inadequate which indicates more effective interventions in order to achieve appropriate metabolic control of diabetes and reduce risk of complications. aim: the aim of the study was to determine the metabolic responses to two different liquid milk protein diets in prediabetic and healthy volunteers. the diets were composed of . g whey or casein protein, g maltodextrin and g lactulose or . g maltodextrin and g lactulose (control). procedures: fifteen prediabetic and healthy volunteers consumed all liquid test diets with blood sampling over a h time period. blood glucose, incretin hormones, nefas, hydroxybutyric acid and plasma amino acids were analyzed. the feeling of hunger was determined using a visual analog scale. results: in both, prediabetic as well as healthy volunteers, postprandial blood glucose levels were significantly decreased and plasma insulin levels were significantly elevated with the protein diets compared to the control diet. gip and glp- levels also increased after the protein-contaning test-diets. in the prediabetic volunteers, changes in glucose, insulin, amino acids, non-esterified fatty acids and hydroxybutyric acid displayed time delayed changes. a reduced feeling of hunger was reported in the prediabetic compared to the control group. conclusion: both protein components elevate insulin secretion and cause reduced blood glucose auc and these effects are more pronounced in prediabetics. however, despite differences in the amino acid composition, casein and whey protein did not reveal significantly different effects. postprandial changes in plasma metabolites in prediabetics suggest more metabolic pertubations than just impaired glucose disposition. methods: ins- e cells or freshly isolated rat islets were incubated for h in the presence of either leptin or tnf-a at lower ( . nmol/l or ng/ml) or higher concentration ( nmol/l or ng/ml) individually or in combination. proinsulin mrna was detected by real time-pcr, insulin by radioimmunoassay kit, β cell proliferation were tested with mtt assay and β cell apoptosis was determined with annexin v-fitc/pi by fluorescent activated cell sorting. results: higher leptin ( nmol/l) or tnf-a ( ng/ml) significantly suppressed gsis (p < . ) and reduced the intracellular proinsulin mrna level and insulin content (p < . ) in ins- e cells and primary islets. whereas, lower leptin ( . nmol/l) or tnf-a ( ng/ml) did not show such effects. however, the inhibition effects were compromized when two factors were simultaneously administrated in either cultured ins- e cells or pancreatic islets. similarly, higher leptin or tnf-a was able to inhibit ins- e cell proliferation and promote cell apoptosis. again, these effects were alleviated in the presence of both factors. furthermore, western blotting showed that tnf-a inhibited leptin receptor (ob-rb) expression, decreased the phosphorylation of stat . conclusion: tnf-a exerts antagonistic effects on leptin actions in pancreatic β cells by interfering with ob-rb/jak/stat signaling pathway. increased tnf-a level may contribute to the pathogenesis of hyperinsulinemia and disturbed glucose metabolism in people with obesity. aims: identifying socioeconomic factors associated with the metabolic syndrome (mets) is useful to target preventive measures. our objective was to estimate, in france, the prevalence of metabolic syndrome (mets) and to investigate the association between socioeconomic position and mets. methods: the french national nutrition and health survey (enns) cross-sectional national multistage sampling was carried out from february to march . data included waist circumference and blood pressure measurements, blood sample and sociodemographic and medication information. the prevalence of mets was assessed using several definitions, including the most recent joint interim statement (jis). association with sociodemographic covariates was assessed using logistic regression models. results: among the participants - years of age, mets prevalence was found to vary from . % according to the national cholesterol education program definition to . % according to the jis definition, without difference between genders. after adjustment for other covariates, risk of mets increased with age in both men and women (for year: ora = . , p < À and ora = . , p < À ; respectively). in women, mets risk was inversely associated with education level; women with the lowest education level facing a six fold greater risk of mets (ora = . , p < À ). in men, risk of mets was higher in men born outside of france (ora = . , p = . ) than in french-born males. conclusions: mets prevalence is lower in france than in most industrialized countries. lifestyle modifications, targeted to migrants and persons living in low socioeconomic conditions, should contribute to further reducing mets. folate. patients were divided into two groups: group (homocysteine < lmol/l) and group (homocysteine ! lmol/l). results: the mean age was . ae . years. homocysteinemia was . ae . mmol/l. a significant correlation was found between homocysteine levels and the number of criteria for ms (p = . ). besides, a significant decrease of hyperhomocysteinemia (from . % to . %, p = . ), systolic blood pressure (from . ae . mmhg to . ae . mmhg, p = . ), uric acid (from . ae . lmol/l to . ae lmol/l; p < . ) and a significant improvement of hdl levels ( . ae . mmol/l to . ae . mmol/l, p < . ) were reported. a non significant improvement was observed for the other parameters. furthermore, a correlation was noted between the variation of homocysteine and hdl levels (p = . ). the association found between homocysteine and the severity of ms suggests a reflection on the cardiovascular risk caused by such association and on the importance of hyperhomocysteinemia screening in patients with ms. object of study and method: the patients with ms: of them presented with the recurrent form of af, had no arrhythmia. the groups were comparable in terms of age, concomitant disorders, arterial hypertension duration, arterial pressure, and severity of chronic heart failure. patients with permanent af, hemodynamically significant heart disease, myocardial infarction with wave q in the medical history, were excluded from the study. in a review of the diagnostic efficiency parameters showed statistically significant differences in the two groups, with the evaluation of their specificity (se), sensitivity (sp) and or (odds ratio). results: patients with ms having abdominal obesity and arterial hypertension over years (se . ; or . ( % . - . ); x = . ; p = . ); homa ir index more than . (se . ; or . ( % . - . ); x = . ; p < . ); reduced hdl cholesterol level below . mmol/l (se . ; or . ( % . - . ); x = . ; p < . ); left atrial dilation (se . ; or . ( % . - . ); x = . ; p = . ); albuminuria more than mg/day (sp . ; or . ( % . - . ); x = . ; p < . ); waist circumference more than cm (sp . ; or . ( % . - . ); x = . ; p = . ) were at high risk of af. the duration of abdominal obesity and hypertension for years, insulin resistance index > . , reduced hdl < . mmol/l, an increase in albuminuria > mg/day, an increase in waist circumference > cmrisk factors for af in ms. patients and methods: fifty-three patients with ms over , comparable in duration af, comorbidity and treatment. patients with permanent af, hemodynamically significant heart disease, myocardial infarction with wave q in the medical history, were excluded from the study. following a successful cardioversion all patients assigned amiodarone. group (n = ) in the adjuvant therapy prescribed metformin over - mg/day; group (n = ) metformin < mg/day, group (n = ) metformin is not assigned. the observation period is months. results: in group homairind decreased to . ae . (p < . compared with baseline), in the nd to . ae . (p > . ) and rd to . ae . (p > . ) (p - < . ), and improvement of lipid profile and increased gfr ( . ae . (p < . compared with baseline), . ae . and . ae . ml/min, in the st, nd and rd groups, p = . between groups); decreased volume of the left index atria ( . ae . (p < . compared with baseline), . ae . and . ae . ml, in the st, nd and rd); reduction in waist circumference ( . ae . (p < . compared with baseline), . ae . and . ae . cm, in the st, nd and rd). patients in group was maintained sr for much longer ( . ae . days) than in patients of the nd ( . ae . ) and the d group ( . ae . ) (p = . ; p - < . ; p - < . ). aims: metabolic syndrome (mets) is the serious health problem worldwide and is associated with increased risk of cardiovascular disease. mets has a significant genetic component which is estimated on - %. apolipoprotein a (apoa , omim acc. no ) gene and its variants have been associated with the plasma lipids, mainly triglycerides and its role in mets development is recently discussed. we have analyzed, if there is the association between the apoa gene haplotypes (based on the rs and rs variants) and mets in middle european -slavic population. methods: apoa haplotypes based on the presence of either common or at least one minor apoa allele (rs , c- and rs , g ) and the presence of mets were analysed in adults ( males and females, - years old) selected according the monica protocol and examined at / and / . the presence of mets was analysed according the ncep-atp iii criteria. results: in females with at least one minor apoa allele, the prevalence of mets was significantly higher both at / ( . % vs. . %, p < . ) and at / ( . % vs. . %, p < . ). in males, association between apoa gene and mets was not detected neither at / ( . % vs. . %, p = . ) nor at / ( . % vs. . %, p = . ). a. blazquez , o. garcia-sanchez , y. quiros , v. blanco-gozalo , m.j. montero , j.m. lopez-novoa , c. martinez-salgado , f.j. lopez-hernandez universidad de salamanca, ibsal, iecscyl-ibsal-university of salamanca, salamanca, spain diabetes commonly causes a type of chronic nephropathy, namely diabetic nephropathy (dn). diagnosis of dn is presently accomplished late in the course of disease. microalbuminuria anticipates progression towards dn only in a subset of patients. another subset of diabetic, microalbuminuric patients never develop dn. accordingly, new biomarkers are necessary to more accurately identify diabetic patients progressing towards dn. ngal has also been associated to progression to dn. on the other hand, hypertension is a well-known factor of co-morbidity in diabetic nephropathy. we decided to study the capacity of ngal to detect the additive effect of hypertension on progression to diabetic nephropathy. in the present work we aimed at unraveling the origin of the increased urinary ngal. spontaneously hypertensive rats (shr) or normotensive wistar rats were rendered hyperglycemic by a single administration of streptozotocin, or not (as controls). renal function was monitored and ngal was measured in urine, plasma and tissue samples. their kidneys were perfused in situ with krebsdextran solution (containing or not exogenous ngal), and urine was collected. plasma and renal tissue ngal was also measured by western blot, and renal ngal expression was determined by rt-pcr. our results suggest that the urinary ngal is increased by the coexistence of diabetes and hypertension, but not by each of these conditions. ngal excretion results from its altered tubular handling. this subtle and primary renal alteration might be studied further as an early marker of the increased risk of chronic renal disease posed by the co-morbidity of hypertension and diabetes. the increasing prevalence of obesity is a major public health concern. more than . billion adults, and older, were overweight, over million men and nearly million women of whom were obese in . large-scale studies have demonstrated that overweight and obesity increase the risk of developing several forms of cancer, including several that are not classically viewed as hormonedependent. in both men and women, increasing bmi is significantly associated with higher death rates from cancers of the oesophagus, colon and rectum, liver, gall bladder, pancreas and kidney, as well as non-hodgkin lymphoma and multiple myeloma. the associations between obesity and particular maignancies may be affected by body fat distribution, and may result from diverse factors including diet and abnormal levels of hormones and inflammatory cytokines. recently, there is more and more sufficient evidence that excess body weight is an avoidabl e cause of excess cancers including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal cancers. the mechanism that obesity association with cancer is remains not well understood. there are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors (igfs), sex hormones, adipocytokines, inflammatory cytokines, c-myc oncogenic transcription factor, obesity-induced hypoxia and warburg effect, and so on. in the future, the potential mechanisms and conclusions in obesity associated with increased risk for developing cancer, and the underlying cellular and molecular mechanisms will be studied. results: among patients with ms (mean age: years; % male), ( %) had abdominal obesity, ( %) had a c > . %, ( %) had fpg > mg/dl and ( %) had homa > . . if we consider as ir indicators: . presence of prediabetes criteria (fpg > mg/dl and/or a c > . %); and/or . homa > . , patients ( %) met at least one marker of ir, but of them ( %) had homa < . [ ( %) of them were on therapy with metformin, an insulin-sensitivity drug]. in the multivariate analysis, presence of type diabetes (hr . ; p < . ) and presence of prediabetes criteria (hr . ; p < . ) were associated with homa > . discussion: although most of the patients with ms have clinical markers of ir (fpg > mg/dl, a c > . %), only a third part of them have homa levels associated with ir. these observations suggest that: of spilberger's test. from to women were followed for the incidence of ah. results: high level of anxiety (hla) in studied cohort revealed in . % of women. women with hla more often tried unsuccessfully to quit smoking compared to lower levels of anxiety ( . % and . %, respectively; x = . , p < . ). women with hla in twotimes less likely to follow the diet (x = . , p < . ) and assess their physical activity more passive (x = . , p < . ). relative risk (hr) of development of ah in women with hla during the first years of study was in . -fold higher ( . % ci: . - . ; p < . ), over years it was . ( . % ci: . - . ; p < . ) and hr was . ( . % ci: . - . ; p < . ) over years of follow-up compared to those with lower anxiety levels. depending on age groups the risk of ah incidence within years was highest in older group with hla aged - years (hr = . ; . % ci: . - . , p < . ). conclusions: there is high prevalence of hla in russian female population aged - . during years of follow-up women with hla have significantly higher risk of ah especially in older age groups. material and methods: under the third screening of the who "monica-psychosocial" (mopsy) program random representative sample of women aged - years (n = ) were surveyed in novosibirsk. d was measured at the baseline examination by means of test "mmpi". from to women were followed for years for the incidence of ah. results: the prevalence of d in women aged - years was . %. women with major d ( %) significantly extended negative behavioral habits: smoking and unsuccessful attempts to give it up, low physical activity, they were less likely to follow a diet. relative risk (hr) of ah in women with d during the first years of study was higher in . -time compared to women who had no d ( . % ci: . - . ; p < . ). with regard to age groups hr was significant in oldest age category - years (hr = . ; % ci: . - . ; p < . ). hr of incident ah in persons with d within years was . ( . % ci: . - . ; p < . ) and there were no significant differences in age groups. we did not have risk of ah over years of follow-up in women with d (p > . ). the prevalence of d in women aged - years is more than %. women with d had unfavorable lifestyle and higher relative risk of ah over the first - years of the study. purpose: study the association of high level of anxiety (hla) with vntr polymorphisms d and dat genes; determine the relative risk (hr) of arterial hypertension in men with hla. the who " monica-psychosocial" in monica-psychosocial" in , monica-psychosocial" in , surveyed a random representative sample of men aged - years ( men). to assess the level of anxiety was used spielberger's test. cox proportional regression was used for hr assessment. results: the hla in an open population of men aged - years was . %. since hla genotype was significantly associated / drd gene and genotype / gene dat. for years hla maximizes the hr of hypertension in the first years. conclusion: there is high prevalence of hla at male aged - in russian. hla were significantly associated with certain vntr polymorphisms of genes drd , dat; hla increases the hr of hypertension in the first years. inhibiting beta cell proliferation and promoting its apoptosis which concomitantly leads to decreased β cell mass. dermatology, faculty of medicine, cairo university, cairo, egypt background: psoriasis is a disorder with genetic and immunologic background. leptin can regulate the t-helper response. objective: our primary goal is to study the functional polymorphism (g- a) of the leptin (lep) gene in the genetic predisposition of psoriasis, and our secondary goal is to examine factors affecting plasma leptin levels in psoriasis, and to compare patients with and without metabolic syndrome (ms). methods: the study involved psoriatic patients and healthy controls. analysis of g- a polymorphism of the lep gene was made by the pcr and restriction fragment length polymorphism technique. the relationship between lep gene polymorphism and the clinical features of the patients was analyzed. plasma leptin levels and proportions of comorbidities in patients vs. controls were compared. results: in controls the ga, aa and gg frequencies were %, % and % respectively, while in patients the distribution of genotypes was . %, . % and . % respectively, with significant difference (p = . ) between patients and controls. in patients with ms the gg, ga and aa frequencies were . %, . % and . % respectively, while in patients without ms the distribution of genotypes was . %, % and . % respectively, with significant difference (p = . ) between both groups. plasma leptin showed a significant higher levels in the patients vs. the controls (p < . ), and among the different lep genotypes (p < . ) in the patients′ group. conclusion: lep g- a polymorphism could be a predictor for higher plasma leptin and increased risk of psoriasis and could be used as a marker for psoriasis-related comorbidity risk. introduction: contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in diabetic heart. aims: the aim of this study was to investigate the pattern of mrna encoding cardiac muscle proteins that are involved in the process of excitation-contraction coupling in early onset type diabetic goto-kakizaki (gk) rat. methods: experiments were performed in gk and wistar control rats aged - weeks. gene expression was assessed in ventricular muscle with real-time rt-pcr, shortening and intracellular ca + were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. results: expression of genes encoding some membrane pumps and exchange proteins were unaltered (atp a / , atp b , slc a ) whilst others were either upregulated (atp a ) or downregulated (slc a ) in gk ventricle compared to control. expression of genes encoding some calcium (cacna c/ g, cacna d / d , cacnb /b ), sodium (scn a) and potassium (kcna / , kcnj / / / / , kchip , kcnab , kcnb , kcnd / / , kcne / , kcnq , kcng , kcnh , kcnk , kcnn ) channel proteins were unaltered whilst others were either upregulated (cacna h, scn b, hcn ) or downregulated (hcn , kcna , kcna , kcnj ) in gk ventricle compared to control. the amplitude of ventricular myocyte shortening and intracellular ca + transients were unaltered however, the tpk shortening was prolonged and thalf decay of the ca + transient was shortened in gk myocytes compared to controls. conclusions: early changes in expression of genes encoding various cardiac muscle proteins are associated with disturbances in myocyte shortening and intracellular ca + transport. results: analysing level of tnf-alpha, we found that in group , there were significantly higher values than the control group by . times ( . ae . pg/ml: . ae . pg/ml, respectively), and significantly higher than patients without insulin resistance ( . ae . pg/ml). analyzing level of il- , the presence of ir, level of this cytokine increases by only a factor of ( . ae . pg/ml) relative to that of the control group ( . ae . pg/ml). in the second group, the level of il- ( . ae . pg/ml) was significantly higher than in group and exceeded the performance of control group by . times. analyzing the ratio of the level of tnf-alpha and il- , we have detected a significant increase in the coefficient tnf-alfa/il- in group ( . ae . ) compared with group patients ( . ae . ). that is, ir in chc patients gives a significant shift in balance of cytokines toward proinflammatory interleukins, which can be observed by increase of tnfalfa/il- over . (p < . by mann-whitney). conclusions: progression of ir in patients with chc is accompanied by an increase in ratio tnf-alfa/il- serum. beyond the value of . , chc patients will an require in-depth study for carbohydrate metabolism. cardiovascular medicine, international university of health and welfare sanno hospital, tokyo, japan background: hyperglycemia has been suggested as a significant factor in coronary microangiopathy in patients with type diabetes (t dm), but whether it can be reversed through treatment of hyperglycemia is unknown. aim: to clarify whether glycemic control can improve coronary microangiopathy in t dm. methods: subjects were t dm who underwent coronary angiography and age-matched controls. myocardial segments perfused by angiographically normal coronary arteries were studied. baseline myocardial blood flow (mbf, ml/min/ g) and mbf during dipyridamole administration ( . mg/kg/min) were measured using positron emission tomography (pet). myocardial flow reserve (mfr) was calculated by the ratio of mbf during dipyridamole administration to the baseline mbf. after the first pet study, patients were subdivided into an additional intensive therapy group (atg) and no-additional therapy (natg) group. second pet scan was performed - months later. results: baseline mbf was comparable among the atg ( . ae . ), natg ( . ae . ) and controls ( . ae . ). however, mbf during dipyridamole administration was significantly lower in both the atg ( ae . ) and natg ( ae . ) than in controls ( ae , p < . ) as was the mfr (atg, . ae . ; natg, . ae . ; controls, . ae . ; p < . respectively). mfr was significantly improved in the atg ( . ae . ; p < . ), but not in the natg ( . ae . ; p = ns). there was a significant inverse relationship between percent change in mfr and percent change in glycemic control. however, no significant relationships were seen between the percent change in mfr and percent change in plasma lipid fractions. conclusion: coronary microangiopathy in t dm can be reversed by intensive therapy for hyperglycemia. l. drimba, r. s ari, j. né meth, z. szilv assy, b. peitl background: our aim was to investigate the effect of "sui generis" hyperinsulinaemia on proarrhythmogenic electrophysiological changes and on cardiac arrhythmias. methods: euglycaemic hyperinsulinaemia was induced in chronicallyinstrumented conscious rabbits equipped with a right ventricular pacemaker electrode catheter. hyperinsulinaemia was induced by either or mu/kg/min insulin infusion and a variable rate of glucose infusion ensured the maintenance of euglycaemia ( . ae . mmol/l). the effect of hyperinsulinaemia on cardiac electrophysiological parameters and arrhythmia inducibility was studied by means of -lead surface ecg recording and by programmed right ventricular stimulation (prvs). the role of adrenergic activation was investigated by determination of plasma catecholamine level and by intravenous administration of beta adrenergic blocking agent, propranolol. results: both and mu/kg/min insulin infusion prolonged the pq and the tpeak-tend intervals and shortened the rverp, but no significant changes on other measures of ecg (hr, qt, qtc) were observed. the incidence of prvs-induced ventricular premature beats and non-sustained ventricular tachycardia was higher during euglycaemic hyperinsulinaemia than that of fasting state. we found that higher plasma level of insulin was occurred, the more inducibility of arrhythmias was seen. no change in plasma catecholamine level was observed, but the propranolol restored the prolonged tpeak-tend interval. our results indicate the "sui generis" proarrhythmic effect of hyperinsulinaemia due to reduction of the repolarization reserve in otherwise healthy rabbits. propranolol can be used safely for prevention of arrhythmia in patient with hyperinsulinaemia. euglycaemic hyperinsulinaemia is suitable method to induce acquired long qt syndrome in healthy rabbits. objective: this study investigated the prevalence of metabolic syndrome (mets) and its association with demographic, socioeconomic and behavioral factors in shift workers. a cross-sectional study was conducted on a sample of shift workers of both sexes in a poultry processing plant in southern brazil. the diagnosis of mets was determined according to the recommendations from "harmonizing the metabolic syndrome". the distribution of each of the components of mets was evaluated according to the demographic, socioeconomic and behavioral characteristics of the sample. the multivariate analysis followed a theoretical framework for determining mets on shift workers. the prevalence of mets on the sample was . % (ic % : . - . ). the most frequent altered component was waist circumference (rp . ; ic % . - . ). after adjustment, the prevalence of mets was positively associated with women (rp . ; ic % . - . ), workers of over years of age (rp . ; ic % : . - . ) and those who reported sleeping five or less hours per day (rp . ; ic % : . - . ). on the other hand, mets was negatively associated with higher educational level (rp . ; ic . - . ) and having more than three meals per day (rp . ic % . - . ). in addition, most of the altered components of mets were associated with sociodemographic characteristics, whereas only waist circumference and altered blood pressure were associated with behavioral characteristics. conclusion: sex, age, educational level, eating habits and duration of sleep appeared as independent risk factors for mets. arab world covers a vast geographic area, consists of countries with an approxiimate population of about million people. geographically, arab world is variable ranging from dry desert areas to heavily raining green land. this part of the globe is also unique for its wide cultural, social and ethnic variations. most of the countries are well-heeled with significant natural resources including oil, gas and are benefited from high income. the socio-economic progress has brought benefits in the region such as improved access to health care, education, and safe drinking water. this rapid economical change has also set the scene for the modern lifestyles activities, people are eating more and exercising less. these changes in the lifestyle cause variuos metabolic syndromes including obesity, diabetes mellitus. in spite of marvelous advancement in medical sciences, the most of the metabolic syndromes are still an incurable life-long disease and swiftly increasing in all over the world. presently, six countries including saudi arabia, bahrain, united arab emirates, kuwait, oman and egypt are among the world's highest for the prevalence of metabolic syndromes especially the diabetes mellitus. metabolic syndromes placed a great burden on the public health and clinical practice in the region. v. negrean , o. mislea , i. cheta , t. alexescu , i. chisalita internal medicine, umf iuliu hatieganu cluj-napoca, cluj-napoca, umf 'victor babes' timisoara, timisoara, romania introduction: it is known that type diabetes is a major cardiovascular risk factor, but the relationship between impaired fasting glucose (ifg) and the occurrence of cardiovascular events is still undefined. objectives: to determine whether the ifg is a risk factor for cardiovascular disease. results: twenty-four percent of the patients with ifg progressed to diabetes and % from the control group were diagnosed with this condition. twenty-one percent of the patients with ifg and % from the patients in the control group were diagnosed with hbp. sixty percent from the patients with ifg and % of the patients in the control group were obese, % from the subjects with ifg and % from the subjects in the control group show ischemic heart disease. fifty-five from the patients with ifg and % from the patients in the control group declared that they practice no physical activity. there was a significant correlation between the presence of ifg and the hbp (or = , p < . ), the absence of physical activity (or = , p < . ), obesity (or = , p < . ), ischemic heart disease (or = , p < . ). conclusions: our study shows that ifg is correlated with the cardiovascular risk: patients with ifg have three times higher risk to develop hbp, six times higher risk to be obese and three times higher risk to have ischemic heart diseses. introduction: : the most common investigated factors in chronic inflammation in type diabetes are increased c-reactive protein level, erythrocyte sedimentation rate. the matrix metalloproteinases are a family of proteolytic molecules which contribute to adipose tissue abnormalities. metalloproteinase (mmp- ) has a significant contribution to development of complications of diabetes. aim: : the assessment of the inflammation intensity in patients with type diabetes mellitus and the examination of mixed meal influence on mmp- plasma level. materials and methods: : twenty subjects were qualified to this study. all of them were diabetics on insulin treatment. concentrations of mmp- were estimated at fasting state and after mixed meal challenge (elisa). we also measured body mass, bmi, systolic and diastolic blood pressure and: esr, crp, daily average glucose, hba c. results: : mmp- concentration values were higher in fasting state in comparison to in postprandial state. mmp- correlates with esr, crp, bmi, average daily glucose level and body weight. however, there are no significant correlations between mmp- and hba c. conclusions: : there was a statistically significant positive correlation between serum metalloproteinase and exponents of inflammation, such as erythrocyte sedimentation rate, c-reactive protein. after the mixed meal we observed a significant decrease of metalloproteinase concentration in relation to its concentration in the fasting state. it was shown that the concentration of metalloproteinase depends on short-term metabolic control of type diabetes, not depending on long-term control of the disease. background: several studies suggest increased oxidative stress and reduced endothelial function in obstructive sleep apnoea syndrome (osas). we assessed the association between osas, endothelial dysfunction and oxidative stress. the effect of nasal continuous positive airway pressure (ncpap) on oxidative stress and arterial dysfunction was also evaluated. we studied consecutive patients with heavy snoring. patients underwent overnight home polysomnography. ten patients with severe osas were revaluated after months of ncpap therapy. oxidative stress was assessed by measuring urinary -iso-pgf a and serum levels of soluble nox -derived peptide (snox -dp). serum levels of nitrite/nitrate (nox) were also determined. flow-mediated brachial artery dilation (fmd) was measured to asses endothelial function. results: polysomnographic indices were correlated with the metabolic score, insulin levels and central obesity indices. severe osas had higher urinary -iso-pgf a (p < . ) and serum nox and lower nox. a negative association was observed between fmd and osa severity. apnea/hypopnea index was correlated with urinary isoprostanes (r = . , p < . ). metabolic syndrome (t = À . , p < . ) and urinary -isoprostanes (t = À . , p < . ) were the only independent predictors of fmd. after -months of ncpap treatment, a significant decrease of serum nox , (p < . ) and urinary -iso-pgf a (p < . ) was observed, while serum nox showed only a minor increase. a statistically significant increase of fmd was observed (from . % to . %). conclusions: our study indicates a strong association between osas and metabolic syndrome. patients with osas and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by ncpap treatment. pendyffryn medical group, prestatyn, diabetes centre, royal liverpool university hospital trust, liverpool, uk introduction: metabolic syndrome (mets) and low testosterone levels are independently associated with increased all-cause and cardiovascular mortality. low testosterone levels are associated with obesity, insulin resistance and an adverse lipid profiles in men and the metabolic syndrome and type diabetes have a high prevalence of testicular hypogonadism. the relationship and interaction between these conditions and the potential affect they have on each other is not fully understood. method: this study examined the correlation between testosterone and the criteria of the metabolic syndrome in subjects (age . years, ae . ,( - . ) (mean, sd (range)), total-testosterone . nmol/l, ae . ,( . - ), free-testosterone . nmol/l, ae . , ( . - . ), sex hormone-binding globulin level . nmol/l, ae . , ( - ). correlation and significance statistical testing used the pearson correlation coefficient. results: diabetes was present in . % and a further . %( / ) had the metabolic syndrome. total-testosterone, free-testosterone and shbg had significant and the strongest correlations with age (r = À . , À . . . respectively, p < . ). shbg had the strongest negative correlations with triglycerides (r = À . ), waist circumference (r = À . ) and hba c (r = À . ), (total-testosterone, triglycerides (r = À . ), wc (r = À . )), all significant p < . . there were positive correlations with hdl (r = . shbg, r = . tt, p < . ). there were no significant correlations with blood pressure and free-testosterone had no correlation with mets criteria. conclusion: lower testosterone levels have the greatest correlation with ageing but are also associated with detrimental changes in central adiposity and dyslipidaemia. shbg rises with age, however lower levels have a stronger association with cardiovascular risk. this study suggests that cardiovascular risk and androgen abnormalities might be methods: group (gr ) was composed of normal subjects (age = . ae . ; means ae sem). group (gr ) consisted of non-obese type ii dm pts with hypertriglyceridaemia (type iv hlp) and ath (age = . ae . ). group (gr ) consisted of nonobese type ii dm pts with mixed hyperlipidaemia (type iib hlp) and ath (age = . ae . ). following have been determined in serum, in fasting state: total cholesterol (ch), hdl-cholesterol (hdl-ch), atherogenicity coefficient (hac), triglycerides (tg), lipolytic activity (la), lipoprotein fractions, prostaglandins a and e , prostaglandins f alpha (pgf). following have been determined in plasma, during standard ogtt: glucose, insulin, insulin/glucose index (igi), glucagon, c-peptide, sth, somatostatin, acth, cortisol, aldosterone, beta-endorphin. results: both gr and gr pts, compared to gr , had higher body mass, ch, tg, hac, and lower hdl-ch, la, insulin (at ogtt hour ), igi, sth (hour ), basal aldosterone. gr pts, compared to gr , had lower sth (hours and ). gr pts, compared to gr , had higher glucagon (hour ), somatostatin (hours and ), cortisol (hours and ), pgf, and lowerc-peptide (hour ), sth (hours and ). conclusions: altered hormonal-metabolic patterns have been observed in non-obese type ii dm pts with ath and dyslipidaemias, including decreased sth and elevated cortisol. hyperlipidemia has been indicated as an important factor of contributing to diabetes progression. however, whether native ldl or modified ldl causes dysfunctional effect of insulin secretion in islet cells is still elusive. the present study aims to identify the mechanisms of electronegtive ldl (l ) and l (less electronegtive ldl) acting on the insulin secretion of pancreatic β-cells. rin-m f cells, were cultured in the complete medium with human native l , l , or oxldl. the intracellular concentration of reactive oxygen species (ros) measured by use of dcfhda was significantly increased after loading l ( lg/ml) or oxldl ( lg/ml), but not effected after loading l ( lg/ml). the cell viability assayed by prestoblue tm reagent was suppressed to % after loading l or oxldl; however, l did not inhibit the cell viability. the insulin release of rin-m f cells was determined by elisa kit. our results demonstrated that % decrease of secretion ratio in the phase of high glucose-induced response after the β-cells were exposed in l for h as comparison with in normal medium. we also found that phosphor-c-jun was activated after loading l or oxldl, but not after loading l . the activation of c-jun may modulate the gene expression or the process of insulin secretion. thus we suggest that l , not l , is the main subparticle which induces oxidative stress and then lead to dysfunction of insulin secretion responding to high glucose stimulation in β-cells. target group for diet and physical activity interventions due to their increased risk of post-natal weight gain, type diabetes and related health problems. postpartum weight gain and/or retention, particularly in the first months are commonly due to lack of nutrition knowledge, poor dietary habits and physical inactivity. mothers are also integral to the shaping of attitudes and eating and activity behaviours of their children. the proposed study will evaluate whether an individualized weight management program with nutrition and physical activity advice and support enhances weight loss compared with standard care in overweight and obese women and women with a history of gdm. it is hypothesized that, compared with individuals given standard diet and physical activity advice, overweight and obese women, and women with a history of gdm prescribed exercise energy expenditure targets and using heart rate (hr) and dietary intake monitoring with electronic reminders, are better able to achieve a target weight loss ( % reduction from prepregnancy weight for overweight or obese pregravid ( ! . kg/m ), for overweight women ( . - . kg/m ) to achieve a weight loss that places them in the healthy-weight range, and for women who were in the healthy-weight range pregravid to return to their prepregnancy weight) through changes in eating and activity behaviours. objective: diabetes is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. we used high-fat and sugar diet and streptozotocin induced diabetic rats to observe the changes of proteins of insulin signaling which closely correlate with learning and memory. we try to illuminate the possible mechanisms of learning and memory decreased in t dm. methods: a total of rats were randomly divided into two groups: control group (c), diabetes mellitus group (dm). after weeks, morris water maze was used to perform training trial and probe trial in order to detect spatial learning and memory abilities. and we detected proteins of insulin signaling such as ir, irs- , akt, p-creb and bcl- in the hippocampus of the rats by western blot and immunohistochemistry staining. results: . water maze experiment: compared with the c group, the escape latency increased significantly in dm from the nd day. in the spatial probe experiment, the first time passing hidden platform prolonged significantly and the distance swimming in the quadrant of hidden platform decreased significantly in the dm. . immunohistochemistry staining: compared with the c group, the positive neurons of ir, irs- , akt, p-creb, bcl- increased in the dm group. . western blot: compared with the c group, the expression of ir, irs- , akt, p-creb, bcl- increased in the dm group. conclusions: the learning and memory ablities decreased, while the expression of ir, irs- , akt, p-creb, bcl- abnormal increased in t dm model rats. the results indicate that insulin signal transduction were impaired in t dm. objectives: niacin, a widely used lipid-modifying drug, is known to induce hyperglycemia during prolonged and high-dose treatments. however, its potential mechanism (s) whereby the islets are involved remains to be determined. we thus aim to investigate the potential role of niacin and its receptor gpr a involved in regulating islet beta-cell function and insulin resistance. methods: hfd-induced obese mice were employed to study the in vivo effects of niacin. blood glucose/serum insulin levels, oral glucose tolerance test (ogtt)/insulin tolerance test (itt), and homeostasis model of assessment-insulin resistance (homa-ir) were performed to assess glucose homeostasis. real-time pcr, western blot and immunefluorescent assays were used to study the expression of genes of interest. cyclic adenosine monophosphate (camp) and glucosestimulated insulin secretion (gsis) from isolated islets and ins- e beta cells were determined. knockdown of the gpr a in ins- e cells was also examined and compared. results: eight-week treatment with niacin increased blood glucose levels by % in hfd-induced obese mice while the areas under curve of ogtt and itt, and homa-ir index were consistently enhanced. in addition, niacin treatment significantly decreased gsis in isolated pancreatic islets. ex vivo and in vitro studies showed niacin decreased gsis, increased mrna expression of ucp and gpr a as well as inhibited intracellular camp accumulation in ins- e cells. in corroboration, the decrease in gsis and camp levels were abolished by the knockdown of gpr a. our data indicate that niacin treatments leads to hyperglycemia and impaired pancreatic islet function, which is probably via the activation of islet niacin receptor gpr a-induced pathway. a once daily glp- analogue, liraglutide, is emerging world-wide as a drug for the treatment of diabetes and also, potentially, obesity. this agent not only acts on glycemic control, but also exerts an effect on body weight control, because liraglutide inhibits gastric emptying, resulting in appetite reduction and lower energy intake. herein, we treated type diabetic obese subjects with . mg/day liraglutide and examined glycemic control and body weight changes over a month period. glycemic control was markedly improved (baseline hba c . ae . %, endpoint hba c . ae . %) with liraglutide. based on subgroup analysis, the good responders to liraglutide were ( ) bmi < . ( ) diabetes duration < years. ( ) postprandial cpr < . ng/ml. while liraglutide-induced gastric symptoms, specifically nausea, occurred in nearly all patients at baseline, it had disappeared in about half by the end of the study. unexpectedly, the hba c improvement was not associated with the presence of nausea. while acute body weight loss ( . ae . kg) was observed at month, there were no significant body weight changes at the end of the study. individual body weight change was associated with the presence or absence of nausea at the end of the study. in conclusion, the effects of liraglutide on body weight loss lasted only a short period and no chronic effects were observed. thus, the hba c lowering effect of liraglutide is not due to reduced energy intake, but rather, to recovery from defects in postprandial insulin secretion. background and aims: durability of good glycaemic control may delay development of diabetic complications. early initiation of combination treatment with oral anti-diabetic drugs (oads) having complementary mechanisms of action may increase durability of glycaemic control compared with stepwise addition of oads. dpp- inhibitors such as vildagliptin are good candidates for early use in combination with metformin as they are weight neutral with no additional risk of hypoglycaemia. materials and methods: about drug-na€ ıve patients with type diabetes mellitus (t dm) with hba c between . and . %, will be randomised in verify, a -year, multinational, double-blind, parallel group study. the study will test the hypothesis whether early combination therapy with vildagliptin/metformin will result in lower treatment failure rate or in lower rate of loss in glycaemic control over time than with metformin alone. other objectives include evaluation of rate of fasting plasma glucose progression, change in hba c over time, time to insulin initiation, development/progression of diabetic complications, changes in weight, changes in homa-β/ir, safety and tolerability. insulin secretion rate and insulin sensitivity will be assessed in annual standard meal-test. patients will also be evaluated for early changes in the vasculature, microalbuminuria and retinal microaneurysms. results and conclusions: verify is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin followed by addition of oads. verify will provide valuable data on the durability of glycaemic control, βcell function, insulin resistance, safety and tolerability and explore early changes in the vasculature of patients with t dm. patients with metabolic syndrome are at high risk for developing atherosclerosis. recent studies have suggested glucagon-like peptide- (glp- ) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. on the other hand, pparc activation was demonstrated to inhibit the transcription of factors, such as nfjb, resulting in atherosclerosis prevention via suppression of the expressions of cytokines and adhesion molecules in endothelial cells. we investigated whether pparc activation is involved in the glp- -associated antiinflammatory action in endothelial cells. we constructed an adenovirus expressing the ppre (+)-luc reporter gene for use with the reporter assay system. when we treated huvec cells with . nmol/l exenatide, endogenous pparc translational activity was significantly elevated by % as compared with control cells. the maximum pparc activity enhancing effect of exenatide was observed h after the initiation of exenatide incubation and was approximately % of that induced by lmol/l pioglitazone. when incubated with exenatide and pioglitazone simultaneously, pparc activity was additively promoted, suggesting that these two agents synergistically stimulate pparc activity. as h , a pka inhibitor, abolished glp- induced pparc enhancement, the signaling downstream from glp- cross-talks with pparc activation. in conclusion, our results suggest that glp- has the potential to induce pparc activity, partially explaining the anti-inflammatory effects of glp- on endothelial cells. cross-talk between glp- signaling and pparc activation would confer major impacts on treatment of patients at high risk for cvd events. in the rat hypothalamus by adenovirus-mediated gene transfer and then examined phenotypes of the rats. dnlkb significantly inhibited the thr phosphorylation of ampk alpha subunits, while wtlkb did not alter phosphorylation, suggesting that hypothalamic ampk is activated in basal states and negatively regulated by dnlkb . dnlkb -overexpressing rats exhibited body weight gain and slight insulin resistance as compared with wtlkb -overecpressing or sham operation-rats. taking into consideration that food intakes did not differ among these rats, this effect was probably due to reduced energy expenditure. in fact, the adipose tissue in dnlkb -overexpressing rats produced smaller amounts of pgc alpha and ucp , resulting in increased adipose tissue weights, as compared with wtlkb overexpresing rats. neither hepatic fatty acid synthesis nor gluconeogenesis was significantly altered. the phenotypes observed in dnlkb -overexpressing rats appear to be like those of ampk alpha deficient pomc neuron mice. in conclusion, our findings demonstrated inhibition of hypothalamic lkb to lead to reduced energy expenditure and body weight gain, suggesting that central lkb is involved in bodyweight regulation probably via ampk modification. material and method: anthropometric variables and lipid related factors concentration were measured. pcr and rflp were performed. the distributions of a polymorphic site and its relationship with mentioned factors were examined. result: in normal subjects there wasn't any relationship between these three polymorphism and studied profile, but in females with mets, presence of g allele in rs significantly increase diastolic blood pressure, low density lipoprotein and apolipoprotein a (apo a ) level and the c allele in rs , increase waist circumference, triglyceride and apo a level. while previous studies in adults demonstrated that snps in apoa , have primarily been associated with plasma lipoprotein levels and associated downstream consequences, such as weight gain and heart disease risk, in present study we find that there are some relation between this variation and lipid profile in female with metabolic syndrome and this relationship is sex dependent. tryglicerides mean value was mg/dl and cholesterol mg/dl; the mean value was slightly elevated but inside the lot of the patients the variations were wide probably due to liver inssuficiency (low values) and alcooholic etiology of underlying liver disease (higher values). serum uric acid had a mean value of . mg/dl. no large variations inside the lot. medium level of serum creatinine . mg/dl; higher values in child c cirrhosis and hcc. conclusions: most of the metabolic disturbancies in hcc are correlated with the underlying liver disease. in a few cases of small lesions but mostly in large and complicated hcc these are significant and require specific treatment. background: a significant inter-individual variability in statin treatment efficacy is likely to have a strong genetic background. gene for slco b belongs to the candidates with potential to influence the statin treatment efficacy. slco b codes for solute carrier organic anion transporter, which has been shown to regulate the hepatic uptake of statins and some other drugs. materials and methods: slco b rs (t>c) polymorphism was successfully analysed in the group of patients with dyslipidemia (treated with simvastin or atorvastatin, or mg per day) and healthy normolipidemic controls. the polymorphism was analysed using nested pcr-rflp. lipid values (total-, ldl-and hdl-cholesterol, triglycerides) were analysed before and after - weeks of treatment. results: after treatment, as expected, there was a significant decrease both in total ( . self-care management), were applied to all patients at baseline and month follow-up. t-test and chi-square test were used to analyze the data. after months, (out of ) and (out of ) patients remained in the study. main findings revealed, a significant difference in a c level between the groups (p < . ). the self-care management score increased in both groups, but the increase was significantly higher in the intervention group (p < . methods: after the treatment decision was final, patients were assigned to either vildagliptin or other oads (sulphonylurea, thiazolidinedione, glinide, a-glucosidase inhibitor or metformin except dipeptidyl peptidase- inhibitor or glucagon-like peptide- mimetic/ analogue). demographic data and patient history, especially risk factors and macro-and microvascular complications, were collected and reported by the investigators. results: in total, , patients were enrolled in countries across the world. baseline characteristics are presented in the table. hba c was better controlled in east asia and europe than in india, latin america or middle east. patients in europe had higher bmi and longer duration of diabetes than patients in east asia and india. prevalence of risk factors such as hypertension and lipid disorders was high overall, but particularly higher in europe. macro-and microvascular complications were reported in . % and . % of the overall study population, respectively, and their prevalence was higher in europe. conclusions: data from edge study show that the hba c goal of % as recommended by international guidelines is not achieved worldwide and metabolic control varies remarkably between regions. in addition to the high prevalence of concomitant risk factors, complications were reported already after years of diabetes in a substantial proportion of patients. aim: sudomotor dysfunction due to small fiber neuropathy can be observed very early in pre-diabetes. the aim of this study was to assess the predictive power of ezscan, a non invasive, quick and simple measurement of sudomotor function to identify glucose impairment. research design and methods: the study was performed in german subjects at risk of diabetes. glucose metabolism was assessed by using, oral glucose tolerance test (ogtt) at baseline and after year follow-up. sudomotor function was evaluated by measuring hand and foot electrochemical sweat conductances to calculate a risk score. results: at baseline, patients had normal glucose tolerance (ngt), had pre-diabetes (impaired fasting glucose, ifg and/or impaired glucose tolerance, igt) and four had newly diagnosed type diabetes. the auc values for fpg, h-ogtt glucose, h-ogtt glucose, hba c and ezscan score to predict pre-diabetes were . , . , . , . and . respectively. subjects having a moderate or high ezscan score (> ) at baseline had a substantially increased risk for having ifg and/or igt at follow-up visit presented by an odds ratio of . [ . - . ], the or for having h-ogtt ! . mmol/l at follow-up was . [ . - . ] and for having hba c ! . % was . [ . - . ] compared to subjects with low ezscan risk. conclusions: this preliminary study, which must be confirmed in a larger population, shows that ezscan measurement is associated with diabetes progression which may have implications for prevention and disease management. methods: two groups are involved to the studies -the group of patients with metabolic syndrome (ms) and control group (c)- healthy, age matched volunteers. volunteers were expose to -h ogtt (according to who) and -h oltt (contained g of fat: % saturated, % monounsaturated and % pufa). during both tests the blood glp- , gip, glucose, insulin and free fatty acids (ffa) levels were assessed. results: fasting level of incretins do not statistically differ between ms vs. c participants. only ffas were elevated during whole oltt, when the glucose concentrations decreased in early postprandial period. secretion of gip was activated by ogtt as well as by oltt, however concentration of gip in oltt was higher. output of glp- during whole ogtt was significantly lower in patients with ms. in patients with ms amount of gip released during oltt was lower compared to control patients. conclusion: low level of incretins during oxidative stress connected with fat food intake, may not provide the protective effect for metabolically stressed pancreatic beta-cells. background: who estimates that . million deaths worldwide are due to hypertension, approximately . % of all deaths. this is an important risk factor forcardiovascular disease. argane oil is an integral part of the moroccan diet. several studies showed that an argane oil supplemented diet decreased systolic and diastolic blood pressure measurments in animals and suggested that consumption of argan oil may have a beneficial effect in preventing cardiovascular disease. objective: to study the effect of a regular consumption of argane oil on hypertension in healthy postmenopausal women. methods: seventy-seven postmenopausal women ( . ae . years) were assigned to consume ml of argane oil during weeks of nutritional intervention. anthropometric (weight, height and bmi) and clinical profile (blood pressure) have been determined at and weeks. results: showed that systolic blood pressure was significantly reduced ( . ae . to . ae . mmhg) after weeks (p = . ). diastolic blood pressure underwent a slight decrease ( . ae . to . ae . mmhg) but not significantly (p = . ). conclusion and perspective: these results suggest that consumption of argane oil can be relevant to prevent cardiovascular disease into postmenopausal women and help to decrease cardiovascular risk. the positive impact on blood pressure recorded by a significant decrease in sbp and hypertension is a significant result, however, the mechanisms involved in obtaining this result need to be defined more accurately, focusing mainly on the effects of certain constituents of argane oil as gamma-tocopherol on the mechanisms regulating blood pressure. the epidemic of obesity is associated with multiplication of prediabetic patients. recognition of them is essential as this state is considered to be the last chance to prevent the manifestation of diabetes. our aim was to determine metabolic alterations in healthy men with (dr: n = ) or without (h: n = ) first degree dm relatives. volunteers were adjusted according to age and bmi, insulin resistance was determined with hyperinsulinaemic-normoglycemic clamps and ßsejt function by iv glucose tolerance test. fasting glucose, insulin and ffa values were not different among the groups, but at the and of ivgtt, glucose levels were higher (h: . ae . , vs. dr: . ae . mmol/l, p < . ), injected glucose did not suppressed ffa levels (h: . ae . vs. dr: . ae . mmol/l, p < . ) and first phase insulin secretion was decreased in dr group (h: ae vs. dr: ae ; p < . ). there were no differences among the groups in total body-, muscle and fat tissue glucose disposal, leptin and resistin levels, but the adiponectin levels were significantly lower in dr group (h: . ae . vs. gd: . ae . mg/ml, p < . ) and the ffa/adiponectin ratios were higher (h: . ae . vs. gd: . ae . , p < . ). in conclusion the impairment of insulin secretion and fatty acid metabolism are the earliest sign of diabetes risk in men with first degree dm relatives. the measurement of ffa/ adiponectin ratio could be a simple parameter to screen adult male relatives of diabetic patients for identification of genetic risk of diabetes. the original reaven′s definition from , which has been revised in , missed the abdominal obesity. the definition accepted by who in was not applied due to difficult evidence of the insulin resistance. a new definition of the ms formulated by idf and ead was published in . in this case, the abdominal obesity was the necessary condition of the ms diagnosis. in order to unify the criteria, five essential parameters of the ms were put on the same level by the international medical organizations in . it is not easy to define the ms. it cannot be identified as a single disease, as it consists of a complex of problems. that is why the definitions of the ms were rearranged several times during past years and the used parameters are much stricter. we can assume that in the future this process will proceed. aims: the metabolic syndrome (ms) represents an obesity-related severe health problem, and its prevalence is world-wide increasing in parallel with the growing obesity epidemiology. gwa studies have shown that many single nucleotide polymorphisms (snps) in several genes are involved in common obesity. the aim of this study was to look for associations between snps in the mc r (rs , rs , rs ), sirt (rs , rs , rs , rs , rs ) and fto (rs , rs , rs , rs ) genes and obesity and/or ms in a southern italy population. methods: one-thousand unrelated non diabetic severely obese patients (mean bmi . kg/m , mean age . years) and controls (mean bmi . kg/m , mean age . years) entered the study. mc r, sirt and fto were genotyped by real time taqman assay. anthropometric, clinical and biochemical data were collected for all enrolled subjects. ms was diagnosed according to the american heart association criteria. results: metabolic syndrome was diagnosed in . % of our patients. the four fto snps were significantly associated with the obese phenotype ( . < p < . ). at binomial logistic regression analysis, only snp rs was significantly associated to obesity after correction for sex and age (or/ %ci: . / . - . and . / . - . , for the heterozygous and the homozygous mutated genotypes, respectively) and to ms presence (or/ %ci: . / . - . ) . conclusions: this study confirms that fto is a susceptible gene for obesity risk, and patients bearing the polymorphic allele in the rs snp could be at high risk of ms insurgence, possibly to be addressed toward preventive programs. results: number of patients who achieved hba c goals according age and presence of cvd are shown in table . conclusion: t d patient of middle age reached hba c goals in lowest percentage of cases. among different treatment groups percentage of patients reached hba c goals were the lowest in group treated by insulin with oad. the prevalence of diseases arising mainly due to the bad lifestyle is increasing. it is necessary to find optimal tools to lower the prevalence of the metabolic syndrome (ms). there is no network of institutions that systematically cooperate in the field of education and treatment of the ms. for students and academics the possibility of establishing ( ) and deepening the cooperation in this scientific field is therefore limited. the role of the project is to strengthen relations between the institutions in the form of cooperating network, which will meet the essentials principles of the primary, secondary and tertiary prevention of the metabolic syndrome. the key role of the project is to open an professional discussion and deepen the communication and professional relationship across the cooperating institutions which are realized primarily through internships of students (bachelor and doctoral degree), academic staff, roundtable discussions with experts and partners from the collaborating institutions, organizing workshops and doctoral and scientific conferences. czech society of sports medicine ( cstl) is a professional guarantor of creating a network of cooperating institutions in terms of the objectives and scientific credibility. background and aims: tissue ages accumulation is thought to be a specific marker of long-term glycaemic control, oxidative stress and cardiovascular risk. prediabetes -impaired fasting glucose (ifg) and impaired glucose tolerance (igt), are considered as risk categories for the development of both type diabetes and cardiovascular disease. the aim of the present study was to assess advanced glycation end products (ages) in prediabetes and their relation to anthropometric and glycaemic control parameters. material and methods: subjects (mean age . ae . years, mean bmi . ae . kg/m ) were enrolled. according to glucose tolerance they were divided into two age-matched groups - subjects with ngt and with prediabetes (ifg and igt). glucose tolerance was studied during ogtt applying who criteria. plasma glucose was measured by a hexokinase method, hba c was assessed immuno-turbidimetricaly. tissue ages accumulation was assessed non-invasively measuring the skin fluorescence of ultraviolet light on the ventral side of the lower arm (age-reader-diagnopticstm). antropomethric measurements -weight, height, waist circumference, were performed. visceral fat area was estimated by bioimpedance method (inbody ). results: no significant difference in ages accumulation was found between the groups with prediabetes and ngt. significant positive correlation was observed between ages accumulation, age (r = . ) and visceral fat area (r = . ). the non-invasive assessment of tissue ages accumulation probably is not a sensitive enough method for identifying subjects with prediabetes and increased cardiovascular risk. at the early stages of glucose homeostasis impairment ages accumulation appears to be related to age and visceral obesity rather than to glucose tolerance. this study is an observation study for mild diabetic males with bmi of or higher with subsequent month-follow-up based on single administration of exenatide and dietary and exercise intervention. method: subjects were cases of male patients (age: . ae . , bmi ae . ) with apnea hypopnea index (ahi)≧ /hr and . >hba c> . %. based on polysomnography and measurements of ct abdominal visceral fat area and various biomarkers before and and months after exenatide administration, the observation study was conducted for months. results: decrease in bodyweight was observed by . ae . kg on average during the months with no cases to gain in bodyweight and bmi. ahi was significantly improved from . ae . /h to . ae . /h. improvement was observed in hba c, -ohdg, pro-bnp, high molecular weight adiponectin and visceral fat areas but not in hs-crp and subcutaneous fat area. conclusion: not only diabetes but also sleep apnea syndrome was improved by exenatide administration in japanese mild diabetes patient. weight reduction may have played the primary role. effect of weight reduction provided by the pharmacological property of exenatide is useful to improve sleep apnea syndrome. currently, changes in individual calorie intake and nutrient composition during the study period have been analyzed. [ . - . ], p = . in igt group. no significant association was found between baseline fasting insulin level and progression from either ifg or igt to type diabetes. conclusions: individuals with ifg or igt identified through high-risk strategies in a bulgarian population, have a rather high risk of developing diabetes within year. baseline proinsulin and proinsulin: insulin ratio, known to reflect beta-cell dysfunction, appear to be independent predictors for progression to diabetes in both ifg and igt. introduction: the insulin receptor substrate (irs- ) seems to be an important factor involved in the modulation of insulin signalling in adipose tissue. in this study we want to check the expression of irs- in visceral and subcutaneous adipose tissue, its relationship with insulin resistance and with the metabolic syndrome. material and methods: we measured irs- expression in visceral and subcutaneous adipose tissue from morbidly obese patients. we have determined the level of insulin resistance with the homa-ir index. patients were classified into two groups based on whether or not to have metabolic syndrome (according to the idf criteria) results: irs- expression in subcutaneous adipose tissue is significantly higher than in visceral adipose tissue (p = . ). homa-ir was significantly correlated with the irs- expression in subcutaneous adipose tissue (r = À . , p = . ), but not in visceral adipose tissue (p = . , p = . ). the morbidly obese patients with metabolic syndrome have significantly lower irs- expression levels in subcutaneous adipose tissue than those without metabolic syndrome (p = . ). in visceral adipose tissue, the levels of irs- are lower but not significant (p = . ) in the morbidly obese patients with metabolic syndrome. the presence of metabolic syndrome in morbidly obese patients is associated with a lower irs- expression level in subcutaneous adipose tissue. in the general population and in hiv+ subjects the hypertension is the major risk factor worldwide for cardiovascular morbidity and mortality. this condition has been accompanied by several complication, including dyslipidemia and impaired glucose metabolism. for all these reasons identification of hypertension is of pivotal importance in hiv infected patients. aim of this study was to evaluate the incidence of hypertension and comorbidity in male hiv+ patients. we enrolled only male patients attending two clinics of the infectious diseases in center of italy (chieti and ancona). three hundred and four patients accepted to participate at the study. viroimmunological, lipid and metabolic parameters, including triglycerides, cholesterol, hcv/hbv co-infection, tabacco use were measured at the time of enrollment. the study has shown an incidence of hypertension (esh guidelines) % ( / patients), dyslipidemia % ( / ), diabetes % ( / ), hcv or hbv co-infection % ( / ) and tobacco use % ( / ). patients with hypertension showed dyslipidemia in % of cases ( / )and diabetes in % ( / ). remarkable that only % of patients with hypertension were treated for hypertension. in addition, the average age of the patients in the study was . ae . years. the study has shown a high incidence of hypertension in hiv+ men, even considering the young age of the patients. furthermore, hypertension is associated with a high incidence of co-mobility. hypertension is associated with evidence of under treatment, it showing a poor perception of the problem in this context. method: this study was a -weeks', prospective trial in subjects with metabolic syndrome. metabolic syndrome was defined as the presence of at least three out of five risk factors according to the ncep-atp iii with the asian criteria of abdominal obesity (abdominal circumference; > cm in men, > cm in women). all participants received individualized education by skilled personnel with information about tlc. blood chemistry including lipoprotein profiles and anthropometric data were collected before and after weeks' tlc. result: eighty-six subjects were screened, and subjects with metabolic syndrome were enrolled. body weight was not significantly changed after tlc. fasting blood glucose levels were not significantly changed (from . ae . to . ae . mg/dl, p = ns). therapeutic lifestyle change did not result in significant changes in total cholesterol (from . ae . to . ae . mg/dl, p = ns) and triglyceride (from . ae . to . ae . mg/dl, p = ns). but, weeks' tlc resulted in significant reduction in ldl-cholesterol levels (from . ae . to . ae . mg/dl, p < . ), increase of hdl cholesterol levels (from . ae . to . ae . mg/dl, p = . ). conclusion: four weeks' therapeutic lifestyle change improved lipoprotein profile (especially ldl-c and hdl-c) in metabolic syndrome. our findings indicate that the importance of tlc with education should be emphasized for the control of metabolic syndrome. nutrition, hasanuddin university, school of medicine, makassar, indonesia obesity in major public health and economic problem of global significance. the prevalence of obesity in children has increased significantly, although less rapidly in indonesia. from the public health view, it is disconcerting that the prevalence of adolescent obesity has increased by nearly % in the past two decade. case and control study design was done in makassar, the participant is senior high school students. the study aim to identify the risk factors of adolescent obesity to premetabolic syndrome by measuring body mass index, waist circumference, lipid profile (cholesterol, trigliceride, hdl, ldl and apo b) and fasting oral glucose. data was analyzed using spss program, the relationship among variables was calculated with pearson correlation and regression test. the indicators for obesity using waist circumferences and bmi, energy intake using h food recall and was analysed using wfood . the study showed, a positive correlation between waist circumference and small density ldl, apo b, cholesterol (p < . , p < . , p < . ). student with abnormal waist circumference tend to have abnormal biochemical markers (or . , . , and . ) as a risk premetabolic factors conclusion: nutrition education and food balance diet should be given to adolescent obesity to prevent metabolic syndrome in later of life. l. mundbjerg , g.f. thomsen , r. holst , c. juhl department of endocrinology, department of occupational medicine, hospital of south western denmark, esbjerg, institute of regional health research, region of south denmark, odense, denmark introduction: severe obesity is associated with reduced worker productivity and chronic absence from work. gastric bypass surgery is the most effective treatment of severe obesity. the objective of this study was to measure employment status in danish gastric bypass patients before and after surgery. methods: the study is a nation-wide retrospective case-control register study. data were extracted from three sources: cases were identified in the danish national patient register according to the operational code for laparoscopic gastric bypass surgery and matched on a : basis with respect to age, gender and residence municipality with control subjects. the employment status was calculated from the danish national labour market authority's databasedatabase (dream) which includes information on all public transfer incomes. by linking the databases we achieved a valid measure of the amount of working days. results: the amount of working days was significantly lower in cases compared to controls. there was a significant decline in employment status during the observational period in both groups. this decline corresponded with the timing of the financial crisis (employment data collected over the period january st to december st ). there was no significant difference in the decrease of employment status between groups. conclusion: gastric bypass surgery patients are affected by the economic recession in a similar degree as the general population. thus, the patients do not seem to benefit from the operation nor do they appear particularly vulnerable in periods of recession. excessive accumulation of fatty tissue in obesity associated with fat and glucose metabolism. fish oil contains n- pufas epa and dha had been demonstrated in several studies had effects on the expression of genes ppar-a and srebp- c, the pathomechanism still controversial. this study aims to determine the effect of fish oil on insulin resistance in mice obesity. clinical trials using c bl/ j mice was conducted in animal laboratory medical faculty of hasanuddin university. the mice was giving a normal diet (nd) or high fat diet (hfd) for weeks. mice was divided by four groups; normal diet (nd), high-fat diet (hfd), hfd + g/ g fish oil (hfd-fo), hfd + metformin g/kg diet (hfd-met) as a positive control for weeks. gene expression of ppar-a and srebp- c from the liver were measured by rt-pcr. the study showed, hfd mice had significantly higher body weight compared to nd. hfd-fo have higher blood glucose levels than other groups. ppar-a expression in liver was lower in hfd than nd, but increased in the hfd-fo and hfd-met compared with hfd alone. srebp- c expression decreased in hfd-fo and hfd-met, glucose metabolism of hfd_fo tended to decrease, while the hfd-met is likely to increase. we conclude, fish oil improved insulin resistance, decreased expression of srebp- c and increased expression of ppar-a in the liver tissue through decreasing lipogenesis and increased fat oxidation in the liver. methods: total subjects were divided into two groups having whr > . as obese and whr < . as non-obese. circulating il- and resistin level, fasting blood glucose, insulin and lipid profile were estimated. insulin resistance was calculated by the homeostasis model assessment (homa) index. the genotype and allele frequency of il -g c gene polymorphism was determined by pcr-rflp method in obese and non-obese adult women from north india. results: the genotype distribution of il -g c gene polymorphism was statistically significant in obese women (p = < . ; or = . ; % ci = . - . ) compared to non-obese women. the circulating level of serum resistin was highly significant in obese women ( . ae . vs. . ae . , p = < . ) compared to nonobese. significant association was found with cc + gc genotype of il -g c promoter gene polymorphism in case of waist circumstance, serum triglyceride, homa index and serum resistin level (p = . ; or = . , % ci = . - . ). conclusion: serum resistin is associated with the disorder of metabolism of glucose and lipid in metabolic syndrome. the relationship between this hormone with cc + gc genotype of il -g c promoter gene polymorphism suggests that they may take part in the development of metabolic syndrome in north indian adult women. the comorbidities associated with excessive weight are major causes of morbidity and mortality, thus causing further reduction in quality of life. the dysfunction of excessive fat and its peculiar distribution plays a decisive role in the development of metabolic disorders. the aim of the study was to estimate the prevalence and the correlates of obesity and dysglycemia in a rural community. overweight and obesity were defined according to world health organization criteria, considering both the value of body mass index (bmi) and waist circumference (wc). dysglycemia (impaired fasting glucose -ifg and diabetes) was established based on ada recommendations. the study included people, . % men and . % women, with the mean age of . ae . years. more than half of them ( %) had an excessive weight: . % were overweight and . % were obese. the crude prevalence of overweight and obesity was . % and . % respectively for men, and % and . % respectively for women. the prevalence of diabetes was . % and for ifg of %. the prevalence of dysglycemia increased with the bmi value, with the highest frequency in the grade iii obesity group ( . % prevalence of diabetes, ifg . %). large wc was identified in . % of the studied population ( . % in men, . % women). the individuals with diabetes had a significant higher mean wc ( . cm vs. . cm, p < . ). these results show that excessive weight and abdominal obesity could become a public health problem in romania, thus requiring national screening and educational programs. objective: hyperuricemia is associated with obesity; however, few studies reported the effects of surgery types on uric acid metabolism for severe obesity. the current study was aimed to explore the effects of gene and bariatric surgery on uric acid reduction and to identify the potential pathways. subjects: all participants were han chinese, aged from to years old. a total of severely obese patients with at least body mass index (bmi) of were recruited in the beginning of the study, where cases received laparoscopic adjustable gastric banding (lagb) and cases received laparoscopic mini-gastric bypass (lmgb). a -month follow-up was ensued after surgery to identify the effects of bariatric surgery and estrogen receptor-a (esr ) gene on serum uric acid reduction. results: a tagsnp (rs ) of esr could influence serum uric acid reduction. bariatric surgery effect on serum uric acid reduction was greater in lmgb as compared with lagb at the th month of post-surgery (À . ae . mg/dl vs. À . ae . mg/dl, p = . ). obese patients carrying risk genotype (tt) on rs and exhibiting better glycemic control had a greater serum uric acid reduction at the th month of post-surgery. synergic effect of rs and lmgb exhibited the highest serum uric acid reduction at the th month of post-surgery (À . ae . mg/dl). conclusion: for severely obese han chinese, bariatric surgery appears to reduce serum uric acid levels by mediating different factors, including esr gene and gender, ameliorating glycemic control, and changing dietary patterns. remained significantly lower. compared to mgc, mgr but not mgrc male offspring had higher body fat % and visceral adiposity at months of age. results: the average age of patients was . years, more dominant were females with . %. patients with ms characterizes increased values of bmi ( . kg/m²), which is statistically significantly more that in the control group, where is average value of bmi . kg/m², waist . cm in the study group, and . cm within control group (p < . ), blood pressure . / . mmhg, homa index . , average value of insulinemia . (lu/ml), (within control group homa index was . ), the average value of insulimenia . (lu/ml), average values of: total cholesterol . mmol/l, hdl cholesterol . mmol/l, ldl cholesterol . mmol/l, triglycerides . mmol/l, relation between ldl/hdl . . arterial hypertension was present in . %, hypercholesterolemia in . %, reduced hdl in . %, increased ldl in . %, trigliceridemia in . %. conclusion: abdominal obesity is characterized by manifested insulin resistance and distinct hyperinsulinemia. arterial hypertension as one of the components of metabolic syndrome represents significant cardiovascular risk factor, increased level of triglycerides represents significant risk factor which favors atherosclerosis, in our study the presence of this parameter was . %. introduction: diabetes is the most feared disease because it leads to a variety of complications including end-stage vascular disease, cardiovascular damage and retinal abnormalities. the increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. cardiovascular disease (cvd) is the most prevalent complication of diabetes mellitus. methods: the aim of this study was to assess the ldl susceptibility to lipid peroxidation (ldl ox) in two study groups of elderly patients (aged ae years): a group of patients with cardiovascular disease and a group of patient with cardiovascular disease associated with type diabetes mellitus. the ldl susceptibility to in vitro induced lipid peroxidation was evaluated following its incubation with a prooxidant system. : results obtained showed the susceptibility of ldl to in vitro oxidation was increase in diabetic group ( . %) compared with a cardiovascular disease group. conclusion: this study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. patients with diabetes have a greatly increased relative risk of developing cardiovascular disease when compared with patients without diabetes. much of this risk is related to insulin resistance and is associated with both traditional and nontraditional cardiovascular risk factors. therefore, measurement of ldlox may be helpful for identifying high-risk patients with type diabetes and cvd. janus kinase (jak) and signal transducer and activator of transcription- (stat ) in several cell lines. objective: we sought to determine the role of hypothalamic s pr in the control of jak /stat signaling and food intake in vivo. materials and methods: western blot, immunohistochemistry, gas analyzer, dissection of the hypothalamic nuclei and intrecerebroventricular (icv) infusion of s p ( ng), leptin ( À ) and cucurbitacin ( lmol/l) were combined to evaluate the role of s pr on leptin signaling and on food intake in lean and obese wistar rats and in ob/ob mice. results: high expression of s pr was found in the hypothalamus when compared to other peripheral tissues. s pr is mainly expressed the arcuate nucleus of the hypothalamus, in the same neurons that possess stat . icv infusion of s pr activator, s p, increased jak and stat phosphorylation and the energy expenditure and reduced the food intake in lean rats. in addition, s p potentiated the effects of leptin in the reduction of food intake. conversely, the pharmacological inhibition of stat , blocked the anorectic effect of s p. interestingly, low expression of s pr was observed in the hypothalamus of ob/ob mice and wistar rats fed on high fat diet, whereas, s p infusion reduced the food consumption and increased leptin signaling and action in obese rats. these results indicate that hypothalamic s pr has a key role in the control of leptin signaling and on food intake. aim: the adifit program is an intensive -week multidisciplinary treatment program which promotes weight reduction among obese. during the first weeks behavior change, physical exercise, and nutritional counseling is offered three times a half a day per week, thereafter once a week half a day. the aim was to evaluate efficacy of the adifit program in weight reduction, and its effect on eating behavior, and body image. methods: patients were evaluated at baseline (t ) and after month (t ). bmi was assessed. psychometric instruments such as the german versions of the eating behavior questionnaire (fev), and the body image questionnaire were used at both time points. paired-sample t-test and wilcoxon signed rank test were used for statistical analyses. results: fifty patients participated, % were female. bmi was significantly reduced from t to t (mean ae sd: . ae . vs. . ae . ; t = . , p < . ). results discerned significant improvements from t to t in fkb scale (negative attitudes towards one′s own body) ( . ae . vs. . ae . ; t = À . , p < . ), and scale (restricted body dynamics) ( . ae . vs. . ae . ; t = À . , p < . ). on the other hand, fev scale (cognitive restraint of eating) improved significantly from t to t ( vs. , z = À . , r = À . , p < . ). fev scale (disinhibition) was significantly lower at t ( vs. , z = À . , r = À . , p < . ) as was fev scale (hunger) ( vs. ; z = À . , r = À . , p < . ). after weeks patients showed significant reduction in weight, improvements in body image and eating behavior. metabolic peptides in serum and plasma samples contain status information for diabetes. previously, we have demonstrated that intrinsic protease activity caused instability of plasma and serum peptides. other reports have described that metabolic peptides, including glp- , gip, glucagon, and oxytomodulin, are subject to instability caused by proteolytic and other enzymatic degradation intrinsic to plasma. the variability may result in inaccurate quantitative measurements of the peptides creating challenges when interpreting pharmacokinetic and pharmacodynamic data. using both mass spectrometry and elisa based detection methods; we investigated the instability of metabolic peptides in whole blood, serum, and plasma under a variety of routine clinic conditions. first, the same subjects blood was drawn into different blood collection devices including serum and edta, citrate, heparin, and an edta tube containing enzyme inhibitors. the metabolic peptides of interest were spiked into plasma for time incubation at different temperatures. samples were quenched and processed for both maldi-tof ms and elisa analyses. quantitative analysis of each marker was used to characterize the kinetics of the peptide digestion ie stability (halflife). further a blood collection tube was developed to minimize degradation using enzymatic inhibitors specifically for the stabilization of glp- , gip, glucagon, and oxytomodulin. the addition of specific enzyme inhibitors for stabilization of each peptide reveals more insight regarding enzymatic degradation and stabilization of the peptide biomarkers. our data clearly demonstrates the need of enzymatic inhibitors for peptide stabilization, especially in a clinical setting. ( . ae . mg/dl) . subjects underwent a standardized meal test: g of bread, a boiled egg, g of apple, in the morning after h fasting. venous blood glucose samples:before meal test (sample ), h (sample )and h (sample ) after ingestion of standardized meal. neuropathy (p = . ). women had higher prevalence of neuropathy (p = . ). people with sensory neuropathy had lower weight and bmi than those with autonomic neuropathy and those without neuropathy (p = . ). fasting blood glucose was higher in subjects with neuropathy (p = . ). value of sample was increased in people with neuropathy (p = . ). other parameters cardiometabolic risk factors were not associated with diabetic neuropathy at onset of t d. conclusions: diabetic neuropathy is a frequent complication at diagnosis of t d. people with higher fasting or postprandial glycemia may associate more frequently diabetic neuropathy at onset. m. metalla , m. carcani , g. qirjako , e. demiraj durre regional hospital, endocrinology, durre regional hospital, durres, statistical, mother teresa university hospital center, tirana, internist, durre regional hospital, durres, albania background: metabolic syndrome is a risk factor for cardiovascular diseases and is associated with abnormal cardiac structure and function. the aim of the study: to evaluate the left ventricular structure and function in patients with metabolic syndrome, without installation of diabetes mellitus or arterial hypertension. material and methods: it was analyzed a total of consecutive adults ( -{ %} males and -{ %} females) with metabolic syndrome and healthy ( -males and females) without metabolic syndrome. metabolic syndrome was defined using the atp lll criteria. assessment is done with classic echocardiography, pulsed wave doppler and tissue doppler. results: there was difference in two groups in bmi, in waist circumference, in systolic and diastolic arterial presure in total colesterol, in level of triglicerid and hdl colesterol p < . . there was no diference in age, fasting serum glucose level, lvedd, sw, pw, lvm, lvmi, lav, lvef, early trans mitral inflow (e), late trans mitral inflow (a) and in the rate e/a (p = . ). echokardiografic measurements by tdi in peak mitral anular velocity in early diastole ea were . ae . vs. . ae . cm/sec (p < . ) in the metabolic syndrome and controll grups respectively. average values of sa were significantly lower in the ms than in controll group, . ae . vs. . ae . (p < . ). the ratee/ea mitral was . ae . vs. . ae . (p < . ) in metabolic syndrome and controll group respectivly. the early identification of isolated syndrome in non diabetic, non hypertensive adults may be an indication of an aggressive preventive measure. the fasting glycaemia altered and hyperinsulinemia are strong predicting factors of type dm (dm ) and sedentary habits can lead to this disease, mainly associated with obesity. objectives: verify the influence of physical activity, vo max and anthropometric measurements on glycaemia and insulin fasting in active military over the age of of the brazilian army (ba) serving in rio de janeiro. methods: two hundred and fifty subjects (aged . ae . years), in active duty in the ba, volunteered to participate in the study. the insulin and glycemic levels were measured as well as body mass, stature and waist circumference. body fat (bf) was measured by hydrostatic weighing, when body density was obtained. vo max was measured by maximal cardiopulmonary treadmill exercise test (cpet) using an individualized ramp protocol. oxygen consumption and carbon dioxide production were measured using a cpx-d metabolic cart. results: the prevalence of type dm found was . % and afg was . %. vo max showed an inverse correlation (p < . ) with insulin levels, homa-ir and fasting glycaemia and also with anthropometric measures and %bf. the bmi and %bf presented direct correlation (p < . ) with insulin, homa-ir and fasting glycaemia. subjects in the highest quartiles of vo max and in the lowest quartiles of wc and of %gc also presented lower levels of fasting glycaemia and insulin and homa-ir. the data suggest that vo max was an inverse and nutritional state a direct relationship between glycaemia and fasting insulin. subjects with an active lifestyle have less prevalence of alterations in glycaemia and fasting insulin levels. the increase in prevalence of cardiovascular conditions, and metabolic syndrome (ms) observed in the last decades was accompanied by increase in dietary fructose (fr) consumption (also as sucrose). the aim was to assess the prevalence of fructosemia in cardiovascular patients with or without ms and to investigate the possibility of treatment of hyperfructosemia and other components of ms with oral acarbose. material and methods: fasting serum fr concentration in cardiovascular patients with metabolic syndrome (group ) and in cardiovascular patients without ms (group ) was measured by colorimetric method with commercially available biovision set. patients of the first group were treated with acarbose (glucobay, bayer) increasing the dose from to mg per day to normalize the glucose metabolism. fasting and post oral sucrose load ( g) serum levels of glucose, fr, insulin, nefas and uric acid (ua) were measured at baseline and in days. results: fasting serum fructose concentration varied widely and among patients in both groups, and was significantly higher in group ( . ae . vs. . ae . lmol/l). the data after days and weeks of acarbose use is presented in the conclusions: dyslipidaemia is found to be the risk factor for ischemic stroke in diabetic subjects, with statistically significant differences compared to nondiabetics. hdl-cholesterol was found as a protective factor for haemorhagic stroke in nondiabetic subjects. agave tequilana weber variety azul is an economically important in mexican people because it is the sole plant allowed for tequila production but because it is a potential source of prebiotics, the inulin-type agave are nondigestible/fermentable carbohydrates which are able through the modification of the gut microbiota, the pos content of agave inulin differs from inulin extracted from chicory root. the aim was to assess the efficacy and safety of inulin type agave on lipid profile in dyslipidemic obese subjects. a clinical trial, open was carried out in obese, hypertrygliceridemic and hypercholesterolemic subjects between and years old. all the subjects received g/day of inulin in the morning, during days. biochemical and metabolic profiles before and after pharmacological intervention were performed. after inulin administration, there was a significant reduction of the trygliceride concentrations ( . ae . and . ae . mg/dl; p = . ). glucose serum ( . ae . and . ae . mg/dl; p = . ), and hba c ( . ae . and . ae . % p = . ). there was not a significant reduction of total cholesterol, low density lipoprotein and very low density lipoprotein. anthropometric parameters did not change in the group and soluble fiber intake did not produce any gastrointestinal adverse effect. the increase of fiber intake (inulin type agave) are efficacy and safety to reduced trygliceride concentrations levels in dyslipidemic obese patients. stress and strain have long been associated with the work people do. we aimed to investigate occupational stress index and influence of several different work stressors on cardiometabolic risk factors: diabetes, lipid levels in hypertensive workers in south serbia methods: we studied persons (professional drivers, construction workers, production line workers and bankers): composed group with hypertension ( - years of age, majority males), were age and sex matched controls without hypertension. clinical examination was performed and blood was sampled. we analyzed work stressors by using questioners with different factors and occupational stress index (osi) was calculated with permission of dr belkic. comparison was made regarding total burden and the nature stress burden (underload, high demand, strictness, extrinsic time pressure, aversive/noxious exposures, threat-avoidant vigilance/disaster potential, conflict/uncertainty) results: diabetes was highly present in bankers ( %) and glucose levels were significantly higher in this subgroup. the incidence of diabetes in construction workers was %. total cholesterol, ldl, triglycerides were higher and hdl lower in bankers and contraction workers (p < . ) and linearly correlated with osi (p < . ). previous myocardial infarction suffered . % of bankers. total osi was significantly higher in diabetic hypertensive bankers and construction workers (p < . ), as well as high demand, strictness and extrinsic time pressure (p < . ). conclusion: hypertension appearance in working population is related to high osi, especially when other cardiometabolic risk factors added. further steps are needed to reduce the level of work stressor and provide a better quality of live in individuals. background and aim: plasma levels of adipocytokines in healthy individuals or diabetes mellitus patients have been previously reported as well as salivary levels of many adipocytokines. nevertheless, salivary levels of some adipocytokines in patients with metabolic syndrome have not been investigated. the aim of this study was to evaluate salivary and plasma levels of leptin and adiponectin in patients with metabolic syndrome. results: compared with healthy individuals, leptin levels in patients with metabolic syndrome were significantly increased, both in plasma ( . ae . vs. . ae . ng/ml, p < . ) and in saliva ( . ae . vs. . ae . pg/ml, p = . ). whereas plasma adiponectin levels were decreased significantly in patients with metabolic syndrome ( . ae . vs. . ae . lg/ml, p = . ), salivary adiponectin levels were inversely increased ( . ae . vs. . ae . ng/ml, p = . ). conclusion: this study showed that, similarly to plasma, there was an elevated change in salivary leptin levels in patients with metabolic syndrome compared to healthy individuals. however, for salivary adiponectin levels, the opposite result to plasma adiponectin levels was revealed. replacing saliva to plasma for detecting altered leptin and adiponectin should be concerned in patients with metabolic syndrome. objective: to examine dietary intake in family members with diabetes type (dt ) to identify contributing factors to glycemic control and development dt . design: descriptive and prospective study involving members of families who provided food intake from days, weeks days and weekend day. inclusion criteria were proband member diagnosed with dm with ! siblings and living parents. methods: data were collected at the participants' homes or at the university clinic. the biometric measures were glucose and hemoglobin glucose (hba c). data was entered into nutritional data system to research, the "gold standard" for nutritional analysis. also, the data entry into spss v was done. : of , ( % women, mean age . ae . ; , mean blood glucose . mg/dl ae . ; - and mean (hba c) . % ae . ; . preliminary data indicate intake total fat was higher than the recommendations % of participants, while carbohydrate intake was higher in %. method: this was a retrospective, observational study of consecutive cardiac bypass patients that underwent surgery at sultan qaboos univesity hospital in muscat, oman, between and . analyses were performed using descriptive statistics. the study included a total of cardiac bypass surgery patients with an overall mean age of ae years and % ( / ) were males. mean body mass index was kg/m ranging from to kg/m . twenty-seven percent of the patients were either past or current smokers while % ( / ) had a family history of coronary artery disease. all but of the patients ( %) were on statins pre-op. the most prominent co-morbidities were hypertension ( %), angina ( %), diabetes mellitus ( %), myocardial infarction ( %), and congestive heart failure ( %). the mean average pre-op total cholesterol, low-density lipoprotein cholesterol (ldl-c), high-density lipoprotein cholesterol (hdl-c), triglycerides, apolipoprotein a (apo a ), and apolipoprotein b (apo b) were . ae . mmol/l, . ae . mmol/l, . ae . mmol/l, . ae . mmol/l, . ae . g/l, and . ae . g/l, respectively. eighty-one percent, %, and % of the patients had or or diseased heart vessels, respectively. there was a total of %, %, and % of the patients that had on-pump, off-pump, and on-pump beating coronary artery bypass surgeries, respectively. mortality was recorded in two patients ( %) in an approximately -year period. conclusions: patients undergoing cardiac bypass surgery were observed with a high prevalence of cardio-metabolic risk factors. aim: to evaluate the association between osteocalcin and phenotypic characteristics of metabolic syndrome. material and methods: data of children and adolescents participants of the project "health worker cohort study" was analyzed. to each participant we determined: insulin, glucose, triglycerides, hdl, waist circumference and blood pressure. glucose and insulin were evaluated by glucose-oxidase method and homa. total osteocalcin concentration was determined by chemiluminescence. body mass index (bmi) was evaluated according to cdc chart′s for children and adolescents according to age and sex. using multiple lineal regression and logistic regression we evaluated the association between osteocalcin values and components of metabolic syndrome. results: the proportion of male in the study population was . %. the prevalence of overweigh and obesity was . % and abdominal obesity was . %. the proportion of elevated glucose, hypertriglyceridemia, low levels of hdl, hypertension and metabolic syndrome were . %, . %, . %, . % and . % respectively. difference of medians according to ages groups, was observed for glucose, insulin, homa and osteocalcin (p < . ). the study showed a negative correlation between bmi, fat percentage, waist circumference, glucose levels and crp with ostelcalcin levels (p < . ). conclusions: serum osteocalcin levels were associated with some phenotypic characteristics of metabolic syndrome and measures of adiposity. background: previous studies show that hyperuricemia precede the development of the metabolic syndrome and can be a risk factor to diabetes type , cardiovascular disease and heart failure, independently of obesity. aim: to identify the association between hyperuricemia and cardiovascular risk factors (crf). the study population included adolescents, all of them participants from the "cohort study of health workers". crf were evaluated according to idf pediatrics criteria. the cut-off points for hyperuricemia was levels of uric acid > mg/dl, for hyperinsulinemia > mu/l, insulin resistant (ir) have homa > . . a multivariate regression analyses was used to evaluate the association between hyperuricemia and crf. resultados: the proportion of female in the study population was %. mean age was ae . years, prevalence of bmi >p was %, abdominal obesity ( . %), hypertension ( . %), hyperuricemia ( . %), glucose ! ( . %), hypertrigliceridemia ( %), low levels of hdl ( %), hyperinsulinemia ( %), ir ( %), crp ( . %) and ms ( . %). proportion of hyperuricemia was six times higher in men, ( vs. . , p < . ). the study show association between hyperuricemia and age (or: . ;ic % . - . ), hypertrigliceridemia (or: . ;ic % . - . ) hyperglucemia (or: . ;ic % . - . ), hyperinsulinemia (or: . ;ic % . - . ), ir (or: . ;ic % . - . ), abdominal obesity (or: . ;ic % . - . ) and ms (or: . ;ic % . - . ). conclusions: hyperuricemia is associated to crf. hyperuricemia is not considered for adolescent health diagnostic. however early diagnostic is important for avoid the presence of several crf. method: pancreas of fetuses and offspring from diabetic and nondiabetic sprague-dawley rats were obtained and processed for histological and morphometric studies and for inmunohistochemical analysis of pdx. , insulin and glut . results: fetuses of diabetic mothers, showed a significant delay in the morphogenesis of the islets, with a significant reduction of the diameter, area and beta cell mass and expression of pdx , insulin and glut . these fetal alterations had an impact on postnatal life and offspring of diabetic rats had significantly higher glucose levels. in offspring of days, the alterations persisted and the expression of insulin and glut was significantly lower. at days the islets were mature but the size, beta cell mass and expression of insulin, glut and pdx. were still significantly lower. at days the structure of the islets was normal, but the reduction in size, beta cell mass and expression of glut persisted, but with no significant reduction in the expression of insulin and pdx. conclusions: in utero hyperglycemia induced a delay on the differentiation of beta cells and morphogenesis of islets, a reduction of the beta cell mass and in the expression of insulin, glut and pdx. . these alterations persisted up to adulthood causing hyperglycemia to offspring. g. yoshino , t. an , s. nakano , k. kuboki center for diabetes, shinsuma general hospital, kobe, division of diabetes, metabolism and endocrinology, department of internal medicine, toho university, tokyo, japan background and aim: it has been a matter of debate whether the intervention is necessary even for elderly metabolic syndrome subjects. present study is therefore conducted to explore whether the elderly subjects with metabolic syndrome show increased cad risk measuring plasma small, dense ldl-cholesterol, hs-crp and plaque score of the carotid artery. methods: a total of subjects including male ranging from to years-old, were recruited for this study. they are divided into four groups according to their age (below and above years-old) and an association of metabolic syndrome. blood sampling was done after overnight fast. small, dense ldl-cholesterol was measured employing direct assay method. results: in the non-elderly subjects, plasma triglyceride, small, dense ldl-c, hs-crp and plaque score of carotid artery were all increased in the metabolic syndrome group compared to that of non-metabolic group, while there was no significant difference in either hs-crp or the plaque score between the two groups within elderly subjects. within the elderly metabolic syndrome group, subgroup with type diabetes had higher fasting blood glucose, hs-crp, small, dense ldl-c and plaque score than the subgroup without type diabetes. conclusion: metabolic syndrome is an important factor for progression of subclinical atherosclerosis in the non-elderly subjects, but it cannot be a significant determinant of subclinical atherosclerosis if the subjects are limited within elderly group without type diabetes. thus, intervention for metabolic syndrome may not be obligatory for elderly metabolic syndrome subjects if they are not diabetic. methods: a retrospective cross-sectional study of randomly selected patients on antihypertensive drugs at the outpatient clinic at sultan qaboos university hospital, muscat, oman. the recorded variables included age, gender, history of diabetis mellitus, weight, fasting blood glucose, creatinine level, systolic blood pressures (sbp), diastolic blood pressure (dbp), and type of medication. all parameters were collected of the last two visits from (january and december ) for each patient who had been labeled with persistent hypertension using the hospital information system (his). analyses were conducted using descriptive statistics. results: overall mean age of the cohort was ae years, % were male, % were diabetic, mean sbp ae , dbp ae , weight ae , and fbg . ae . on visit , % were on b-blockers, % patients were on calcium channel blocker, % on angiotensinconverting enzyme inhibitor and % were on diuretics either as a monotherapy or in combination. target bp was attained in . % patients with diabetes mellitus compared to . % in non diabetics after the second visit. the mean body weight in patients with controlled hypertension was . kg compared to . kg in patients with uncontrolled hypertension. the study showed that diabetes mellitus, increased body weight and high fasting blood glucose reduces the attainment of blood pressure goal in patient on antihypertensive therapy. purpose: comparable evaluation of lipid profile and inflammatory markers between patients with stable angina (sa) and patients with sa and diabetes mellitus of type (dm). material and methods: a total of patients with sa (mean age . ae . years) with coronary stenosis < % were examined. group i included patients with sa and dm; group ii - patients with sa without dm. lipid profile parameters; inflammatory markers (hs-crp, tnf-alpha, homocysteine, interleukine β, , ; scd l, mmp- , timp- ); endothelial dysfunction markers (endothelin- , nitrites) were measured initially and in year. results: there were high levels of hs-crp, tnf-alpha, lipoprotein (a), mmp- , triglycerides, and endothelin- in both groups. the level of timp- reduced in both groups. patients in group had significantly elevated levels of total cholesterol, ldl cholesterol, homocysteine, apo-b, apo-b/apo a- ratio, il- β. in group the following positive correlations were found: between glycohemoglobin and apo-b, apo-b/apo a- ratio, homocysteine; il- and hs-crp; homocysteine and ldl cholesterol, mmp- , duration of coronary artery disease; endothelin- and scd l, tnf-alpha. reliable increasing homocysteine, tnf-alpha mmp- , ldl cholesterol were revealed in both groups. conclusions: prospective study showed that both groups had similar blood biochemical abnormalities. however in patients with dm there was an increase in the levels of atherogenic lipid fractions as well as homocysteine, tnf-alpha and mmp- which may indicate a higher risk of developing coronary events even in the absence of significant coronary stenosis. objectives: il- is a pleotropic cytokine and is reported to be involved in various inflammatory and immune-mediated disorders. previous data in apo e-/-mice demonstrated that il- accelerates atherosclerosis via ifn-c and cxcl expression and the effect was independent of t-cells. we therefore investigated whether il- is involved in cholesterol efflux and plaque stability. methods: two groups of chow-diet-fed, male apolipoprotein e-/mice, aged weeks (n = /group) were fed a normal diet and injected intraperitoneally for days with either recombinant il- ( ng/g/ day) or with phosphate buffer saline (pbs). mrna expression of il- , scavenger receptor cd , mmp- and lxr-a genes was determined by real-time pcr. immunohistochemistry was also performed for expression of above genes. results: il- administration led to a significant increase in serum cholesterol and lipoproteins except hdl-c which was decreased. in heart and aortic tissues, expression of il- , scavenger receptor cd and mmp- genes increased . , and fold respectively, whereas expression of lxr-a gene was reduced by . fold. atherosclerotic lesion size was quantified in the ascending aorta and the aortic arch. exogenous il- administration significantly increased frequency of atherosclerotic lesions and lesion area in il- treated mice vs. control animals ( . ae . % vs. . ae . % (p < . ; pbs vs. il- group). the observed data strongly implicates il- as a proatherogenic and proinflammatory molecule which not only enhances inflammation but augments cd and mmp- expression which may lead to enhanced foam cell formation and plaque instability and thereby aggravate atherosclerosis. objective: the present study was attempted to found the association between tnf-a promoter gene g- a polymorphism with metabolic syndrome and insulin resistance. the g- a tnf-a polymorphism has been studied in subject with metabolic syndrome according to ncep atp iii criteria (age . ae . ; bmi . ae . ) and healthy control without metabolic syndrome (age . ae . ; bmi . ae . ). the g- a variant was detected by pcr amplification and nco- digestion. furthermore insulin resistance, serum leptin and tnf-alpha levels were also measured in both the groups. polymorphism was significantly less frequently observed in the control population as compared to study group. furthermore, on dividing the subjects into two groups according to the absence (homozygous for the wild type g allele) (tnf- allele) or presence of the mutant a (tnf- ) allele, significantly high levels of tnf-a (p = . , or = . , % ci = . - . ) and leptin (p = . , or = . , %ci = . - . ) were observed in tnf- group as compared to tnf- group. whereas, there was a non-significant tendency toward insulin resistance in the tnf- group. conclusions: our results suggest that the g- a mutation of the tnf-a gene is likely to play an important role in the development of metabolic syndrome and metabolic abnormalities. metabolic syndrome is associated with residential-area crime rates for men and perceived crime for women: gender differences in social vulnerability to metabolic syndrome introduction: crime rates and perception of crime within neighbourhoods have been linked to residents' cardiometabolic outcomes. men and women vary in their perception of crime but share exposures to residential-area crime. it is unclear whether gender differences exist in the nature of crime-related vulnerability to metabolic syndrome. aim: to assess gender-specific associations between perceived and reported crime, and metabolic syndrome (mets) methods: cross-sectional data from a biomedical cohort study of adults randomly selected from the north-west region of adelaide, south australia, were analysed (n = . ) (mean age = . , standard deviation = . ). clinically measured mets was defined using international diabetes federation criteria. perceived crime was expressed as a standardised factor score reflecting six items related to neighbourhood safety and crime. reported crime rates were obtained from police data, aggregated at the statistical local area level (n = ) and standardised. associations were evaluated using multilevel regression models accounting for area-level clustering and covariates including area-level income and participant sociodemographic factors. results: the prevalence of mets was, for men (n = ), . % ( % ci = . - . ), and for women (n = ), . % ( %ci = . - . ). for men, mets was associated with rates of violent crime (or = . , %ci = . - . ) and total crime (or = . , % ci = . - . ), but not perceived crime. for women, mets was associated with perceived crime (or = . , %ci = . - . ), but not reported crime. conclusions: crime is an adverse social exposure. mets is associated with perceived crime in women and reported crime rates in men. these differentials suggest gender-specific causal pathways by which awareness and perception of adverse social exposures relate to mets independent of socioeconomic factors. background: epidemiological studies suggest that the resting heart rate (rhr) is an independent predictor of cardiovascular and all cause mortality. however, the power of the rhr to predict cardiovascular events in patients with the metabolic syndrome (mets) is not known. methods: we prospectively investigated the relationship between rhr and cardiovascular events in consecutive patients undergoing coronary angiography for the evaluation of coronary artery disease (cad) over a follow-up period of . ae . years. the mets was defined according to ncep-atpiii criteria. results: in the total study population, both all cause and cardiovascular mortality were increased with an increasing rhr (standardised adjusted hrs . [ . - . ]; p = . and . [ . - . ]; p = . , respectively). from our patients, ( . %) had the mets and did not have the mets. among patients without the mets, a higher baseline rhr indicated a significantly higher risk of total mortality (h = . [ - . ], p = . ) and cardiovascular mortality (hr = . [ . - . ], p = . ) after multivariate adjustment. however, the rhr did not significantly affect total mortality (p = . ) or cardiovascular mortality (p = . ) in patients with the mets. interaction terms rhrxmets were significant for both total and cardiovascular mortality (p = . and p = . , respectively), indicating that the respective risks conferred by a high rhr were significantly higher in patients without the mets than in patients with mets. conclusion: we conclude that among angiographically characterized coronary patients, the metabolic syndrome status significantly affects the association of the rhr with total and cardiovascular mortality: rhr is a strong predictor of both total and cardiovascular mortality among subjects without the mets, but not among mets patients. aim: to estimate influence of diet therapy, physiotherapeutic treatment to body mass reduction and prevention of cardiovascular and metabolic risks. patients and methods: were surveyed patients with a metabolic syndrome aged of - years: women ( %) and men ( %): ( %) pts were overweight, ( %) pts had bmi . ae . kg/sq.m, pts ( %) -bmi . ae . kg/sq.m. % pts had hypercholesterolemia, % -glucose intolerance, % -high arterial blood pressure. all patients were undergone by the assessment of nutrition status, biochemical researches. there was executed food allowance correction and added complex of physiotherapeutic treatment. control examination was carried out in weeks by body structure definition by bioimpedance analysis and biochemical blood tests. results: there were noted that level of cholesterol decreased from . ae . mmol/l to . ae . mmol/l (p . ), level of blood glucosefrom . ae . mmol/l to . ae . mmol/l. there was registered decreasing systolic arterial pressure of % of patients to . ae . mmhg (p . ) and diastolic at % pts -to . ae . mmhg (p . ). there were fined reduction of a fatty component on . ae . by kg, with preservation of active cellular weight - . ae . in kg (p < . ) in patients. conclusions: physical exercises, physiotherapeutic procedures jointly balanced food allowance promote more considerable decrease in weight of body and decrease in cardiovascular and metabolic risks. results: after adjustment for sociodemographic and lifestyle factors, the relative risk (rr) of pd comparing subjects with metabolic syndrome to those without it was . and the % confidence interval ( % ci) . - . . this association was especially due to high serum triglyceride levels ( ! . vs. < . mmol/l, rr . , % ci . - . ), and high plasma glucose levels ( ! . vs. < . mmol/l, rr . , % ci . - . ). the results remained after excluding the first years of the follow-up. after this exclusion and further adjustment for other components of the metabolic syndrome, the suggestive association between pd and bmi was strengthened ( ! kg/m vs. < kg/m , rr . , % ci . - . ). conclusions: high serum triglycerides and plasma glucose levels predicted low pd incidence, even after excluding the presumable preclinical disease phase. also, the suggestively increased pd risk in subjects with high bmi varied according to the follow-up time, proposing that an adequate time period should be considered to account for the preclinical disease phase in pd. pancreatic intrinsic nervous system (pins) maturation goes on postnatally and is involved in the control of pulsatility and amplitude of insulin secretion (is), both altered in obese and diabetic patients. the aim of our study was to determine the impact of obesity in infancy on pins maturation and control of is. c bl/ j mice aged weeks received a normal (nd) or a western diet (wd) for weeks. weeks old mice were used as initial controls (t ). after sacrifice, pancreases were placed in organ incubators for h. the impact of pins upon is was studied by adding to the culture the nicotinic receptors agonist dmpp in presence or absence of l-name (inhibitor of nos) or snp (no donor). insulin was assayed in culture supernatants. pins density and phenotype were determined by ihc. pins density was less in nd compared to t mice, whereas there was no difference between wd and t mice. cholinergic innervation significantly increased with age in both wd and nd mice whereas nitrergic innervation increased in nd mice and decreased in wd. pins stimulation by dmpp induced a time-dependent increase in is, significantly larger in nd compared to wd mice. is profile was identical in wd and t mice. addition of l-name inhibited dmppinduced is in nd mice while snp tended to reduce it. neither l-name nor snp altered is in wd mice. our study suggests that wd induces neuroplastic changes in the pins that could be involved in pancreatic dysfunctions observed during obesity. purpose: inflammation drives the progression from central obesity to insulin resistance, metabolic syndrome and hypertension. whether inflammation caused by allergic diseases such as allergic rhinitis can predispose to hypertension is controversial. therefore, we studied the association between hay fever and hypertension in the united states national health and nutrition examination survey (nhanes). we analyzed data on men and women in nhanes nhanes - . we included participants aged years or older who had valid data on hay fever and hypertension. results: . % of the participants had a previous diagnosis of hay fever and . % of them had hypertension. there were ethnic differences in the prevalence of previous hay fever diagnosis (p < . ) and hypertension (p < . ). overall, there was no significant association between previous hay fever diagnosis and hypertension. in women aged - , there was an association between previous hay fever diagnosis and hypertension (or = . , % ci = . - . , p = . ). this association was not diminished after adjustment for age, race and body mass index (or = . , % ci = . - . , p = . ). after further adjustment for physical activity, alcohol consumption, smoking, liver enzymes, c-reactive protein and ige level, the association remained significant (or = . , %ci = . - . , p = . ). conclusions: in this nationally representative population-based survey, previous hay fever diagnosis is not significantly associated with hypertension in adults, except for women aged - . further work is needed to confirm that this is a true association. the university of hong kong, hong kong, hong kong s.a.r. objective: beta- microglobulin (b m) is the light chain of the major histocompatibility complex class molecule. glycation of b m renders it toxic. serum b m level predicts mortality in chronic kidney disease and some malignancies such as multiple myeloma. we hypothesized that it also predicts mortality in people with diabetes. research design and methods: participants of the third national health and nutrition examination survey aged or above who had diabetes or were on medication for diabetes were included in the analysis. results: during a median follow-up of . years (range . - . years) and . person-years, ( . %) and ( . %) participants died from diabetes-related causes and all causes, respectively. tertile of b m was significantly associated with allcause (hazard ratio (hr) = . , % ci: . - . ) and diabetesrelated mortality (hr = . , % ci: . - . ). the association was independent of cardiometabolic risk factors, cancer, microalbuminuria and impaired glomerular filtration rate. conclusions: serum b m level is a novel independent predictor of diabetes and all-cause mortality in people with diabetes. an elevated level is associated with a substantially increased risk of death. metabolic syndrome (ms) refers to a constellation of factors that increase risk of cardiovascular diseases (cvd) and diabetes. insulin resistance and associated abnormalities is considered to be a link between obesity and cvd. our ongoing study investigates relationship of anthropometric, metabolic and cardiovascular parameters in young patients with incipient ms (young lean subjects with essential hypertension; ht) and obese otherwise healthy subjects (ob) in comparison to healthy lean controls (c) similar for age and sex. methods: all subjects underwent the oral glucose tolerance test. the insulin sensitivity index according matsuda (isimat) and ir homa were calculated. fasting serum concentration of total cholesterol (tchol), hdl cholesterol, triglycerides (tg), and uric acid as well as fasting and post load plasma glucose and insulin concentrations were measured. results: young lean ht patients had comparable bmi but higher body fat percentage (p = . ), higher fasting plasma insulin (p = . ), slightly higher uric acid (p = . ), and higher t-chol (p = . ) than c. despite ngt, ht patients had lower isimat (p = . ) and higher ir homa (p = . ) than controls., but these parameters were comparable to the ob group. / of young lean ht patients similarly to ob otherwise healthy subjects exhibited three and or more features of ms. conclusions: young lean patients with hypertension displayed signs of insulin resistance comparable to obese subjects and metabolic abnormalities typical for metabolic syndrome. early life style interventions might prevent theto development of complete ms in these young ht and ob subjects. increased prevalence of overweight in male patients, whereas women had increased prevalence of obesity (grade ii and iii). hypertensive diabetic subjects with other metabolic risk factors are more prone to microvascular and macrovascular complications. methods: eighty-six patients were divided into two groups. the group included subjects (mean age . ae . years) with ah and ao (mass body index (mbi) . ae . kg/m ) and the group - subjects (mean age . ae . years) without metabolic disorders. the parameters of -hour bp monitoring; microalbuminuria and mdrd; total cholesterol, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, triglyceride, diene conjugates (dc), malonic dialdehyde (md), catataze and inflammatory markershomocysteine, high-sensitivity c-reactive protein (hs-crp) and fibrinogen were estimated. results: in group there was registered increase in mean -h and daytime systolic bp, time and square indices, in night time systolic and diastolic bp variability. in renal function factors there was registered increase mdrd. in biochemical parameters there was detected increase in total cholesterol, triglyceride level, md and dc level, fibrinogen and hs-crp level; and decrease of catalase level; high density lipoprotein cholesterol compared to group . besides in group positive correlation between lipid and inflammatory markers against each other and with parameters of -h bp monitoring, microalbuminuria, mdrd and mbi was found. conclusion: we revealed relationship between blood pressure profile parameters, renal function parameters, atherogenic lipid profile parameters, inflammatory markers and mbi, that is indicative of development of cardiovascular and cardiorenal risk in patient with ah and ao. there is considerable interindividual variation in therapeutic response to metformin in women with pcos and obesity. genetic factors may play an important role in therapeutic response to metformin and tcf l gene could be one of such factors. tcf l marker is one of the strongest risk factors known for predicting increased likelihood of conversion from prediabetes to t d. tcf l belongs to a subfamily of tcf -like hmg box-containing transcription factors. tcf l is a component of the wnt-signaling pathway and determine the glucoseinduced insulin secretion and regulates the maturation of β-cells of the pancreas from pluripotent stem cells. in addition, this gene plays an important role in adipogenesis and differentiation of adipose tissue. the aim of our study was to evaluate the efficacy of using metformin in patients with pcos and obesity in relation to their rs polymorphism of the tcf l gene. patients with pcos and obesity receiving therapy with metformin were examined. comparative analysis revealed a significant increase in the frequency of genotype c/t (v = . ; p < . ; or = . ; % ci = . - . ) and t/t (v = . ; p < . ; or = . ; % ci = . - . ) in the group of patients with positive dynamics of treatment with metformin compared with the group without positive dynamics of treatment. thus, patients with pcos and obesity who possess the genotype c/t and t/t of the tcf l gene are more likely to have positive therapeutic response to metformin. objective: to investigate the relationship between resistin gene polymorphism with its circulating level, metabolic risk factor and insulin resistance in adult women. design: total healthy subjects were enrolled for the study, (age . ae . years) were with metabolic syndrome and were age matched control (age . ae . years) without metabolic syndrome. circulatory resistin, insulin, plasma glucose and lipid profiles fasting level were estimated along with insulin resistance. resistin-c g promoter region polymorphism were done by rflp method digested with bbsi restriction enzyme. results: homozygous mutant genotype (cc) (cc v/s cg + gg) (p = < . : or = . : % ci = . - . ) of the c/g resistin gene polymorphism was significantly less frequently observed in the control population. on dividing the subjects further in to two groups according to the abscence (resistin- ) and presence (resistin- ) of the mutant g allele, significantly high levels of resistin (p = . , or = . , % ci = . - . ), triglyceride (tg) (p = . ), plasma glucose (p = . ), systolic blood pressure (sbp) (p = . ), diastolic blood pressure (dbp) (p = . ), whr (p = < . ) were observed in resistin- group . conclusion: our results conclude that the c/g mutation of the resistin gene is likely to play an important role in metabolic syndrome and metabolic abnormalities. background: in both obesity and allergy, inflammation occurs. therefore, we examined the association between body mass index (bmi), a measure of general obesity, and serum ige level, a measure of allergy. excluded from this study. using the complex sampling function of spss, the unstandardized regression coefficient, b, for the relationship between bmi and the natural logarithm of ige level was calculated. results: there was a sex difference in ige level (p < . ). before adjustment, ige was associated with bmi in women (b = . , p = . ) and in the overall population (b = . , p = . ). after adjusting for race/ethnicity, age and sex except in sex-specific analysis, the association in women (b = . , p = . ) and the overall population (b = . , p = . ) remained significant. after further adjustments for physical activity, alcohol consumption and smoking, the association was still significant in women (b = . , p = . ) and the overall population (b = . , p = . ). the association was attenuated but remained significant in women (b = . , p = . ) and the overall population (b = . , p = . ) after further adjustment for levels of liver enzymes and c-reactive protein. conclusions: in this nationally representative population-based survey, ige level is associated with bmi. the attenuation in the association after controlling for liver enzymes and c-reactive protein suggests that hepatic inflammation accounts for some of the association. background: janus kinase (jak) is involved in cytokine receptormediated intracellular signal transduction. inhibition of jak protects beta-cells from cytokine toxicity and has been shown to delay the onset of diabetes in the mouse model. the influence of jak single nucleotide polymorphisms (snps) on diabetes risk or on diabetesrelated metabolic traits is unknown. methods: we therefore investigated the association of jak tagging snp rs (c>t) with metabolic phenotypes and type diabetes (t dm) in a cohort of coronary patients including non-diabetic subjects and patients with t dm, totally comprising individuals. results: among non-diabetic subjects snp rs was significantly associated with hba c (cc: . ae . , ct: . ae . , tt: . ae . %; p = . ), fasting glucose (cc: . ae . , ct: . ae . , tt: . ae . mmol/l; p = . ), and hdl-cholesterol (cc: ae , ct: ae , tt: ae mg/dl; p = . ), as well as with total cholesterol (cc: ae , ct: ae , tt: ae mg/dl; p = . ) and ldl-cholesterol (cc: ae , ct: ae , tt: ae mg/dl; p = . ). in patients with t dm, the jak variant was significantly associated with fasting glucose (cc: . ae . , ct: . ae . , tt: . ae . mmol/l; p = . ). the association between snp rs and t dm did not reach statistical significance (allelic odds ratio = . [ . - . ]; p = . ). we conclude that jak tagging snp rs is significantly associated with phenotypes conferring an increased cardiometabolic risk, at least in non-diabetic coronary patients. the association between rs and the risk of t dm warrants further investigation. l. garrido-s anchez , x. escoté , l. coín-aragü ez , j.c. fren andez-garcía , r. el bekay , j. background: munc c is associated to glucose metabolism and could play a relevant role in the insulin resistance. however, little is known on the regulation of munc c expression. we analyze munc c gene expression in human visceral (vat) and subcutaneous adipose tissue (sat) and their relationship with obesity and insulin. we evaluated subjects distributed in non-obese lean subjects, overweight subjects, obese subjects and nondiabetic morbidly obese patients ( with low insulin resistance and with high insulin resistance). results: the lean, overweight and obese persons had a greater munc c expression in adipose tissue than the morbidly obese patients (p < . ). vat and sat munc c correlated negatively with weight (p = . , p = . ) and bmi (p = . , p = . ). vat munc c correlated negatively with glucose (p = . ). sat munc c correlated negatively with insulin (p = . ) and homa-ir (p = . ), and was the main determinant of the improvement in homa-ir index at days after bariatric surgery (b = À . , p = . ). sat explants cultures show that insulin produced a significant down-regulation of munc c expression (p = . ). this decrease is also obtained when explants are incubated with a liver x receptors alpha (lxra agonist, either without (p = . ) or with insulin (p = . ). however, munc c expression is not affected when explants are incubated with insulin plus a sterol regulatory element-binding proteins- c (srebp- c) inhibitor (p = . ). conclusions: munc c gene expression in human adipose tissue is down-regulated in obesity and is inversely associated with insulin resistance. insulin may have an effect on the munc c expression, probably through lxra and srebp- c. lab., faculty of medical technology, endocrin, tripoli-university of medical sciences, biochemstry, cdc, biotechnology, research centre, tripoli, a protective factor for obesity, type- diabetes mellitus (t dm), polycystic ovary (pcos), and lacunars infarction. objectives: the objective of this study was to investigate the association between this polymorphism and t dm, gestational diabetes (gdm), and obesity. methods: genotyping was achieved by pcr-relp in individuals chosen randomly from the out patient's clinics of al-jala maternity hospital of tripoli and gharian hospital, including: t dm patients, gdm patients, obese, healthy control individuals from libyan pregnant women population (north-west region). the results revealed that this polymorphism has no association with t dm, gdm, and obesity in comparison with the control sample. conclusion: t a polymorphism of sorbs gene is not associated with the pathological conditions studied. r. parhimovich, n. konovalova, r. tishenina, n. mylov moscow regional research clinical institute named after m.f. vladimirskiy, moscow, russia area ( . ) of bmi ! . kg/m (bmi ) had significant larger areas than those of wcm ( . ). wci and bmi had good sensitivity ( . % and . %). wci and wci had good specificity ( . % and . %) and classification ( . % and . %). the proposed cutoff values were wci . further cohort study is needed to confirm these values. for national reference, we recommend measuring at umbilical due to its feasibility. servicio de endocrinologia y nutricion, hospital regional universitario carlos haya, ciberdem, servicio de cirugía, hospital regional universitario carlos haya, m alaga, spain introduction: the fndc gene encodes a membrane protein which is proteolytically cleaved, glycosylated and secreted into the blood as irisin. it has been described that causes a significant increase in total body energy expenditure, reduces body weight and improves dietinduced insulin resistance in mice. however, little is known in human. the aim of this study was to analyze the irisin levels in morbidly obese subjects undergoing bariatric surgery at baseline and months after surgery. material and methods: we measured serum irisin levels in morbidly obese subjects undergoing roux-en-y gastric bypass and in healthy controls. we have analyzed anthropometric variables and the level of insulin resistance with the homa-ir index. results: morbidly obese patients have a lower serum irisin levels that control subjects ( . ae . vs. . ae . ng/ml, p = . ). serum irisin levels were similar before and after bariatric surgery in morbidly obese subjects ( . ae . vs. . ae . ng/ml; p = . ). there were no significant differences between morbidly obese subjects according to the homa-ir levels, neither before nor after surgery. irisin levels correlated negatively before surgery with glucose (p = . ), triglycerides (p = . ), cholesterol (p = . ), homa-ir (p = . ) and waist to hip ratio (p = . ). in a multiple lineal regression model, irisin levels were associated with waist to hip ratio (p = . ) after adjusting for fasting glucose, cholesterol, triglycerides, homa-ir and age. no significant correlations were found at months after surgery. conclusions: irisin levels in decreased in morbidly obese subjects and is mainly related to waist to hip ratio. results: the level of uric acid increased with age in women and had a significant difference in women of - years (r = . , p < . ). in men, the maximal level of uric acid was in the group - years. incidence of hyperuricemia among women was %, in men - %. we determined that the highest level of triglyceride, cholesterol, systolic and diastolic pressure was among women and men with hyperuricemia. the higher level of uric acid was found in patients with maximal body mass index (bmi > ). incidence of hyperuricemia among women in the i group was . %, in ii - . %; in iii - . %, in iv - . %. conclusions: it was determined that the level of uric acid was increasing with age and the highest level of some components of metabolic syndrome (triglyceride, cholesterol, systolic and diastolic pressure) was among patients with hyperuricemia. introduction: cushing's disease (cd) is the most common reason of endogenous hypercortisolaemia. the cortisol excess leads to serious metabolic and cardiovascular complications which significantly increase the morbidity and mortality in cd. objective: to assess the prevalence of preoperative glucose homeostasis alterations in cd and their influence on the effectiveness of surgical treatment. material and methods: a prospective study that included patients ( women; six men) with cd. the prevalence of prediabetes (impaired fasting glucose, impaired glucose tolerance) and overt diabetes was assessed. the relationship was evaluated between duration of cd symptoms and the presence of glucose homeostasis alterations as well as their impact on the efficacy of surgical treatment for cd. the proportion in the study group of overt diabetes was . %, whereas the prevalence of prediabetes was . %. . % of patients were obese (bmi ! ) and additional . % were overweight (bmi ! ). there was confirmed the association between duration of cd symptoms and occurrence of diabetes (p < . ) and any type of glucose homeostasis alterations (p = . ). there was no relationship confirmed between the presence of glucose homeostasis alterations and efficacy of transsphenoidal surgery for cushing's disease. conclusion: a longer duration of cd symptoms was associated with greater risk of metabolic complications such as: prediabetes and secondary diabetes. the efficacy of surgical treatment for corticotroph adenoma does not depend directly on the presence of preoperative glucose homeostasis alterations. objective: the study objective was to identify factors associated with depressive symptoms in elderly with metabolic syndrome. material and methods: it was a case-control study to check sociodemographic and lifestyle influencing depressive symptoms in elderly patients with metabolic syndrome. the cases were attended in program family health strategy, classified as having metabolic syndrome and depressive symptoms and the control group consisted of individuals with metabolic syndrome who didn′t have depressive symptoms. it was used as a measure of association, odds ratio (or) with confidence interval of % and p-value, obtained by conditional logistic regression model. conclusions: in the population studied showed that depression was associated with individuals at higher stress levels, those who had shown the mourning, elderly older than years, those with cognitive deficits and negative perception of health. the results reinforce the need to train health professionals so that they can identify and intervene in this population, to improve the quality of life for seniors. introduction: vascular endothelial growth factor (vegf) is said to play key role in pathogenesis of diabetic nephropathy by upregulating the expression of endothelial nitric oxide synthase (enos). human vegf gene, located on chromosome and is highly polymorphic. insertion/deletion (i/d) polymorphism of the bp fragment at position of the promoter region of vegf gene has been implicated in many diseases of angiogenic origin. aim of the study: to investigate i/d polymorphism of vegf gene in patients with type diabetes mellitus and to assess their possible role in diabetic nephropathy. materials and method: fifty subjects with diabetic nephropathy, subjects with diabetes mellitus without nephropathy and normal controls were evaluated for i/d polymorphism of the bp fragment at position of the promoter region of vegf gene by polymerase chain reaction. the frequency of vegf alleles and genotype distribution were compared in diabetic subjects, diabetic nephropathy subject and control groups. results: distribution of vegf genotype was found to be significantly (p < . ) different amongst diabetic nephropathy subjects, diabetic subjects and controls by fisher's exact test and chi square test. statistically significant association (p < . ) of d allele was also found with diabetic nephropathy. conclusion: our study shows that i/d polymorphism of the bp fragment at position of the promoter region of vegf gene is associated with diabetic nephropathy. university of delhi, new delhi, india between bai, bmi and percent body fat (pbf) in an endogamous population of india. design: data was collected on adults with respect to bodyweight, height, skinfolds, hip and waist circumference, and blood pressure. pearson correlations was calculated for bai and bmi with pbf. differences in correlation for baivsbmi were examined using fisher z-tests. receiver operating characteristic (roc) analysis was used to compare the predictive validity, and to determine optimal cut-off values. ors were calculated to assess the risk of having hypertension using the proposed cut-off points. results: the correlation of pbf with bmi (men: r = . ; women: r = . ) were stronger than those with bai (men; r = . ; women: r = . ). the regression model for bai explained . % of the variance in pbf in men and . % in women whereas the corresponding regression model for bmi explained . % variance in men and . % in women. in men, the sensitivity and specificity of bai to predict hypertension was higher than wc, whr and whtr but lower than bmi. in women, the sensitivity of bai was higher than bmi and wc. in men, odds of hypertension on bai were lower than other anthropometric markers while in women, it was higher for other anthropometric markers. conclusions: bai can be used as an additional marker for screening population, however its validity needs to be demonstrated on other populations too. obesity is a multifactorial syndrome characterized by a chronic state of positive energetic balance. the experimental model of treating neonatal rats with monosodium l-glutamate (msg) was used. amino acids, which also participate in the formation of proteins, are precursors of signaling molecules as local hormones and mediators; indeed, glycine can induce catecholamine secretion of adrenal medulla. catecholamines of the adrenal medulla have an important role in the regulation of the metabolism, affecting the mobilization of fats. therefore, abnormalities in catecholamines secretion can contribute for obesity development. thus, the purpose of our work was verify if glycine administration has an inhibitory effect on hypothalamic obesity development. animals were treated with tap water added to glycine ( . g/kg). catecholamine content and secretion from adrenal medulla were measured using the trihydroxyindole fluorescence method. msg treatment induced . % enhancement of perigonadal fat pad when compared to control animals (p < . ). however, glycine treatment caused a reduction of almost % on perigonadal pad in obese group (p < . ); control-glycine group presented a decrease of . % in perigonadal fat pad related to control (p < . ). msg treatment reduced . % basal catecholamine secretion (p < . ). obese animals that received glycine presented an increase in basal catecholamine secretion ( . %, p < . ). in conclusion, we showed that glycine treatment did not inhibit obesity development, but the decrease in adiposity observed in obese and control rats treated with glycine may be consequence, at least in part, of the enhacement in basal catecholamine secretion due to stimulatory effect of the glycine. background: increased high sensitivity c-reactive protein (hscrp) and c-glutamyl transferase (ggt) have been reported to be associated with metabolic syndrome (mets) and its components. the aim of this study is to determine whether these two biomarkers independently predict new occurrences of mets in koreans. methods: on-going prospective cohort study, korea health examinee study (koex), has recruited . individuals since . among them, repeated survey was done in approximately years for individuals. only newly occurring mets cases during follow-up was included in this study. odds ratios (or) and % confidence intervals (ci) for the risk of mets were estimated using multivariate logistic regression analysis. results: three hundred seventy-six newly occurring mets cases were ascertained in the follow-up survey. two years' cumulative incidence of mets was . % and was higher among men than women ( . % vs. . %). after adjustment for potential covariates, an increased risks for newly occurring mets were observed among those with higher hscrp measured at baseline examination in men (or = . , % ci . - . ; ! . (mg/l) vs. < . (mg/l)) and in women (or = . , % ci . - . ; ! . (mg/l) vs. < . (mg/l)). also higher risk was observed in those with higher ggt in women (or = . , % ci . - . ; ! (iu/l) vs. < (iu/l)) and in men (or = . , % ci . - . ; ! (iu/l) vs. < (iu/l)). conclusions: metabolic markers such as hscrp and ggt are clearly predicted new occurrence of mets. clinical usefulness of these markers needs to be more investigated in the extended follow-up study. objective: thyroid dysfunctions are supposed to be implicated in metabolic risk. we assessed the effects of hyper-, hypo-and euthyroidism on patients′ lipid metabolism and oxidative stress from a month follow-up clinical pilot study. methods: a study cohort of probands was grouped into hyper-(n = ), hypo-(n = ) and euthyroid (n = ) patients and healthy controls (n = ). patients received their individual medication and underwent a month follow-up. routine thyroid parameters, inflammatory status, lipid metabolism and oxidative stress were analyzed in patients before and after months of medication and in healthy controls. additionally, we measured the body weight, length, waist and hip circumference, bmi as well as blood pressure (bp). results: analyses of routine thyroid parameters confirmed patient's status. anthropometric baseline characteristics were comparable between groups. bp was significantly higher in all baseline patient groups compared to controls. baseline vs. follow-up analyses revealed that euthyroid follow-ups had a significant increased bmi, waist circumference and waist-to-length ratio. further, euthyroid and hypothyroid follow-ups had a significantly lower bp. observations on lipid metabolism revealed that hypothyroid and euthyroid follow-ups showed declined hdl levels and significant higher hld-ldl ratios compared to their pre-treated state. cholesterin, ldl, tg, oxldl levels and inflammatory markers were comparable in baseline and follow-ups. concerning oxidative stress we found significantly declined asymmetric dimethylarginine (adma) levels in all three follow-up groups. results: in the elderly group without metabolic syndrome, autonomy was associated with increasing age, sedentary behavior, and depressive symptomatology. in the presence of metabolic syndrome, in addition to these factors, the lowest level of education, being insufficiently active in physical activities, and have at least one chronic disease is not transmissible, also correlated with worse autonomy. the strong association between obesity and cardiovascular disease stresses the necessity of elucidation the underlying molecular mechanisms linking these pathologies. adrenergic over-activation can promote cardiac hypertrophy and progression to heart failure. our aim was to evaluate a novel sensor for camp namely epac (exchange protein directly activated by camp) and downstream signalling pathways in the development of cardiac hypertrophy and susceptibility to ischaemia/reperfusion injury in a rat model of obesity-induced insulin resistance. methods: wistar rats on a hyperphagia-inducing diet, hid (supplementing normal rat chow with sucrose and condensed milk) for and weeks were compared to age matched controls. isolated working hearts were subjected to min global ischaemia and functional recovery was measured after min reperfusion. hearts were also freeze-clamped at different time points during ischaemia and reperfusion. epac activation was determined by rap activation kit. nfat, p mapk, erk / , pkb and creb were determined by western blotting using appropriate antibodies. results: the heart weight increased significantly after weeks on hid along with an increase in the hypertrophic marker, nuclear nfat. the weeks hid hearts recovered significantly after ischaemia compared to controls, along with a significant increase in phospho-pkb after min reperfusion, compared to week hid hearts. however, results on epac activation showed variable responses. type diabetes mellitus (t dm) and hypertension (htn), both illnesses share pathogenic mechanisms that predispose to micro/ macrovascular complications. it is well known the role of hyperglycemia and insulin resistance of diabetes in vascular endothelial dysfunction. several studies have shown the association of serum concentrations of osteocalcin (oc) in the metabolism of glucose. oc a marker of bone formation by osteoblasts and produced hormone that regulates energy metabolism, was found recently in arteries with atherosclerosis, suggesting their direct association with vascular disease. we analyzed the relationship between serum oc concentrations and cardiovascular risk factors. a cross-sectional analytical study was carried out in patients with t dm plus htn and healthy subjects (hs). oc serum levels were measured and also statistically correlated with cardiovascular risk parameters. total osteocalcin serum levels in t dm + htn subjects were significantly higher than those in hs (p < . ), whereas the uncarboxylated oc concentrations were lower in t dm + htn subjects than in hs (p < . ). body mass index, waist circumference, fat percentage, fasting plasma glucose, high-density lipoprotein cholesterol, fasting serum insulin, homeostasis model assessment-insulin resistance and high sensitivity-c reactive protein were negatively correlated with uncarboxylated osteocalcin (p < . ). in addition, carboxylated oc was also positively correlated with systolic and diastolic blood pressure (p < . ) and homeostasis model assessment-insulin resistance (p < . ). oc serum concentrations are associated with cardiovascular risk factors in patients with t dm + htn. the oc forms (uncarboxylated/carboxylated) might play different roles in cardiovascular and endocrine physiology and hence be of different value as cardiovascular risk markers. aim: to evaluate the prevalence of ms in a group of medical students from bucharest and their habits related to nutrition and physical activity. cross-sectional study: ms was defined according to international diabetes federation criteria. medical students from bucharest were included in the survey, based on their informed consent. they were examined clinically (weight, height, waist, blood pressure), provided a blood sample (glycaemia, lipids, triglycerides, cholesterol, high and low-density lipoproteins) and answered to block adult questionnaire for food and physical activity. results: students enrolled, . % females. . % of subjects were free of signs of ms, . %, . % and . % met one, two and three criteria for ms diagnosis. the highest prevalence of abnormality was found in waist (above the limit in . % cases), followed by hdl (decreased in . % cases). significant differences among genders were found in waist. food habits: boys were found to eat significantly more calories, fats, carbohydrates and proteins compared to girls. no differences for fibres, transfats, free sugar, fruits and vegetables. physical activity: boys consumed significantly more energy through physical activity, recreational activities and vigorous physical activity compared to girls. only in % of cases the energetic consume was higher than the ingestion (no difference by gender). conclusion: high prevalence of unhealthy habits related to nutrition and physical activity in a particular highly educated young group are concerning for the occurrence of ms in the future. triphala an age old commonly used powered preparation of three medicinal dried plant fruits amla (emblica officinalis), harad (terminalia bellirica) and bahera (terminalia chebula) in equal proportionsis used in indian systems of medicine. present work evaluated the anti-hyperglycemic, anti-hyperlipidemic, and antioxidant potentials of 'triphala' formulation viz., (emblica officinalis: terminalia bellirica: terminalia chebula:: : : ) in subjects with igt and tiidm. the therapeutic effect of 'triphala' administration ( gm bd) in tiidm, igt and healthy individuals was assessed by monitoring blood glucose at days intervals, hba c, lipid profile, oxidative stress markers, and liver & kidney function markers at days intervals. dna damage was assessed by comet assay, flow cytometry and hoechst nuclear stain. molecular markers were determined in the beginning and at the end of therapy. results: 'triphala' ( : : ) administration for year significantly brought down blood glucose levels with a marked improvement in lipid profile in all the groups, this was further supported by increased protein expression of ampk and adiponectin. triphala provided resistance to oxidative stress generated not only by the increasing the antioxidant enzymes activity, but also by shortening comet tail length and number of cells in g phase of cell cycle. our results indicated that diabetes is strongly associated with elevated levels of ar, tnf-a, il- and il- , but triphala down regulated the same, proving its anti-inflammatory potential. conclusion: these observations raise the prospects of using triphala formulation for treatment of diseases associated with oxidative stress and imbalanced cytokine production. introduction: glucoregulation disorders are a state of pre-diabetes increasingly diagnosed in the general population. its association with hypertension, increases the risk of cardiovascular morbimortality objective: identify the blood pressure profile in patients with disorders of carbohydrate. patients and methods: this monocentric study has permitted the prospective recruitment of patients. all had an oral glucose tolerance test (ogtt) with a mesure of plasma glucose level immediately before and h after taking g of glucose. clinical examination with taking blood pressure to two arms and a cardiovascular evaluation were performed. results: the glucoregulation disorders were concerned with patients ( %) with an average age of . years ( - years). sexratio: . . ifg was found in patients. ogtt revealed diabetes, igt. only patients with glucoregulation disorders have normal blood pressure. seventy-two patients have been followed for high blood pressure and five patients are newly diagnosed. more than a half of these hypertensive patients has an igt and a third is diabetic. in the family, the high blood pressure is reported in %, the early cardiovascular events are dominated by myocardial infarction and stroke. in high blood pressure group, patient/ is dyslipidemic and metabolic syndrom, as defined by idf , is concerned with patients/ . as for as cardiovascular events, they are reported in patients/ . (t dm) is an ongoing concern and adequate treatment remains an important issue. thiazolidinediones (tzds) are a class of drugs that initially showed great promise as unique receptor-mediated oral therapy for t dm. the tzds, rosiglitazone (rosi) and pioglitazone (pio) were widely used as hypoglycemic drugs in patients with t dm, but a host of serious side effects, primarily cardiovascular, have limited their use. aim: in the present study we have used a systems biology approach to assess specific gene expression profiles underlying the pathological processes in the heart of pre-diabetic mice treated with rosiglitazone or pioglitazone. results: our data demonstrate that both rosi and pio efficiently decreased high fat diet-induced plasma glucose and insulin levels. analysis of the heart demonstrated that rosi, but not pio, led to an increase in atherosclerotic plaque formation and an increase in heart weight to body weight ratio. a combined transcriptomics and bioinformatics approach revealed specific regulatory pathways that may explain the adverse heart effects associated with rosiglitazone but not pioglitazone treatment. conclusion: our data provide new insights into the mechanisms underlying rosiglitazone and pioglitazone action within the cardiovascular system, including drug efficacy and cardiotoxicity. a. vlassopoulos , m. lean , e. combet human nutrition, school of medicine, university of glasgow, glasgow, uk introduction: the new hba c criteria for diagnosis of pre-diabetes have been criticised for overdiagnosis, because many more people are diagnosed than with the old ogtt criteria. it is possible that some elevation of hba c is not driven by hyperglycaemia. aims: this study assesses associations of hba c, commonly assumed to relate solely to glucose concentration, with, . smoking, a major source of reactive oxygen species (ros) and . fruit & vegetables consumption associated with improved redox status. methods: one-way anova, chi-squared and multivariate linear regressions, adjusted for all known confounders were used to explore associations of hba c with self-reported smoking status and fruit & vegetables consumptions in the scottish health surveys - , among individuals without known diabetes and hba c < Á %. results: compared to non-smokers (n = ), smokers (n = ) were younger, consumed less fruit & vegetables, had lower physical activity levels, lower bmi, higher hba c and crp (p < Á ). hba c was higher in smokers (p < Á ) by two sds ( Á %), and . sds higher ( Á %) in heavy smokers (> cigarettes/day) than nonsmokers. smokers were twice as likely to have hba c in the 'prediabetic' range ( . - . %). pre-diabetes and low grade inflammation did not affect the associations. for every extra g vegetable portion consumed, hba c was . sds ( . %) lower (p = . ), but fruit consumption did not impact on hba c, within the low range of consumptions in this population. conclusion: this study adds evidence for a neglected link between oxidative stress and protein glycation, with implications for individuals exposed to ros and for epidemiological interpretation of hba c. v. aursulesei, i.c. roca, l. mihalache objective: to assess the relation between the traits of metabolic syndrome (ms) and the parameters with independent prognostic significance for cardiovascular risk. material and methods: hundred and forty-three patients were included according to the number of traits of ms ( . % arterial hypertension, . % abdominal obesity, . % low hdl-cholesterol, . % high tryglicerides, . % abnormal oral glucose tolerance). the markers of cardiovascular damage were assessed: pulse wave velocity (pwv -complior method), carotidian intima media thickness (imt), left ventricular hypertrophy (index of mass -lvmi and geometric patterns), flow mediated vasodilation (fmd), microalbuminuria (absent/present), ankle-brachial index (abi). results: in our study the cardiovascular damage is present in . %. pwv values increase with number of traits of ms (t-test) after adjusting for confounders/other cardiovascular risk factors (ancova). decreased abi is related with each of ms traits; the power of correlation depends on criteria association. pwv and abi are both related with postprandial hyperglicaemia and systolic blood pressure (p < . ), while imt is strongly related with hdlcholesterol (r = . , p = . ). lvmi and concentric hypertrophy pattern are also related with systolic blood pressure (r = . , p < . ), while eccentric pattern relates to waist circumference (r = . , p < . ). we cannot establish a relation between traits of ms and fmd or microalbuminuria. conclusions: hyperglicaemia and systolic blood pressure are best related with parameters of cardiovascular risk, but the clustering of ms components may interact to synergistically affect the extent of cardiovascular damage. pwv, abi and left ventricular hypertrophy should be systematically used for defining cardiovascular risk in ms. interleukin- (il- ) is pleiotropic cytokine with a key impact on immunoregulation and nonimmune events. sudies have investigated the role of action/lack of action of il- in the pathogeneses obesity, insulin resistance, type diabetes. aim of the study: to evaluate il- activity in hypertensive patients depend on prediabetes presence. materials and methods: hypertensive patients were examined. common clinical investigations were provided. il- plasma levels were detected using elisa. data is represented as me (q -q ). median test were used, p < . . results: prediabetes was observed in . % of hypertensive patients in % insulin resistance in hypertensive patients with prediabetes vs. % insulin resistance in hypertensive patients were detected. hypertensive patients with prediabetes ( . ( . - . ) %) characterized by significantly higher glycated haemoglobin levels as compared hypertensive patients ( . ( . - . ) %, p < . ). hypertensive patients were characterized by increased il- activity ( . ( . - . ) pg/ml). in hypertensive patients with prediabetes decrease il- activity ( . ( . - . ) pg/ml) were found. conclusion: hypertensive patients were characterized by increased il- adipose tissue is now recognized as a complex organ with a crucial role in energy metabolism and in the development of obesity and metabolic syndrome. modified response and metabolism of hormones has been observed in the visceral adiposity during obesity, specifically related to cortisone. the aim of this study was to assess the response to different concentrations of cortisone in adipocyte cell line t l . the expressions of β-hsd , enzyme responsible for the reduction of cortisone to cortisol, and aqp , involved in glycerol transport, were quantified after treating differentiated cells with cortisone at doses of , . , , and lmol/l during , , , , min, and h. total rna and cdna were obtained from the samples to develop a real time pcr using mnsod as housekeeping gene. results suggest time and dose dependent response of β-hsd and aqp ; increases in the expression were observed during the first min of treatment ( and fold, respectively), followed by expression decrease for both in a min period (p < . ). for the treatment with lmol/l cortisone, both proteins expressions showed quadratic tendencies, β-hsd tendency is described by the equation y = . + . x À . x while aqp tendency is described by y = . À . x + . x . it can be concluded that long term effects of cortisone over adipocyte metabolism may be modulated by the induction or repression of proteins like aqp and should be explored in obese individuals. objective: to present a series of cases of metabolic syndrome patients suffering sleep disorders in which the most relevant metabolic marker is serum tryglicerides levels. it has been considered that the key meatbolic alteration underlying metabolic syndrome is a resitance to insulin action. however, there could be other metabolic abnormalities that may lead to the devleopment of the clinical feautres of this diseasea. materials and methods: patients undergoing a medical check up at medica sur hospital were included. each patient was assesed in order to determine both matabolic syndrome and a current sleep disorder. anthropometric measures were taken, body rates were calculated and blood samples were taken for laboratory tests (serum glucose, tryglicerides and cholesterol levels determination). results were analysed with the spss software. results: fifteen patients meeting the world health organization metabolic syndrome were included, and who referred snoring, difficulties on getting asleep or frequent waking up while sleeping. anthropic measures, and lab results were. discussion: yet, the majority of these patients do not have serum glucose abnormalities, but mainly their weights correspond to overweight and to a phenotype of central adipose tissue distribution. the most significant metabolic alteration, in this set of patients, was hypertigliceridemia. this results suggests that there may be other metabolic pathways leading to the development of this disease. introduction: prediabetes, a condition leading to diabetes and cardiovascular diseases (cvd). in cameroon, few studies have been done about this health indicator. aims: to determine the prevalence of prediabetes and diabetes in cameroon cohort, and to compare metabolic risk factors between normoglyceamia and prediabetes individuals. patients and methods: a sample of cameroonian men and women ( - years) participated in a health survey. statistical analysis of data compared risk factors between three subgroups: normoglyceamia (ng), prediabetes (pd) and diabetes (dt). prediabetes was defined as a glyceamia of - mg/dl. metabolic syndrome (mets) was diagnosed using the national cholesterol education program (ncep) definition. results: the distribution of ng, pd and dt prevalence in the overall sample was . %, . % and . % respectively. the prevalence of mets in those with pd ( . %) was significantly higher than in those with ng ( %). many significant differences between ng and pd subjects were also noticed. conclusion: in this study, approximately % of the population who were found to be diabetic and prediabetic is at risk of cardiovascular diseases. our findings also show that prediabetes individuals are different from those with normal glycaemia in a great number of metabolic abnormalities including a higher prevalence of mets. prevention and control measures should be set urgently. research design and methods: prospective study of the thai comprehensive cirs was further evaluated by multiple logistic regressions. in determine the ability of the thai comprehensive cirs scores in predicting each outcome, the adjusted odds ratio was calculated, and backward stepwise selection was used in the statistical modeling. results: there were also prospective correlations between the baseline thai comprehensive cirs instrument and -month outcomes). total score at baseline emerged as significant predictors of -month qol (r = . - . , p < . ). every subscale of the thai comprehensive cirs was significantly related to patient satisfaction (r = . - . ), with only the neighborhood subscale as a significant predictor for adl (r = . ). the other outcomes (self management behavior, cost of care, and dbp) were not significant concurrent baseline predictors. method: we collected laboratory results of body mass index (bmi), blood pressure, fasting glucose, lipid profiles (total cholesterol, triglycerides, ldl-and hdl-cholesterol level) and visceral fat amount of cancer survivors who visited health promotion center at seoul national university hospital. an age and sex-matched control was selected randomly for each cancer survivor from visitors of this center. we compared blood pressure, fasting glucose, lipid profiles and visceral fat amount between cancer survivors and controls using multiple regression analysis after adjustment for bmi. results: one hundred fifty five cancer survivors and controls were included in statistical analyses. cancer survivors tended to have lower bmi compared to controls ( . ae . kg/m vs. . ae . kg/ m , p = . ) after adjustment for bmi, cancer survivors showed lower fasting glucose level ( . ae . mg/dl vs. . ae . mg/ dl, p = . ). however there were no significant differences of blood pressure, lipid profiles or visceral fat amount. background: both insulin deficiency and resistance are reported in patients with β-thalassemia major (btm). we assessed the ogtt and -h continuous glucose concentration by the continuous glucose monitoring system (cgms) and calculated homeostatic model assessment (homa), and quicki in adolescents with btm on regular blood transfusions and iron-chelation therapy. results: in adolescents with btm (age: . ae years), ogtt, ( %) showed impaired fasting blood (plasma) glucose concentration (bg) (> . mmol/l). two-hour after the glucose load, one of them had bg = . mmol/l (diabetic) and two had igt (bg > . and < . mmol/l). monitoring the maximum (postprandial) bg using cgms, adolescents had diabetes ( %) (bg > . mmol/l) and nine had igt ( %). homa and quicki revealed levels < . ( . ae . ) and > . ( . ae . ), respectively, ruling out significant insulin resistance in these adolescents. neither fasting serum insulin nor c-peptide concentrations were correlated with fasting bg or ferritin levels. the average and maximum blood glucose levels during cgm were significantly correlated with the fasting bg (r = . and . , respectively, with p < . ) and with the bg at -h after oral glucose intake (r = . and . respectively, with p < . ). ferritin concentrations were correlated with the fasting bg and the h blood glucose levels in the ogtt (r = . , and r = . , respectively, p < . ) as well as with the average bg recorded by cgm (r = . , p < . ). conclusion: cgm has proven to be superior to ogtt for the diagnosis of glycemic abnormalities in adolescents with btm. background: in obese children pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type diabetes (t dm). objectives: to assess oral glucose tolerance, -h continuous blood glucose concentrations (cgm) and calculate homeostatic model assessment (homa), and the quantitative insulin sensitivity check index (quicki) in children and adolescents with simple obesity (bmisds = ae . ). results: ogtt performed in obese adolescents ( . ae years) revealed three cases ( %) with ifg (> . mmol/l), four cases ( %) with igt (> . < . mmol/l), and none with diabetes. using the cgms, ift was detected in four cases, the maximum bg ( h or more after meal) was > . and < . mmol/l (igt) in nine children ( %) and > . mmol/l (diabetes) in one case ( . %). five cases had a minimum bg recorded of < . mmol/l (hypoglycemia). no glycemic abnormality was detected using hba c ( . ae . %). / patients had homa values > . and quicki values < . denoting insulin resistance. beta cell mass percent (b %) = ae . % and insulin sensitivity (is) = . ae . % denoting insulin resistance with hyperinsulinaemia and preserved beta cell mass. in obese children and adolescents; cgms is superior to ogtt and hba c in detection of the glycemic abnormalities, which appears to be secondary to insulin resistance. introduction: the aim of this study is to evaluate the effect of vitamin e supplementation on glycemic control, lipid profile, inflammation markers and malondialdehyde level of type diabetic patients. material and method: thirty type diabetic patients were participated in this randomized single blind placebo controlled clinical trial study. fasting blood glucose, serum triglyceride, total cholesterol, ldl, and hdl-cholesterol concentration, malondialdehyde (mda), hs-crp, il- , and insulin level were measured. each subject then given a breakfast that was contained g fat. subjects' post-prandial biochemical measurement was measured as well. patients' then randomly divided in two groups. treatment group received vitamin e ( iu/per day) and control group received placebo for weeks. at the end of weeks baseline procedure was repeated and fasting, and -h postprandial biochemical markers were measured. statistical analysis: data analyzed using mann-whitney u test to compare the mean differences between both groups. basic data expressed as mean ae standard deviation, fasting and postprandial biochemical parameters before and after intervention expressed as median. results: no significant differences were found in fasting and postprandial lipid profile, glucose, insulin and homa-ir after weeks of intervention between two groups. significant decreases in fasting and postprandial serum mda levels in treatment group were recorded. no significant differences were shown in fasting and postprandial inflammatory markers except fasting il- . the result of this study shows that short term supplementation of vitamin e is safe and effective in decrease oxidative stress in type diabetic patients. objective: there is evidence that patients with normal weight and central adiposity (elevated waist circumference and waist-hip index) present a higher cardiovascular and metabolic risk. it has been proven that central adiposity is a risk factor for elevated systolic and diastolic pressure amounts, low hdl cholesterol and altered glucose while fasting. materials and methods: patients treated at the integral diagnosis and treament center of medica sur hosptial were inclued. anthropometric measurments were taken and metabolic (glucose and profile of lipids with ultrasensitive reactive c protein) parameters were analyzed. results: nine hundred and forty patients were included. women with a normal body mass index but with a waist > cm, had metabolic alterations on serum lipids which have a statistical significance when compared with those women with a waist circumference lesser ran cm. an elevated waist circumference diameter, regardless of the bmi, increases the metabolic risk. the measurement of the circumference of the waist and the hip must take place by routine in any medical evaluation. aim of the study: to study the prevalence of prediabetes in elderly age group ( years and above) and to study cardiovascular risk factors in prediabetic group. methodology: study was conducted on patients of age years and above. they were screened for prediabetes as per ada guidelines . such prediabetic study group ( cases) was investigated for cardiovascular risk factors (obesity, hypertension, microalbuminuria, crp, retinopathy, dyslipidemia) along with age matched controls. standard statistical tests were applied for analyzing data. hypertension and retinopathy with the prediabetic state. risk factors are more associated with igt as compared to ifg. conclusion: prediabetes is widely prevalent in the elderly population. it has strong association with metabolic syndrome. prevalence of igt is higher as compared to ifg. similarly, cardiovascular risk factors are widely prevalent in the prediabetic population. dyslipidemia, obesity, microalbuminuria, hypertension and retinopathy share the significant association as risk factors. early identification, of prediabetic state followed by primordial and primary prevention of cardiovascular disease should be the focus of intervention. background: despite commonly using body mass index (bmi) in diagnosing obesity, the accuracy of bmi in detecting adiposity is unknown in korean. we assessed accuracy of bmi in detecting body fat percentage (bf%) defined obesity. methods: this study is a cross-sectional design of subjects (age - . years, men . %) who conducted korean national health and nutrition examination survey (knhanes iv- ) in korea from january to december . we assessed the diagnostic performance of bmi using the who reference standard for obesity of bf% ! % in men and ! % in women, which were measured by dual energy x-ray absorptiometry. we tested the correlation between bmi and bf% by sex and age groups. we defined the bmi cutoff for bf%-defined obesity using roc analysis. results: bmi-defined obesity was present in . % of men and . % of women. according to age and sex, a sensitivity and a specificity of bmi ( ! kg/m²) showed difference. the bmi cutoff value for bf %-defined obesity is . kg/m² (sensitivity %, specificity %). difference between bmi cutoff value of korean and that of american to detecting bf% is about À . kg/m². in korean, bmi showed a limited accuracy to detecting adiposity by age and sex. the difference between bmi cutoff-value of korean and that of american to detecting bf% obesity is smaller than the difference of bmi cutoff-value between the asia-pacific and who criteria. background: the healthkick intervention was developed as part of a study that aimed to address diabetes risk factors in primary schools within low-resource settings in the western cape, south africa. the intervention focused on grade - learners, their parents and the educators. aim: to ascertain the risk of developing diabetes and other noncommunicable diseases among educators. method: educators (n = ) from urban and rural schools, participated in a health check in . measurements included random blood glucose and cholesterol testing, and height, weight, waist circumference and blood pressure (bp) measurements. cut-off values for bp levels in adults years and older of the nhlbi were used for categorising hypertension. results: educators participating in this study were mainly females, with most of them ( %) falling in the age range between and years, and % being older than years. only % of educators had bps in the normal range. half of those on treatment for hypertension had levels above / mmhg, while % with bps above these levels were not on medication. about % of those who said they had diabetes (n = ) knew what treatment they were on. cholesterol levels above mmol/l were seen in %. only % said they smoked cigarettes, whereas % were previous smokers. preliminary results show that most participants had a body mass index > kg/m . conclusions: many of the educators who participated in the healthkick study are possibly at risk for developing cardiovascular and other related non-communicable diseases, such as diabetes. s.k. kota , s. ugale , n. gupta , k.d. modi endocrinology, medwin hospital, laparoscopic surgery, kirolskar hospital, hyderabad, india objective: the objective of the present study was to prospectively evaluate the results of laparoscopic ileal interposition (ii) with diverted sleeve gastrectomy (dsg) for control of type diabetes mellitus (t dm) and related metabolic abnormalities. methods: all patients underwent ii +dsg. they had t dm ! years with poor glycemic control despite adequate dosage of oral hypoglycemic agents (ohas) ae insulin. the primary outcome was remission of diabetes (hba c < . % without ohas/insulin) and secondary outcomes were reduction in antidiabetic agent requirement and components of metabolic syndrome. we report the preliminary postoperative follow-up data of . ae . months (range: - months). there were patients (m: f = : ) with mean age of . ae . (range: - years), duration of diabetes of . ae . years (range: - years), and preoperative body mass index of . ae . kg/m (range: . - . kg/m ). sixteen patients ( %) had hypertension, while dyslipidemia and microalbuminuria was present in patients ( %) each. twenty two patients ( . %) had diabetes remission. fifteen/sixteen ( %) patients had remission in hypertension. all participants had weight loss ranging between % and %. postoperatively statistically significant decline was observed in the glycemic and lipid parameters, microalbuminuria at all intervals (p < . ). patients with postoperative duration > months had better improvement in terms of reduction in glycemic, lipid parameters and microalbuminuria. three patients had vitamin b deficiency year after surgery. conclusion: ileal interposition combined with dsg addresses both foregut and hindgut theories and brings about remissions in t dm patients. background and objective: the objective of this study was to evaluate the screening potential of various anthropometric indices, namely body mass index (bmi), waist circumference (wc), waist-to-hip ratio (whr) and waist-to-height ratio (whtr) in the early detection of dysglycemia among the omani adult population. methods: our study included omani adults ( males and females) who participated in a cross-sectional, community-based study. we defined glycemic status based on american diabetes association (ada) thresholds: < . mmol/l as normal, . - . mmol/l as impaired fasting glucose (ifg) and ! . mmol/l as diabetes mellitus (dm). the cut-off values for the anthropometric indices namely, bmi, wc, whr and whtr were based on the standard definitions. the age adjusted analysis showed that out of the four anthropometric indices, among the males the whtr at the cut-point of . gave relatively higher value of odds ratio with or = . ( % ci: . , . ) and among the females whr at the cut-point of . showed maximum odds ratio with or = . ( % ci: . . . ). the areas under the roc curves, at the cut-point of ifg ! . mmol/l, was more for whtr in case of males and whr in case of females. conclusion: this study shows that out of the four anthropometric indices, there are differences in the predictive values of dysglycemia among the omani males and females. in case of males, the whtr ! . appears to be a better indicator for detecting dysglycemia whereas among the females the whr ( ! . ) is a better indicator. introduction: increased serum ferritin and iron stores are involved in the pathogenesis of insulin-resistance. polycystic ovary syndrome (pcos) is diagnosed by oligomenorrhea and hyperandrogenism. pcos and obesity were associated with elevated serum ferritin levels. the link between obesity and altered iron metabolism was proposed. object: to evaluate the association between serum ferritin levels and insulin resistance and metabolic syndrome in obese and non-obese women. methods: retrospective study. five hundred thirty-nine women, of whom had pcos and of whom did not have pcos, were included in the study. results: serum ferritin correlated with menstrual cycle length, sex hormone-binding globulin, total testosterone, androstenedione, triglyceride, and total cholesterol both in obese and non-obese women. obese women (bmi > ) with high ferritin (ferritin ! . ng/ml, n = ) levels had higher insulin resistance, impaired glucose tolerance, and liver enzymes than obese women with low ferritin levels (ferritin < . ng/ml, n = ). however, among non-obese women, insulin resistance and metabolic disturbances were not significantly different between high and low ferritin groups. women with high ferritin levels had a greater risk of pcos and hyperandrogenism than women with low ferritin levels. independent of obesity, hypertriglyceridemia was the major metabolic disturbance in women with elevated serum ferritin levels. conclusions: the pathogenesis of increased iron stores correlated with insulin resistance and metabolic syndrome among obese and nonobese premenopausal women was different. the hypertriglyceridemia in women with pcos might be associated with iron metabolism. nutrition rehabilitation, unite de dietetique, pegomas, france and yogic counseling for stress management. all subjects underwent a residential program for weeks followed by therapy at home for weeks. results were analyzed using paired 't' test. conclusion: in remote areas organization of screening on base of diabetes bus helps to detect t d and early glucose metabolism disorders in more than % of people with increased risk. findrisk scale is useful screening tool to detect these people. however, in older age groups, percentage of screen-detected t d decreases, which may indicate lower efficiency of findrisk questionnaire at age ! . background and aims: changes in the cellular oxidative status are involved in the pathogenesis of obesity-associated hepatic steatosis. the possibility of gender difference in this process was examined in an experimental model of obesity induced by a western high-fat and highcarbohydrate cafeteria diet. methods: four groups of six swiss cd mice ( day old) received either cafeteria diet (male and female) or balanced diet (male and female) for weeks. hepatic hydrogen peroxide (h o ), thiobarbituric acid reactive substances (tbars), reduced glutathione (gsh) and the activity and/or gene expression of catalase (cat), glutathione peroxidase (gpx), superoxide dismutase (sod), hypoxia inducible factor (hif- -alfa) and nuclear factor (erythroid-derived )like (nrf ) were measured. results: higher levels of tbars and mitochondrial h o were found in livers from cafeteria-fed animals of both genders, with higher levels in females. the level of gsh was lower in cafeteria-fed mice of both gender; females showed higher levels than males (cafeteria or balanced diet). cat and gpx activities were reduced in cafeteria-fed mice of both sexes; the activities in females being lower than those of males. sod activity and the gene expression of cat, gpx and sod were not significantly altered when compared by gender or dietary treatment, but the expression of hif- -alfa and nrf was increased in female cafeteria-fed mice. the female animals exhibited a higher susceptibility to cellular oxidative stress in cafeteria diet-induced obesity in comparison to males. the molecular mechanisms seem to be, in part at least, posttranscriptional. acknowledgements: capes, cnpq, fundac ßa˜o arauc aria. objectives: to investigate the relationship between body fat percentage and body mass index (bmi) among young adults aged - years. methods: young adults aged - years were recruited for study when they took health examination in september in taiwan. all subjects underwent bioelectrical impedance analysis (tanita bc- ) to estimate their body fat percentage. basic demographic data, height, and weight were collected, and bmi was calculated from height and weight. overweight and obesity were identified according to bmi. the correlation between body fat percentage and bmi was analyzed using sas software . . results: a total of male and female participants were enrolled. the mean age was . ae . years old. the mean body mass index was . ae . for men and . ae . for women. the mean body fat percentage was . ae . for men and . ae . for women. categorized by bmi, the mean body fat percentage was . ae . for men and . ae . for women in bmi < . group, . ae . for men and . ae . for women in bmi . - group, and . ae . for men and . ae . for women in bmi - group and . ae . for men and . ae . for women in bmi > group (p < . ). the prevalence of too high or obese body fat percentage among young adults aged - years in taiwan was . % in male and . % in female according to the who and nih recommendations. the cutoff values of healthy body fat percentage for young adults in chinese population ought to be modified. it is estimated that - % of women of reproductive age have polycystic ovarian syndrome (pcos). this article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with pcos. patients with pcos have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. they have an increased risk of type diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. however, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. end point studies are currently lacking and the available evidence are conflicting. this article will address the current evidence for the adverse cardiovascular risk in pcos and the other factors that may be implicated. finally the therapeutic options for treatment will be discussed. conclusion: results suggest that in the fasted condition, when fatty acids levels are elevated, the gluconeogenic flux is higher in cafeteriafed rats, a finding consistent with the higher glycogen levels. the lower production of co indicates a deviation of the citric acid cycle intermediates into the cytosol, a change which may favour the synthesis of fatty acids and triacylglycerols. these liver metabolic disturbances probably contribute to fatty liver diseases, hyperglycemia and dyslipidemia in cafeteria diet-induced obesity. certain cancers. this study aims to evaluate the association between obesity and colorectal cancer risk and also if the association varies with the blood type, age of obesity or cancer subsites. the study was carried out on hospital patients, different ages, diagnosed with colorectal cancer. we determined the blood type, cancer subsites and age of symptoms. we evaluated their family history and their lifestyle in terms of physical activity, smoking and alcohol consumption. results: out of the patients, % had the bmi ! kg/m and all of them showed abdominal obesity. the age of obesity was up to years to % of the subjects and over years for % of them. symptoms were detected over months before diagnosis for % of the individuals and between and months for % of them. in what respects the cancer subsites, % of the cases were located on the descending colon, rectum and sigma. % of the patients had a family history of different types of cancer (colorectal, pulmonary, gastric or breast neoplasia). sixty-five percent of them were smokers, % were alcohol consumers and % carry light or no physical activity. forty-nine percent were blood group a individuals. the study shows that obesity is a statistically significant risk factor for colorectal cancer and the association is stronger for the patients with a higher age of obesity, descending colon and rectum localisation of the neoplasia and blood group a individuals. technical university munich, munich, ikfe institute, mainz, germany purpose: the angiotensin ii receptor antagonist telmisartan (t) has demonstrated bifunctional effects on the hemodynamic, vascular and metabolic features of patients with metabolic syndrome (ms). accordingly, we tested the hypothesis, that antihypertensive therapy with t vs. amlodipine (a) improves diastolic myocardial function, vascular function and metabolic characteristics in ms. methods: this randomised cross-over study investigated ms patients (bmi ae kg/m ) with mild-moderate hypertension before and after months therapy with t vs. a. laboratory and ultrasound data were taken in the fasting state and h after a test meal ( g carbohydrates). cardiac function was assessed by tissue doppler as systolic (s') and diastolic myocardial velocity (e') and vascular function at the common carotid artery as elasticity modulus and pulse wave velocity. results: after months with t, fasting systolic blood pressure was reduced by ae mmhg (p < . ) and postmeal by ae mmhg (p < . ) vs. a ( ae mmhg (p < . ) fasting and insignificant ae mmhg (p < . vs. t) postmeal). with t but not with a, diastolic pressure dropped by ae (p < . ) fasting and postmeal (p < . ). with t but not a, e' increased fasting and postprandially by . ae . (p = . ) and . ae . cm/s (p = . ) and so did s' (p < . and . ), whereas vascular function improved postprandially alone (p < . and p < . ). conclusion: in ms patients, mild to moderate hypertension and without cardiac disease, monotherapy with telmisartan improved diastolic and systolic cardiac function in particular postprandially whereas amlodipine did not. introduction: the metabolic disorders at the tunisian military pilots are more and more frequent affecting more and more young subjects. the expert doctor is in front of a big problem to know the evaluation as well as the control of the evolutionary genius of these disorders to be able to minimize their complications materials and methods: it is about a retrospective study which was interested in the files of the tunisian military pilots followed regularly in the center of expertise of aeronautical medicine since . on these files, we found the various types of metabolic anomalies by referring to the age and the anthropometric characters during their appearance, as well as the evolutionary follow-up of these anomalies with or without treatment results: the metabolic disorders were found at % of the military pilots. these disorders are represented in the order by dyslipide´mies, then disorders of the hepatic metabolism, the hyper urice´mie and finally the not insulin-dependent diabetes. the therapeutic care ways begins with the hygie´no-dietary rules before the passage in the medicinal treatment. the metabolic disorders make the bed of the cardiovascular diseases; their complications particularly at the military navigators are very grave. the correction of these anomalies is imperative to avoid the vascular accidents which can be responsible for a sudden incapacity during flight. comparison to wt controls, and the epididymal fat weighs significantly less in the ko (p = . ; normalized to body weight). the irx ko mice showed increased feed and water intake relative to their body weight compared to wt littermates. moreover, qpcr and western blot analysis indicates differential expression of irx during adipogenesis in t -l cells. our data suggest that irx plays a role in the development of adipose tissue. method: forty-six obese participants (both sexes, age range from to years) group mean ae sd, . ae . years were selected for the study based on a bmi ! kg/m *. the participants were randomized as two groups. all participants were assessed for bmi and lipid profile at the beginning and end of days of the intervention. twenty six participants ( from each group) were assessed for leptin and adiponectin. the yoga group practiced yoga for min two times in a day for days. at the same time of the day the walking group practiced min of walking for two times in day. each day participants were given non calorie restricted diet regulated as kcal/day. data recorded at the beginning and at the end of the intervention were compared by repeated measures analysis of variance using spss version . , followed by post-hoc analysis. results: both groups showed a significant decrease in bmi (p < . ) and in total cholesterol (p < . ). only yoga group showed significant reduction in ldl cholesterol (p < . ) and significant increase in leptin (p < . ). the walking group alone showed a significant reduction in triglycerides (p < . ) and in adiponectin (p < . ). objective: human urotensin ii is the most potent vasoconstrictor identified to data. however, association between urotensin ii and hypertension and whether the association is independent of endothelial function has been controversial. here, we studied the association under adjustment for serum nitric oxide in a case-control study. methods: hundred and ninety-seven hypertensives and age-and sex-matched normotensive controls were studied. plasma urotensin ii, serum nitric oxide and other traditional biomarkers were examined. association between urotensin ii and hypertension was evaluated by multivariate conditional logistic regression analysis. results: hypertensives had higher levels of urotensin ii [median (interquartile rang): . ( . - . ) ng/ml vs. . ( . - . ) ng/ ml] and lower nitric oxide [ . ( . - . ) lmol/l vs. . ( . - . ) lmol/l] than normotensive controls. urotensin ii positively correlated with sbp (r = . , p < . ), dbp (r = . , p = . ) but negatively correlated with nitric oxide (r = À . , p = . ). in multivariate regression analysis, subjects in the highest th percentile of urotensin ii concentration ( ! . ng/ ml) had . times the risk of hypertension than did individuals in the lowest quartile (< . ng/ml) (p = . ). both univariate and multivariate analysis in pairs of serum nitric oxide level-matched cases and controls showed that risk of hypertension significantly and positively increased with levels of urotensin ii (all p < . ). conclusions: urotensin ii was markedly associated with hypertension and the association was independent of endothelial function. this study suggested that urotensin ii may have an etiological role in hypertension. objective: dilated cardiomyopathy (dcm) is the third most common cause of hf. the implication of transcription factors (tfs) in molecular pathways that guide heart development and cardio-specific gene expression has recently been established. however, the role of cardiac specific tfs; myocardin and tbx in the failing heart is unknown. the present study was designed with the aim to determine the expression profile and regulation of these tfs in failing hearts. methods: myocardin and tbx mrna levels were estimated by quantitative rt-pcr (qrt-pcr) in human ventricular biopsies and pbmcs of dcm patients (n = ) and controls (subjects with ventricular septal defect) (n = ). copy number variations in myocardin and tbx were determined by qrt-pcr in dcm patients (n = ) and control (n = ). myocardin and tbx promoter methylation patterns were studied in pbmcs of dcm patients (n = ) and controls (n = ) by methylation specific pcr (msp). results: myocardin and tbx mrna levels were found to be significantly six fold (p . ) and seven fold (p . ) increased in the failing human myocardium as compared to control samples respectively. promoter hypermethylation of myocardin was observed only in patients and none of controls were found to carry methylated alleles for myocardin. we did not observe any significant difference in promoter methylation status of tbx . there was no significant difference observed in the copy number of both the transcription factors; myocardin and tbx between patients and controls. conclusion: our results suggest that epigenetically regulated expression of cardiac specific tfs; myocardin and tbx may contribute to pathophysiology of dcm. introduction: mir- is among the most abundantly expressed and consistently dysregulated mirnas in heart failure and has been implicated in cardiac fibrosis. however, its role in diabetic cardiomyopathy is not known. abstracts of the th international congress on prediabetes and metabolic syndrome normalisation of the majority of indicators of lipid and carbohydrate metabolism. a.g. kistauri , g. devidze , m. jibladze , a.a. kistauri internal medicine, tbilisi state medical university, tbilisi, surgery, kutaisi ortodox christian hospital, kutaisi, georgia, lund university, lund, sweden aims: diabetic foot syndrome is a complex of purulent-necrotic and/ or ostheoarthropatic changes of the foot. in case of purulent-necrotic complications, lethality reaches - %. objectives: optimisation of infected diabetic foot treatment. methods: eight-four patients, suffering from infected diabetic foot. following was used as a material for antibioticogram: soft tissue scraping from the bottom of the injury, purulent discharge, bone biopsy. results: degree of bacterial contamination was high: between and - : anaerobic flora - . %, aerobic flora À . %. bacterial flora in purulent zone (decreased- . % to . %): staphylococcus aureus, saprophyticus, epidermidis, ps. aeruginosa, enterococcus, e. coli. the highest sensibility was shown to the following drugs (decreased- . % to . %): tienam, meronem, amoxiklav, vankomicin, cefepim, ceftriaxon, ciprofloxacin, likacin, klindamicin. less sensitivity was detected to the following drugs ( . - . %): ampicilin, doxaciclin, cefazolin, erythromycin. based on the above, the most appropriate combinations are: ftorchinolines + i-iii generation aminoglycozides (combination i) and/or iii generation cefalosporines + lincosynamides (combination ii). using the first drug combination, infection was stopped in . % and in . % of cases using the second. high amputations were performed in two cases, six more than half of foot. in cases process was stopped and amputation was avoided. conclusions: cause of tissue necrosis during neuropathic form of diabetic foot is infection, during neuroischemiccritical ischemy and infection. neuroischemic infected injury is characterised with much faster course than infected neuropathic ulcer. the most appropriate treatment combination of diabetic foot is fluorcholines + i-iii generation aminoglycozyed and iii generation cefalosporines + lincosomydes. background: continuous glucose-monitoring system (cgms) is a tool for assessment of glycemic excursions. glucose variability is a risk factor independent of glycosylated hemoglobin (hba c) for diabetic complications. aim: to evaluate the prevalence and extent of glycemic excursions & unrecognized hypoglycemia in type diabetic patients. setting and design: the study was carried out in type diabetes patients on oral agents. material and methods: patients underwent continuous glucosemonitoring by cgms for days. number and duration of glycemic excursions, unrecognized hypoglycemia, correlation coefficient (%) between cgms and self-monitoring blood glucose (smbg), mean absolute difference (%mad were analyzed. results: the mean age of patients was . ae . years. the mean hba c was . ae . %. the mean number of glycemic readings was . ae . times. the correlation coefficient was . and the mad was . ae . %, which were considerable. twenty three ( %) patients experienced hypoglycemic events. twenty seven ( %) patients had hyperglycemic events. the hypoglycemic events were found to have significant correlation with the duration of diabetes and inverse correlation with hba c, whereas age was significantly correlated with females diabetics (p < . ). conclusion: this study demonstrated that type diabetic patients have a considerable number of hypoglycemic and hyperglycemia events that may be missed by smbg. internal medicine department, zagazig university, faculty of medicine, university hospital, medical biochemistry, zagazig university, faculty of medicine, zagazig, egypt impaired fibrinolysis increase the risk of cvd in diabetics, it has been found also in igt associating metabolic syndrome but there is no data concerning fibrinolysis in subjects with normal gt that may convert to diabetes. therefore, the aim of work was to study the fibrinolytic activity, as measured by tpa activity and t-pai- antigen as markers of endothelial dysfunction in normal and igt offspring of type diabetes compared to subjects without family history of diabetes. we measured fibrinolytic activity (tpa activity and tpai- antigen) in subjects, healthy volunteers and offspring of type ( normal gt and igt), we measured fasting plasma insulin, lipid profile and insulin resistance. we found that tpa activity was significantly reduced and tpai- was significantly raised in igt group as compared to normal gt. surprisingly tpa activity was also significantly reduced and tpai- was significantly raised in normal gt. also, we found that igt increases the (tpai- antigen and decrease tpa activity in igt by . fold and . respectively than normal gt offspring. we can concluded hypofibrinolysis may aggravate insulin resistance and promote progression of atherosclerosis in those offspring in the future. this may explain the increased prevalence of cardiovascular diseases in early discovered diabetics. moreover, changes of these parameters can be used as a predictor for early detection of prediabetic state even before occurrence of glucose intolerance and the proper correction of this hypofibrinolysis may delay the development of atherosclerosis in diabetic stage. introduction: type diabetes in children is the most common juvenile endocrinopathy. decreased bone mass has been shown to be a common complication of type diabetes. the aim of our study was to evaluate the characteristics of bone mineral density (bmd) in diabetic children and their relationship with the age of diabetes, glycemic control and the biological markers of bone remodeling. with an assay of biological markers of bone turnover were performed for each child. results: sex ratio was . in the diabetic group and . in the control group. the average age of diabetics was . years and that of controls was . years. the two groups were comparable concerning the age, sex, anthropometric parameters and pubertal stage. the only difference found between the two groups concerning calcium intake that was lower in the controls. bone mineral density did not differ significantly between the two study groups. a significant difference was found comparing averages of bone markers (osteocalcin and ctx). the seniority of diabetes was correlated to the bone mineral density only in the diabetic daughter. the glycemic control represented by hba c was inversely correlated to the bone mineral density. conclusion: the prevention of bone damage in the diabetic child must go through adequate calcium intake, a proper sports activity and especially a good control of the disease. background and aims: the aim of the present study was to investigate all-cause mortality in relation to physical inactivity and diabetic status among patients surviving an acute myocardial infarction (ami). we hypothesised that physically inactive patients had a higher mortality risk compared to those who were physically active, regardless of diabetic status. methods: we enrolled n = patients with ami admitted to the coronary care unit of the central hospital in va¨stera˚s, sweden between november and may . all-cause mortality was followed-up until may . the relation between self-reported leisure time physical inactivity during the last year, diabetic status and allcause mortality was analysed univariately using kaplan-meier curves and multivariately using cox regression adjusted for the confounders bmi, prior angina pectoris, prior stroke, smoking, age, sex, education level and immigration status. p-values< . were considered statistically significant. results: a total of n = ( . %) of the ami patients had valid values for diabetics status and leisure time physical inactivity. of these, n = ( . %) died during follow-up. the mortality was significantly different (log-rank test p < . ) between physically active and inactive patients with or without known diabetes (see figure) . notably, physically inactive patients had a higher mortality regardless of diabetic status. after adjusting for confounders, the hazard rate was . (p = . ) for having diabetes and . (p < . ) for being physically inactive. conclusions: physically inactive patients had a higher mortality risk compared to those who were physically active, regardless of diabetic status. medical pharmacology, akdeniz university, antalya, turkey aims: we investigated functional effects of glp- ( - ), glp- ( - ), exendin- ( - ), exendin ( - ) and role (s) of reactive oxygen species (ros) and endothelium-derived hyperpolarizing factor (edhf) in the effects of these agents in small resistance arteries from control and diabetic rats. methods: mesenteric arterial rings were suspended in wire myograph and responses to glp- ( - ) and its analogues were recorded in the absence and presence of ros scavengers; superoxide dismutase (sod, u/ml) and catalase (cat, u/ml). role of edhf in glp- induced responses was investigated in kcl ( mmol/l)-contracted rings following incubation with no synthase inhibitor l-name ( À mol/l) and cyclooxygenase inhibitor indomethacin ( À mol/l). results: glp- ( - ) and glp- ( - ), but not exendin- ( - ) or exendin ( - ) produced concentration-dependent relaxations in mesenteric arteries from control and diabetic rats that were significantly higher in control compared to diabetic rats and in endothelium-intact compared to denuded preparations. incubation of control and diabetic rat mesenteric arteries with cat did not affect responses to glp- ( - ) and glp- ( - ) while, sod caused a significant increase in relaxant responses only in diabetic rats. glp- ( - ) and glp- ( - ) induced relaxations were significantly and similarly blunted by l-name plus indomethacin in control and diabetic rats. we provided evidence about relaxant effect of glp- ( - ) and glp- ( - ) in rat resistance arteries and about the reduced vasorelaxant effect of glp- in diabetic rats. our findings suggested that edhf played a role in glp- -induced relaxations and that increment in certain ros and/or reduction in sod function might play a role in reduced vazorelaxant responses to glp- in diabetic rats. results: significant differences for systolic blood pressure, lipids levels and kidney function between the groups are depicted in table . homa-ir was elevated in both groups, but significantly higher in the diabetic group ( . ae . vs. . ae . ; p < . ). diastolic blood pressure, crp and total cholesterol were not significantly different between the two groups. in the longitudinal group hba c levels decreased dramatically in the diabetes group ( . ae . % vs. . ae . %; p < . ), but less in the normal glucose tolerance test group ( . ae . % vs. . ae . %; p < . ). conclusion: diabetic patients with morbid obesity have a much higher cv risk profile compared with nondiabetic subjects despite presenting with the same bmi and should therefore be the preferred candidates for metabolic surgery since capacities are very limited. objective: morbid obesity (mo) has been shown to be associated with hypothyroid disorders in some patients. we therefore investigated the relationship between thyroid function parameters, bmi and insulin resistance in patients with morbid obesity before and after bariatric surgery. in patients ( . % women) with mo ( ae years; bmi . ae . kg/m ), parameters of thyroid function (tsh, ft , ft ) and homa-ir were determined before and years after bariatric surgery (weight loss À . ae . kg; p < . ). due to the lack of normal distribution, thyroid function parameters were logarithmized for statistical evaluation. results: of the patients, presented with hypothyroidism (tshrange: . - . lu/ml) before surgery, six of them with overt hypotheroidism (ft -range: . - . ng/dl). in the euthyroid patients, tsh decreased from . ae . to . ae . lu/ml (logtsh . ae . vs. . ae . ; p < . ). in the hypothyroid patients, tsh declined from . ae . to . ae . liu/ml (logtsh . ae . vs. . ae . ; p < . ). in the latter, the decline in tsh was more pronounced than in euthyroid patients (p < . ). concordantly, ft concentrations increased by . % (p = . ) and by . % (p < . ) in euthyroid and hypothyroid patients. homa-ir declined from . ae . to . ae . (p < . ) in euthyroid patients and from . ae . to . ae . in hypothyroid patients (p < . ), but did not correlate with the decline in tsh. the improvement of thyroid function after bariatric surgery is not associated with the reduction in insulin resistance. therefore the improvement of thyroid function could independently contribute to the positive long-term effects of this intervention. introduction: some years ago chronic diseases were considered to be a problem of the rich and elderly population. today we know that within high-income countries, poor as well as young and middle-aged people are affected by chronic conditions. for chronic disease, there are a small number of risk factors common to many diseases. the major biological risk factors identified in the world health report are: overweight and obesity, raised blood pressure, raised blood glucose and abnormal blood lipids and its subset raised total cholesterol. objective: was to carry out an epidemiological survey on prevalence of raised fasting blood glucose in kosova. material and methods: according to the who steps methodology the fasting blood glucose in blood sample from finger was measure with accutrend plus on sample of randomly selected participants aged - years. results: according who criteria raised fasting blood glucose is if capillary glucose is more than . mmol/l or more than mg/dl. in kosova, females are in higher risk for diabetes than males (females . % vs. males . %), total . %. prevalence of raised fasting glucose was increased with age. at the age - year the prevalence of raised fasting blood glucose was . %, at age - year . %, at age group - year %, at age group - year was . % and at the age group - year was . %. conclusion: effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequel. objectives: hypertension and hyperglycemia are features of the metabolic syndrome and diabetes. methylglyoxal (mg), a reactive glucose metabolite, is elevated in diabetic patients. we investigated whether mg induces hypertension and its molecular mechanisms. methods: male week old sprague-dawley rats were treated with mg ( mg/day by continuous infusion with a minipump) for weeks. aortic rings were used for vascular contractility, and other tissues alongwith cultured vascular smooth muscle cells (vsmcs) for molecular studies. hplc, western blotting and q-pcr were used to measure mg, proteins and mrna, respectively. sirna for angiotensinogen and the receptor for advanced glycation endproducts (rage) were used to study mechanisms. results: mg treated rats developed a significant increase in blood pressure, plasma aldosterone, renin, angiotensin (includes precursor and products), norepinephrine, epinephrine and dopamine levels. the aorta showed increased contractility to the a agonist phenylephrine. mg level and protein and mrna for angiotensin, at receptor, a d receptor and renin were significantly increased in the aorta and/or kidney of mg treated rats. treatment of cultured vsmcs with mg or high glucose ( mmol/l) significantly increased cellular mg, and protein and mrna for nf-jb, angiotensin, at and a d receptors, which were prevented by inhibition of nf-jb. silencing of mrna for rage prevented the increase in nf-kb induced by mg. silencing of mrna for angiotensinogen prevented the increase in protein for nf-jb, angiotensin, at and a d receptors. conclusions: mg activates nf-jb through rage and thereby increases activity of the renin angiotensin aldosterone system to cause increased vascular contractility and hypertension. background: guidelines state obesity as an indication for diabetes screening. abdominal obesity is valuable to manifest metabolic risk as much as and may be even more than body mass index (bmi). in this study the answer to "which is a better indicator for diabetes screening; bmi or waist circumference?" has been questioned. method: three hundred people attended to the invitation of diabetes screening in istanbul medeniyet university goztepe research and training hospital outpatient clinics. their demographic characteristics, bmi, waist circumference, fasting blood glucose (fbg), diabetes history and if diagnosed drug regimen were recorded. results: a total of individuals ( women, men) were enrolled. one hundred forty three of ( %) individuals had a bmi ! . among those people ( %) had fbg ! and < mg/dl and (% ) had fbg ! mg/dl (table ) . abdominal obesity was observed in individuals ( women, men). thirty % had known diabetes mellitus (dm). among patients with abdominal obesity and without dm diagnosis, % had dysglycemia (table ) . among obese individuals, % had a history of dm. dysglycemia rate among obese persons without a history of dm, was % (table ) conclusion: abdominal obesity is a strong predictor of diabetes as obesity and its presence should be considered as an indication for screening diabetes. internal medicine and cardiology, expertise centre of aviation medicine of tunis, mhiri, tunisia type diabetes is a rare disease compatible with aviation activity with restrictions and constraints of regular medical checks. this retrospective study was interested in drivers with type diabetes cemeda monitored since until . the aim of this work is to investigate the incidence of diabetes in the tunisian population of seafarers and show the difficulties of management of diabetic driver. sailors have diabetes type (or # %) and three student pilots (two civilians and military) had type diabetes resulting inability final flight. average blood glucose of diabetic patients was . g/l with a range of . and . g/l; glycosylated hemoglobin a c is an average of . % [range: . - . %]. the average age of diabetes is years and mean bmi of kg/m². a mild to moderate hypertension was found in % of diabetics; dyslipidemia was found in two-thirds of diabetics. the treatment of diabetic subjects: rules dietary guidelines were prescribed in only about % of cases. moreover, these measures were associated with treatment with oral antidiabetic (biguanide alone in % of cases; biguanide + pioglitazone in % of cases associated biguanide a sulphonylurea in approximately % of cases. conclusion: : the prevalence of niddm is significantly lower among sailors in the general population. the balance diabetic seafarers is the only guarantor of declining maturity of micro and macrovascular disease and strengthen the doctor′s attitude towards pn medical ethics and flight safety. methods: is a retrospective cohort study that included patients who attended a preventive evaluation unit between and , with at least three visits in that period. results: a total of patients were included, of whom ( %) had nafld at their first visit. the basal variables were similar between groups, with male predominance in the nafld group. high blood pressure and dyslipidemia predominate in the nafld group until visits and respectively. the other cardiovascular risk factors were similar until visit . the study showed a tendency to present high blood pressure, dyslipidemia and gallstones in the nafld group in a shorter period of time than the control group. levels of aspartate aminotransferase raised in a period of . vs. . years in the control group (p = . ). the study was not able to demonstrate a clear difference in the presentation of cardiovascular risk factors and liver function tests in patients with nafld and although there was a higher presentation of gallstones, it requires a larger sample and a longer follow up period to have significant results. objective: to determine the relationship between metabolic syndrome (ms) and exaggerated blood pressure response to exercise (ebp) in adolescents. methods: this cross sectional study was conducted in adolescents ( males, females), randomly selected of high schools, in maracaibo, venezuela. they underwent an exercise treadmill testing. the ms was defined according to the definition of the national cholesterol education program, adult treatment panel iii modified for adolescents. the bp was measured at rest and during the treadmill test (bruce protocol), and it was registered the systolic bp (sbp) in maximal exercise to define adolescents with ebp ( ! mmhg). statistical analysis: chi square test was used to establish associations between ms and ebp. results: the ms prevalence was . % (n = ) in all subjects, . % (n = ) in males and . % (n = ) in females (p: . ). the sbp in maximal exercise values were: . ae in adolescents with ms and . ae in adolescents without ms (p: . ). the prevalence of the ebp was . % (n = ) in all, . % (n = ) and % (n = ) in subjects with ms and without ms, respectively (p: . ). the ms is closely linked to the sbp response to exercise in adolescents. those adolescents with ms are more likely to have exaggerated sbp during exercise, indicating an important information about their cardiovascular risk. background: metabolic syndrome (mets) is a cluster of risk factors that carries a great risk for atherothrombotic events leading to significant morbidity and mortality. few studies evaluated the association between mets and acute stroke. the aim of this work was to study the prevalence of mets and its effect on icu mortality in acute non embolic ischemic stroke patients. patients and methods: we studied patients presented with acute ischemic stroke diagnosed by ct brain in the medical icu, zagazig university hospital for the presence of mets and its relation to age and sex as well as the number of components of mets. we studied also the relative risk of mets with its different components as well as age, sex, glasgow coma scale (gcs) and apache ii score on the mortality in those patients. results: mets was found in . % of patients. it was more prevalent in males ( . %). this prevalence increase progressively in males aged - years then decrease progressively while in females, prevalence increase progressively with age. . % of patients have three components of mets compared to . % with more than three components. the relative risk of mortality was found to be increased with increasing age, male gender, obesity, hyperglycemia, low hdl-c, increased serum triglycerides, lower gcs, increased map, mets per se and higher apache ii score. mets and apache ii score were good predictors of mortality. contrary to the usual approach, we could leave the future open to a bi-therapy associating glp- mimetics and dpp- inhibitors (before the supplementation in metformin and sulfamids or glitazones). case report: diabetes type in balance for years after being treated first with metformin only then added glitazone, to end by glp- mimetics at maximum doses and metformin but still not under control. it was decided to associate glp- mimetics and dpp inhibitor, ending up to a glycemia and insulin . and hba c: . . after stopping the treatment for days we observe: fast glucose , postprandial (on a diabetic diet), relative hypoglycemia generating a multi metabolic syndrome spiral. the increase of the fast glucose being explainable by the non-control of the glucagon produced during the night. pattern proposed: glucagon would not work on demand but time continuously. it has to be inhibited thanks to the glp as soon as the glycemia increases and this would be irrespective of food intake. therefore, there is no reason to use the dpp inhibitors only in case of resistance to endogen glp and let the glp -mimetics being destroyed by the dpp . this would lead to a therapeutic failure or usage of very high doses. we could treat upstream the sequence of energetic metabolism. first of all: glp -mimetics or dpp inhibitors. secondly: glp -mimetics and dpp inhibitors. those steps could be part of tomorrow′s decisional algorithm of type diabetes. abstracts of the th international congress on prediabetes and metabolic syndrome aim: to evaluate the prevalence tipe diabetes mellitus (dm ) and ischemic heart disease (ihd), and diabetogenic/atherogenic factors in patients with newly diagnosed long-term gout material: seventy males - -years (mean ) with untreated tophaceous primary gout - years (mean- ) duration (without renal insufficiency) were studied. uric acid level was fasting serum glucose, insulin (control- - , mean pmol/l), total and hdl cholesterol, triglyceride, bp and ecg monitoring mmol/l, insulin and pmol/l. one more patient, years, with ihd and triglyceride . , cholesterol . mmol/l, insulin pmol/l levels. thus, diabetes was in one and ihd in three patients two patients ( - years) with and years of gout and hyperinsulinemia thus, long-term gout (hyperuricemia) even with concomitant high bmi, insulin, cholesterol and triglyceride levels is not an evident risk factor for diabetes and ihd development. probably, antioxidative effects of uric acid play a role montes claros, brazil background: the leptin receptor is an important regulator of leptin activity and a potential mechanism for the obesity. the polymorphism leprgln arg could be associated with high body fat percentage (bf%) and body mass index (bmi) objective: to investigate the association leprgln arg with obesity indexes we obtained oral swab and anthropometric measures including waist circumference (wc), bmi and bf% for subjects aged ! years. the genotypes were determined by pcr-rflp method. the statistic analyze were carriedout in stata software. results: there were no differences of age average between sex (female . ae . ; male . ae . ). the prevalence of the overweight (bmi > kg/m ) was . %( ), normal, . % ( ) and obesity (bmi > kg/m ) . % ( ). the prevalence of high wc (> cm for women or > cm for men) was . % ( ) and . % ( ) in women and men, respectively (p = . ) and of the high bf% (> % for women and > % for men) was adiposity was not associated with genotypes. the frequencies of overweight were . %, . % and . % and of the obesity were . %, . % and . % in the genotypes aa, ag and gg, respectively. there was not also association for high wc conclusions: these findings suggest that the leprgln arg is not associated with high bf%, bmi or wc in this population hydrogen breath test (bth ), based on lack of source for hydrogen gas in humans other than bacterial metabolism of carbohydrates, is use to detect carbohydrates malabsorption aims: to evaluate the utility of bth in detect carbohydrates malabsorption in overweight-obese subjects. patients and methods: hundred and six consecutive subjects ( overweight, obese; males/ females leptin injection did not suppress ei. importantly, ts treatment reinstalled leptin sensitivity as seeing a significant decrease in ei for h (À %, p = . ) and increase of pstat level (À %, p < . ) in the hypothalamus after i acknowledgements: this work was supported by a grant of the romanian national authority for scientific research, cncs-uefiscdi, project number pn-ii-id-pce- - - ". dr. lixandru, was supported by the postdoctoral program posdru/ / . /s/ , from european social fund. this cluster-randomized controlled trial study aimed to assess the effectiveness of the interactive multi-modality technology (imm) as an intervention to increase self-management among type diabetic patients in a -month period. the imm intervention contained email, short message system (sms), and website with four main functions (i.e., selfregulation, self-monitoring and assessment, social support, and reminder system -linked to email and sms). in this trial, four public offices in bangkok metropolis were recruited and randomly assigned into either the intervention or the control group. one hundred and twenty four thai patients who had met inclusion criteria (hemoglobin a c or a c > . %, no serious illness, and internet and mobile phone accessibility) were subsequently assigned to the intervention (n = ) and the control (n = ) group. patients in the intervention group received the imm intervention. those in the control group received selfmanagement knowledge via email only. outcome measures, a c and behavioral questionnaires (diabetes quality of life, self-efficacy, and division of endocrinology and metabolism, national institute of nutrition, secundrabad, india introduction: we showed earlier that increased visceral adiposity in the offspring of magnesium deficient rats was associated with altered gene expression and increased stress.aim: to assess whether maternal magnesium deficiency modulates the gene expression of adipogenesis and insulin sensitivity in utero due to increased stress.methodology: female weanling wnin rats received for weeks, an ain g diet (control: mgc) or the same with % restriction of magnesium (mgr) and mated with control males. half the pregnant mgr dams were rehabilitated from conception (mgrc) while others continued on magnesium restriction. total rna was isolated from the mgc, mgr and mgrc embryos collected on day of gestation and expression of βhsd , pparc and adiponectin was quantified by real time pcr. body composition was determined in month old offspring by total body electrical conductivity (tobec).results: plasma magnesium levels in mgc and mgr dams before pregnancy; and month old mgc, mgr and mgrc offspring were on expected lines. mgr embryos had significantly higher expression of pparc and βhsd than mgc, whereas adiponectin expression was lower. on the other hand in mgrc th day embryos βhsd and pparc expression was restored to mgc, adiponectin expression introduction: khaya senegalensis is presently used for the treatment of diabetes in some west african countries.objectives: this study was conducted to investigate the anti-diabetic effects of the plant using in vitro and in vivo models.results: ethanolic extract of the root sample of the plant was subjected to solvent solvent fractionation which yielded a butanol fraction that possessed significantly higher (p < . ) anti-oxidative activity as well as a-glucosidase and a-amylase inhibitory activities than other (aqueous, ethyl acetate and dichloromethane) fractions. enzyme kinetic studies indicated that the butanol fraction is a non-competitive inhibitor for a-glucosidase with an inhibition binding constant (ki) of . lg/ml and a competitive inhibitor of a-amylase with a ki of . lg/ml. subsequently, the butanol fraction was subjected to in vivo studies in a type diabetes model of rats. after weeks of intervention, the fraction, at mg/kg bw, was found to improve the feed and fluid intake, body weight gain, blood glucose, glucose tolerance ability, serum insulin concentration and β cell function of diabetic animals. phytochemical analysis of the fraction through repeated column chromatography led to the isolation of bicyclo [ . . ] hexane- , , -triol. the structure of the compound was established through detailed spectroscopic methods including h nmr, c nmr and d nmr (cosy, hsqc and hmbc) experiments.conclusion: data from the study suggests that the butanol fraction of k. senegalensis contains bioactive agents that could be exploited in the management of type diabetes. objective: to determine the progression rate to impaired fasting glucose (ifg), impaired glucose tolerance (igt), and diabetes (dm ) in normal glucose tolerant (ngt) people during years follow up study using who and new criteria of ifg (ifg , -fasting glucose . - . mmol/l).research design and methods: this is an year prospective study in a randomly selected urban population aged ! years living in krakow, poland. persons had ngt. based on who criteria, ( . % of invited, men and women, aged mean . sd = . ) attended the follow-up assessment.. subjects underwent a physical and biochemical examination and questionnaire examination.results: the prevalence of dm , ifg and igt according to who criteria in examined population with baseline ngt was . %, . % and . % respectively. the prevalence of ifg , using new criteria, was . %, lowering cutoff point for ifg caused . % increase in the prevalence of ifg.among people with diagnosed diabetes % had newly diagnosed diabetes during the control study. the prevalence of dm and igt/ ifg was increasing with increasing age and bmi categories (p < . ). the lowest obesity prevalence both baseline and after follow up was found in those who remained ngt.conclusion: in the baseline ngt population high follow-up progression rate to impaired glucose metabolism was found. the implementation of new ifg diagnostic criteria increased the prevalence of ifg by . %. according to our results prevention of diabetes initiatives should focus on normal body weight preservation. results: sbp was found to be elevated in . % subjects whereas dbp was elevated among . % subjects. out of all the subjects, . % were overweight and . % obese. obese subjects were found to be more hypertensive than non-obese subjects (r = . ). sbp had strong correlation with age (r = . ), bmi (r = . ), whr (r = . ), fbs (r = . ), chol (r = . ) and ldl (r = . ) whereas dbp was found to be strongly correlated with same parameters and triglycerides (r = . ) also. no significant correlation was found with hba c levels and hdl-cholesterol. conclusion: hypertension was found to be more prevalent in males as compared to females in this diabetic population. there was an background: the medicine faculty, chiang mai university provided health screening to detect health problem and risk group for high school students who past entrance examination in this academic year . there is no official cutoff value of waist circumference (wc) measured at superior iliac crest level (wci) for overweight and obesity in thai young adolescence. we aimed to determine correlation between wci and to those measured at midpoint between lower costal margin and superior iliac crest (wcm) and to define appropriated wci and body mass index (bmi) cutoff levels for admission students in northern thailand.methods: the admission students had weight (kg), height (cm), wc, and blood pressure measurements.results: there were admission students. . % of them were female. the correlation between wci and wcm was . . for receiver operating characteristics analysis of having high bp (systolic ! mmhg or diastolic ! mmhg.) using wcm of cm in male and cm in female as standard (wcm ), area under curve ( . ) of wci of cm in male and cm in female (wci ) andabstracts of the th international congress on prediabetes and metabolic syndrome all patients were asked to follow a dietary plan for weeks before bth , day before the test, subjects were instructed to take a low fibre diet. bth was carried out both after overnight fasting (t ) and during oral glucose tolerance test (ogtt). hydrogen gas is detected in exhalate, cut-off value was settled at ppm.results: at t bth was positive in % of overweight and % of obese subjects.particularly, bth was positive in % of subjects with ms and in % of those without ms.during ogtt, % of bth results, negative at t , became positive.conclusions: obese subjects with ms had an bth altered value at t suggesting a intestinal dysbiosis.on the basis of our preliminary data, bth at t can be helpful to diagnose gastrointestinal disorders driving the idea of intestinal dysbiosis as a possible cause in pathogenesis of obesity, thus a probiotic supplementation is to be considered as baseline therapy in overweight-obesity. department of clinical physiology and pathology of locomotor apparatus, institute of gerontology ams ukraine, kyiv, ukraine aim of research: to determine uric acid level in blood serum and incidents of hyperuricemia among women and men of different age and their relation with some components of metabolic syndrome.object of research: age of examined patients was from to years old: women (n = ) and men (n = ). they were divided in following groups: i group (bmi = . - . ), ii -(bmi = . - . ), iii -(bmi = . - . ), iv -(bmi > ). average age of examined patients was . ae . years.methods: uric acid level in blood plasma was determined by uricaseperoxidase method. aim: we studied the prevalence and prognostic impact of the metabolic syndrome (ms) in acute myocardial infarction (ami) patients (pts) with normal (ngt) or abnormal glucose tolerance (agt).material and methods: a total of consecutive nondiabetic ami pts performed an oral glucose tolerance test at hospital discharge being categorized using idf/nhlbi/aha ms criteria into four groups (gr): gr. i -ngt no ms (n = ), gr. ii -ngt with ms (n = ), gr. iii -agt no ms (n = ), gr. iv -agt with ms (n = ). clinical characteristics and cv events during . years follow-up were studied.results: ms was diagnosed in % pts, with a higher prevalence in agt vs. ngt subjects (p < . ). ngtms and agtms subjects were more likely to be older (p < . ), women (p < . ), hypertensive (p < . ), have stroke history (p < . ) and hypertriglyceridemia (p < . ) compared to pts without ms. in hospital heart failure rates were higher in gr. ii, iv vs. gr. i, iii (p < . ). agtms subjects showed more often atrial fibrillation and a lower lvef% compared to ngtms (p < . ). cv events incidence during follow-up was similar among groups excepting significantly higher mortality in pts with ms, especially in agtms subjects (rr = . ( % ci . - . ) for ngtms; rr = . ( % ci . - . ) for agtms).conclusions: ms was present in % of nondiabetic ami patients and was associated with high long-term mortality; its incidence and the risk of death increased in the presence of agt. methods: a cross-sectional study was realized in government workers during his medical review, from april to september . the screening included height, weight, waist circumference, blood pressure measurements, plus a blood draw sample to determine glucose, triglycerides, and total cholesterol. body mass index (bmi) was used to diagnose overweight and obesity according to cut-offs proposed by the world health organization ( ). the mets was defined according with aha/nhlbi criteria ( ) . waist circumference (wc) and waist-to-height ratio (whr) were used as fat distribution indexes. all statistical analyses were performed using the spss v .results: in total, workers aged - years, of both sexes ( % males and % females), were included. the overall prevalence of mets was extremely high with % ( % in male, and % in female). abdominal obesity was present in . %, high triglycerides in . %, high-density lipoprotein cholesterol levels in . %, fasting hyperglycemia in . %, and hypertension in . % of the sample. % of the overweight or obese were diagnosed with metabolic syndrome. the prevalence of overweight and obese was extremely high too, according with gender: % in male, and % in female. mets was associated with cigarette smoking, absence of physical activity, a higher bmi and a greater proportion of obesity. the mets prevalence in this sector of mexican government workers is a very serious health problem. it is urgent to develop innovative programs that improve health situation. our rehabilitation department targets obesity and take care of patients a year, either in a outpatient (op, day hospital) or in patient (ip) programme.we focus on therapeutic education, and our approach is medical, nutritional, physical, psychological and social.the aim of our study is to compare the efficiency of the day hospital vs. in patient in the rehabilitation of obesity.two samples of patients who exited our unit months ago were compared.investigated criteria were: loss of weight during the programme, way of life after the programme (physical activities, diet), medical and psychological follow up.the results showed: . a weight loss between the patient admission and the trial date of . kg for in patients vs. . kg for day hospital patients. . the diet prescription is followed by . % of ip patients and by . % of op patients. . the prescription of physical activity was followed by % of ip patients and . % of op patients. . a psychological follow up is done by % of ip patients and % of op patients.the efficiency of the therapeutical education programme is proven in either ip or op patients.the day hospital allows a smooth return to normal life after a nutrition inpatient rehabilitation. research design and methods: a total of asymptomatic t dm subjects ( men and women; mean age: . ae . years) were enrolled. clinical and laboratory parameters, including hba c, glycoalbumin, lipid profile were evaluated and cardiovascular magnetic resonance (cmr) was performed. abnormal findings of cmr were defined as any one of the followings: . silent myocardial infarction. . inducible ischemia. . suspected cad.within days after taking cmr, invasive coronary angiography (ica) was performed in selective patients.results: among patients, a total of patients (silent myocardial infarction (n = ), inducible ischemia (n = ), suspected cad (n = )) had at least one abnormal finding on cmr and ica was recommended. finally, patients underwent ica, and subjects had significant cad (a total of coronary territories assess) overall, in asymptomatic t dm patients, the positive predictive value (ppv) of sp-cmr, cmr-a, c-cmr are %. however, the ppv of each mri to detect signinficant stenosis are %, % and %, respectively. in asymptomatic t dm patients, stress perfusion cmr showed higher ppv than cmr-a. introduction: observational data suggests that low -hyroxyvitamin d is associated with metabolic syndrome in diabetic and non diabetic patients. we examined the difference between components of metabolic syndrome before and after treatment with calcitriol in type diabetic patients with vitamin d deficiency.method and material: a total type diabetic patients were selected. patients had vitamin d deficiency that underwent calcitriol treatment with . lg per day for weeks. in all cases, clinical parameters including weight, systolic and diastolic blood pressure and laboratory parameters including levels of fasting blood glucose, insulin, lipid profile, calcium, phosphorous, hba c and insulin resistance were measured, before and after the treatment period. the two sets of results were then compared with one another.results: following treatment with calcitriol hba c, total cholesterol, ldl, hdl and diastolic blood pressure decreased significantly. (p = . , . , . , . and . respectively). but the changes in other parameters were not significant. subjects and methods: the five components of mets following the criteria of the international diabetes federation (idf) were measured in men (mean age . ae year) and women (mean age . ae . year) participating in the pep family heart study. we determined percentage body fat using skinfold thickness. we defined high %bf > % for females and > % for males and elevated bmi as ! kg/m². spss version was used for the statistical analyses; multiple linear regression models were used. two-tailed p < . was considered significant.results: mean values of wc, blood pressure (bp), fasting plasma glucose (fpg), triglycerides (tg), hdl-cholesterol and bmi were significantly higher in men than in women who had higher %bf ( % vs. %). using multiple linear regression models, we found significant associations with wc, %bf and bmi. bmi had the strongest associations with tg (beta . ; ci % . - . ), hdl-c (À . ; À . to À . ), sbp ( . objective: patients with esrd have an increased risk for cardiovascular morbidity and mortality. metabolic syndrome (metsy) has been implicated in the progression of cardiovascular disease (cvd). this cross sectional study investigated the prevalence of metsy in maintenance hemodialysis (hd) patients using a joint definition for metsy.patients and methods: subjects had to meet at least three of the following five criteria for metsy: elevated waist circumference, elevated triglyceride levels, low hdl cholesterol, elevated blood pressure and elevated fasting serum glucose. demographics, medical history, anthropometric and laboratory data were collected from the medical records. serum chemistries were obtained mid-week and waist circumference was measured twice after a hd session and the mean value was calculated. the study cohort consisted of % male patients with the mean age of . ae . years. hypertension was the leading cause of esrd ( %) followed by diabetic nephropathy ( %). metsy was identified in % of the cohort, with %, % and % having , and risk factors, respectively. the prevalence of metsy was highest amongst patients on hd for > years ( %). for those patients on hd < months, - months and > to < years, metsy was identified in %, % and %, respectively. metabolic syndrome was not associated with gender and age.conclusion: metsy is highly prevalent in hemodialysis patients, which suggests an additional risk for cvd. early screening for metsy may have protective role on cvd morbidity and mortality. department of family medicine, kangwon national university hospital, chuncheon, republic of korea introduction: it was reported decreased relative muscle mass was related with insulin resistance and prediabetes in us. the aim of this study is to investigate the association of relative muscle mass with cardiovascular disease risk factor using the nationally representative sample of korean adults.methods: this is a cross-sectional study using the data of the subjects who participated in the korean national health and nutrition examination survey (knhanes) in - . multiple linear regression analysis for survey design was used to explore the association between relative muscle mass and the factors of metabolic syndrome and homa-ir with adjustment for confounding factors.we also conducted multiple logistic regression analysis for survey design to investigate the relationship of relative muscle mass with metabolic syndrome.results: in comparison with subjects in the first quintile of relative muscle mass, the odds ratio ( % confidence interval) for metabolic syndrome for subjects in the fifth quintile was . ( . , . ) in the age < group and . ( . , . ) in the age ! group respectively after adjusting for confounding variables. relative muscle mass was inversely associated with sbp, dbp, serum tgs, fbs and homa-ir in both age < and age ! group, showing significant liner trend.conclusions: decreased relative muscle mass was inversely associated with the prevalence of metabolic syndrome, and the factors of metabolic syndrome except hdl-c. the causal relationship is not exactly known and would be elucidated through further longitudinal study. endocrinology, moscow regional research clinical institute, moscow, russia background: there has been growth in registered prevalence of type diabetes (t d) in russia. real prevalence of t d is much more higher. new approaches for early detection of glucose metabolism disorders are important.aim: assess effectiveness of new approach to screening of glucose metabolism disorders based on using diabetes bus in remote areas of moscow county. objective: to study the frequency of metabolic syndrome according to the atpiii criteria among elderly people attending the family practice clinic at the jordan university hospital, and to investigate the pattern of antihypertensive medications used for patients with metabolic syndrome.design: a total of elderly people ( males and females) aged years or more attending family practice clinic at jordan university hospital.materials and methods: elderly patients included were studied regarding the frequency of metabolic syndrome and its individual components according to the atpiii criteria. antihypertensive medications used by elderly patients with metabolic syndrome were also investigated.results: the frequency of metabolic syndrome was found to be . %. hypertension was the most frequent risk factor among all patients including males and females ( % in the whole sample, . % in males and . % in females). all risk factors except hypertension were significantly more frequent among patient with metabolic syndrome compared to those with no metabolic syndrome. the most commonly used antihypertensive medications were the angiotensin converting enzyme inhibitors ( . %), followed by beta blockers ( . %), calcium channel blockers ( %), and finally angiotensin receptor blockers and thiazide diuretics (both . %).conclusion: the frequency of metabolic syndrome was relatively high, which highlights the need to take some action to combat the syndrome. hypertension in particular showed the highest frequency among all risk factors. optimum control of hypertension by following the guidelines is essential in this context to better achieve control without adversely affecting the metabolic syndrome out come. introduction: metabolic syndrome is associated with a significantly increased risk of morbidity and mortality.objective: to assess incidence of the metabolic syndrome in patients of the team in the family medicine centre in kalesija through the medical audit.patients and methods: we have analyzed the medical records of all the patients with team with years of age and over ( records).we have used the international diabetes federation and the american heart association (aha) criteria for the definition of metabolic syndrome diagnosis. the analysis is done separately by sex, age and body mass index (bmi). the results of this study shows that ( %) of adults meet the criteria for the metabolic syndrome. of these, ( %) were women and ( %) men. % of patients in age group of - years meets the criteria for the metabolic syndrome. % of patients - years old, and % of patients ages and older, meets the criteria for the metabolic syndrome. out of the total number of female patients who meet the criteria for the metabolic syndrome, % had increased and % had normal bmi. from the male patients who met the criteria for metabolic syndrome, % had increased, and % had normal bmi.conclusion: the incidence of the metabolic syndrome in family medicine is high. metabolic syndrome is prevalent and significantly increased with age and bmi. more effective interventions in primary care are needed in order to reduce cardiovascular morbidity and mortality. methods: after weeks of high-fat diet, dio mice (n = ) were divided into two groups received either intraperitoneal (ip) injection of ts ( mg/kg, daily) or saline for days. another group of mice were fed low-fat diet (lf) as control (n = ). then both dio mice and lf mice were given intracerebroventricular (i.c.v.) injection of leptin or saline. results: ts significantly decreased final body weight gain (À %, p < . ) and average ei (À %, p < . ) in dio mice. ts significantly decreased pro-inflammatory markers (tnf-a, il- , il- β, p-ikk and p-ijba) in epididymal fat, liver and hypothalamus of dio mice. in lf mice, i.c.v. injection of leptin significantly suppressed ei compared to saline injection (À %, p = . ). however, central leptin sensitivity was blunted in dio mice evidenced aim: non-alcoholic fatty liver disease (nafld), which is characterized by the accumulation of fat in the liver in the absence of alcohol intake, strongly linked to metabolic syndrome. recently, proinflammatory cytokines and oxidative stress mechanisms have been implicated in the pathogenesis of psychiatric disorders. in addition, patients with drug-free schizophrenia have significantly higher body mass index than in aged-matched healthy controls. the purpose of the study was to investigate the effects of metabolic syndrome on the apomorphine-induced stereotypy in a rat model of nafld.materials and methods: eighteen male sprague-dawley rats were included in the study. in order to develop nafld model, rats (n = ) were provided with drinking water containing with % fructose for weeks, while control group (n = ) received only tap water. after the verification of fatty liver by ultrasonography, apomorphine-induced stereotypy was investigated as described by kenneth and kenneth ( ) . then, all rats were sacrificed; homovanillic acid (hva), a dopamine metabolite, levels were measured in brain homogenates. prefrontal cortical il- immunoexpression was evaluated by immunohistochemistry and hepatocellular changes were determined histologically.results: histological evaluation of liver sections confirmed macrovesicular steatosis in nafld rats. moreover, the stereotyped behavior scores, brain hva levels and il- expression were found significantly higher in nafld group than in the control group (p < . ). our results suggest that metabolic syndrome and fatty liver significantly induce dopaminergic activity and stereotyped behavior in rats. the neuromodulatory effects of pro-inflammatory cytokines and imbalance between oxidative and anti-oxidative status may underlie these alterations. the classical thinking in type diabetes is that the plasma glucose levels are regulated by interplay between insulin, glucagon and other peripheral mechanisms. a combination of insulin resistance and relative insulin insufficiency is considered to be causal to hyperglycemia. this traditional wisdom is now being challenged and an alternative model is proposed where the central nervous system (cns) plays a vital role in plasma glucose regulation. the role of cns in glucose regulation is well known. for example it has been shown that intracerebroventricular injection of glucose results in a decrease in plasma glucose level in rats. however whether and to what extent the cns has an active role in diabetic hyperglycemia is not known. we make mathematical models of different versions of the peripheral and central mechanisms and make differential correlational predictions which can be tested on oral glucose tolerance test ( background and aims: high calorie diets leads to fat liver and changes in the metabolic pathways. therefore the gluconeogenic capacity of the livers in a condition of high levels of exogenous fatty acids was evaluated in cafeteria-fed rats.methods: two groups of weaned wistar rats received cafeteria or balanced diet during days. the fasted livers were perfused with mmol/l lactate plus . mmol/l pyruvate in absence or in presence of mmol/l stearate plus traces of [ - c]-stearate. measured parameters: glucose, ketone bodies, [ c]co , oxygen uptake, hepatic contents of lipids and glycogen.results: cafeteria-fed rats presented increase in: body and liver weight, fat in the tissues and hepatic glycogen. perfusion experiments revealed that in cafeteria-fed rats the gluconeogenic flux was lower than in the control, but the infusion of stearate, caused a higher stimulus on glucose production. the co and ketone bodies production was reduced during the active gluconeogenesis in cafeteriafed and control rats, being the former less sensitive, whereas no differences were found after stearate infusion. background: despite advances in option of treatement diabetes, optimal glycemic control is not often achieved. glucose homeostasis is dependent on a complex interplay of multiple hormones and glucagon like peptide- (glp- ) receptor agonists are a new class of drug for the treatment of type diabetes. they are not considered as initial therapy for the majority of patient with type diabetes and their clinical use, long-term benefits, risks and their role in combination with other diabetes medication are still under investigation.study: in the retrospective study in we enrolled patients with poorly controlled type diabetes on one or two oral agents, who received additional therapy with glp- receptor agonist: liraglutide or exenatide. we monitored hba c value and body weight before and after modification of therapy.results: fifty-one patients, men, were - years old (mean years). their mean body weight was . kg (sd ae . ) and mean hba c . % (sd ae ). after - months of combined therapy with metformin and/or sulfonylurea and glp- agonist their mean hba c dropped to . % (sd ae . ) and their body weight reduced to . kg (sd ae . ). in patients with type diabetes and suboptimal control on one or two oral agents adding glp- receptor agonist was effective in improving glycemic control and body weight reduction. despite lack of evidence on their clinical use, long-term benefits and side effects these agents have the potential to change the diabetes treatment by replacing traditional secretagogues because of superior control and association with weight loss. objective: the metabolic syndrome (ms) is a particular affection that has been associated with so many factors such as hypertention. both increase cardiovascular diseases. due to the higher prevalence of hypertension in our country, this study aim to determine the frequency of ms in newly diagnosed hypertensive patients in oder to improve the follow -up of these subjets.methodology: over a period of months, we conducted a crosssectional and descriptive study on patients recently diagnosed as hypertensive for < months. the selection of patients was done during external consultation in the cardiology unit at the university teaching hospital of yaounde. it was based on high blood pressure, anthropome´tric parameters such as weight, bmi, waist, abdominal circonference and biological values (lipid profile, blood glucose, uric acid). we identified patients aged between and years, with a mean age of years. people aged more than years were mostly affected. stage was the prominent stage of hypertension.the prevalence of metabolic syndrome was . % with a higher rate in female.the cardiovascular risk factors were obesity, alcoholism, sedentarity and hypo hdlc factors differenciating population with metabolic syndrom was obesity (p = . ), hyperglycemia (p = . ), hypo hdlc (p = . ) while the phenotypes most represented were hyperglycemia, abdominal obesity and hypo hdlc respectively. the metabolic syndrome is frequent in newly diagnosed hypertensive subjects; the females were most affected. metabolic syndrome should be investigated systematically in all hypetensive patients. background: although mainly inhibits osteoclastogenesis, osteoprotegerin is produced by vasculature too. serum opg (sopg) is elevated in both diabetics and patients with coronary artery disease (cad) but there are still insufficient data for its concentrations in impaired glucose tolerance (igt) subjects. aims: to determine sopg in males with igt and concomitant cad and to investigate its relationship with certain glucometabolic parameters.materials and methods: sopg was measured in males with performed percutaneous coronary interventions for cad- with igt and normoglycemic, and in age-and bmi-matched healthy normoglycemic controls. glucose abnormalities were screen-detected using a standard ogtt. mean intima-media thickness (imt) of common carotid arteries was measured by b-mode ultrasonography. opg was measured by elisa.results: sopg was significantly higher in igt patients compared to controls ( . ae . vs. . ae . pmol/l; p = . ) but did not differ between igt and normoglycemic cad patiens ( . ae . vs. . ae . pmol/l, p = . ). in all participants, sopg correlated positively with imt (p . ; pr . ). similarly, in igt males with cad, sopg correlated only with imt (p . ; pr . ). there were no associations with fasting and postchallange plasma glucose, hba c, fasting insulin, homa-ir, lipid parameters, blood pressure, bmi or waist circumference. we found higher sopg in males with igt and cad compared to the controls. opg did not correlate with glucose parameters but rather with markers of atherosclerosis. we speculate in cad patients with igt, the increased sopg might reflect the vascular damage and not glycemic status which requires further investigations. internal medicine, umf iuliu hatieganu cluj-napoca, cluj-napoca, umf 'victor babes' timisoara, timisoara, romania objective: the pro ala polymorphism in the pparg gene (c>g) is associated with less weight loss after treatment for obesity. this study aimed to investigate the association of rs polymorphism with weight loss year after bariatric surgery. the sample was composed of individuals with grade iii obesity undergoing roux-en y gastric bypass. anthropometric data were collected in the preoperative period and year after surgery. genotyping was performed by the method of allelic discrimination in real time pcr (polymerase chain reaction) using the taqman predesigned snp genotyping assays kits (applied biosystems, foster city, ca, usa). individuals with at least one variant allele were grouped and compared with those with the reference genotype.results: subjects ( . % females, mean age . ae . years) participated in the study. genotyping showed % (n = ) of individuals homozygous for the c allele (c/c) and % (n = ) heterozygous (c/g). there was no homozygous mutant (g/g). individuals with the c/c and c/g genotypes respectively showed a loss of . ae . and ae . kg; . ae and . ae . % of initial weight and . ae and . ae . % of excess body weight. there was no difference in weight loss between groups.conclusion: the pparg pro ala genotype seems to have no association with weight loss year after bariatric surgery. objective: evaluated determine the prevalence of ir, ms and associated factors among banking workers in southeastern brazil.methods: out of males and females banking employees, years old were evaluated by cross-sectional study including demographic, biochemical, anthropometric and hemodynamic. the ms was determinate by ncep and idf. the ir was determined by homa-ir, with the cut off > . .results: ( . % % ci . - . ) and ( . % % ci . - . ) of employees with ms, according to the ncep and idf, respectively and ( . %) with ri. the likelihood of developing the syndrome is greater in individuals with high level of education (or . ( % ci . - . ) and among those with overweight and obesity, the possibility of having ms is , ( % ci . - . , p = . ) and . ( % ci . - . , p = . ) times over, respectively. persons who are overweight are at risk of . ( % ci . - . ) times more likely to have elevated homa, and among those who are obese, the risk rises to . ( % ci . - . ).conclusion: this study showed the higher number of employees who have similar characteristics of the total active working, that despite high education, also have ms and ir, and the consequent risk of developing cardiovascular disease. prediabetes is considered as a strong risk factor for type diabetes (dm ). tcf l is a gen involved in dm susceptibility related with glp-l. objective: study the relationship of rs and rs variants of the tcf l gene with insulin levels, c-peptide and glp- in normoglycemia and prediabetes subjects. we included pre-diabetic and normoglycemic subjects. we measure fasting glucose, lipids, insulin, c-peptide and glp- ). insulin resistance and beta-cell function were calculated with the homa model. tcf l polymorphisms rs c/t and rs g/t were determined by pcr-rflp. for analyses two groups were compared: wild-type and carriers of two allele risk. we included a total of subjects aged ae years. weight, bmi, systolic and diastolic blood pressure and triglycerides were significantly lower in the group of healthy subjects. glp- was higher in normoglycemic subjects. the frequency of rs t allele was higher in pre-diabetic subjects, while the allele frequency of rs t was not significantly different between the groups. in carriers of rs t, serum insulin and homa-beta were significantly higher. plasma levels of glp- were lower in prediabetic subjects with and without the risk allele variant. in prediabetic subjects carriers of the rs g/t or tt had also lower levels of serum insulin, homa-ir and homa-beta. the glp- concentrations were lower in both groups.conclusions: in this work the rs polymorphism tcf l gene was associated with prediabetes. the frequency of the rs t allele tcf l gene was not different between groups. objective: determine hba c, igfbp , fgf and other metabolic markers in non-diabetic, prediabetic, type diabetics (t dm) of recent diagnosis. material and methods: a cross-sectional population based study was carried in - years old subjects classified with fasting glucose (fg) and after h g oral glucose load (gt), as normal with impaired fg (ifg), impaired gt (igt), with both alterations (ifg/igt) and dm . after - weeks subjects were re-classified and registration of anthropometric data, food intake and determination of a c, lipids, insulin, fgf and igfbp .results: we found . % for prediabetes and . % for dm (n = ). in the re-classification we classified: normal, ifg, igt, ifg/igt, dm . with anova analysis we found that hba c in dm patients was different from normal, ifg, ifg/igt subjects (p < . , p < . and p < . respectively). fgf levels was different among all groups (p < . ). normoglycemic subjects were better educated and had higher income than the prediabetic and dm subjects. dm subjects reported more screen time. prediabetic subjects had higher hdl-cholesterol. with multiple regression analysis we found igfbp positively correlated with daily caloric intake and triglycerides and negatively with bmi. the fgf correlated positively with insulin. the prevalence of pre-diabetes is more than twice of that of undiagnosed diabetes. we find fgf and insulin related with the metabolic status. igfbp was negatively correlation with bmi finding compatible with an association with insulin resistance. we have previously found that the expressions of several homeobox transcription factors, including irx , were reduced in subcutaneous fat in human obesity. a knock-out (ko) mouse line was acquired for the purpose of investigating the in vivo effects of irx deficiency with the main perspective on how these mice would handle a high-energy dietary intake. though initially undersized, male irx ko mice fed a high-fat ( %) diet approached similar weight and size as their wildtype (wt) littermates. yet, mri show that the irx ko mice have smaller adipose tissue depots and store less fat around organs in aim: to examine the role of mir- in the pathogenesis of diabetic cardiomyopathy.objectives: to study the cardiac expression of mir- and its effect on regulation of genes involved in akt-pkb signalling pathway in animal model of diabetic cardiomyopathy (dcm).methods: type diabetes was induced in adult wistar rats by high fat diet and i.p streptozotocin injections. the animals were sacrificed at weeks and development of cardiomyopathy was confirmed by heart/body weight ratio, histopathological examination, myocardial fibrotic and hypertrophic genes. cardiac tissues were examined for expression of mir- , its target genes by real time pcr.results: myocardial expression of mir- was significantly increased and showed a positive correlation with myocardial mrna levels of fibrotic genes (ctgf, fgf-b & tgf-b) in diabetic rats. myocardial mrna levels of potential targets of mir- , phosphatase and tensin homolog deleted on chromosome (pten) and programmed cell death protein (pdcd- ), were increased and their protein expression was decreased in dcm group and in fibroblasts exposed to high glucose (p < . ). increasing mir- levels promoted, whereas knocking down mir- attenuated, pten, pcdc- activity in cardiac fibroblasts. our results suggest that mir- contributes to cardiac fibrosis in dcm by modulating activity of akt/pkb pathway through pten and pcdc- . objectives: many studies have revealed that prevalence of metabolic syndrome may be related to lifestyle components. the aim of this study was to investigate the influence of dietary patterns on prevalence of metabolic syndrome (mets). the data was based on health and nutrition survey for japanese men and women aged - year. factor analysis was used to obtain dietary patterns applying to intake of food groups. the definition of mets was followed by the modified version of the criteria of idf that is applied to japanese population. values of waist circumference, hdl-cholesterol, blood pressures, and hba c were used to identify mets. logistic regression analysis was used to examine the association between dietary patterns and prevalence of mets.results: three dietary patterns of "fruits", "rice", and "meat" were identified. in males, greater values of "fruits" pattern was associated with a significantly lower prevalence of mets after adjustment for age, physical activity level, smoking and drinking status and other confounding variables (or = . , % ci . - . ).conclusions: fruits consumption was inversely associated with mets and this association may be explained by much intake of mandarin orange specific to this surveyed population. this finding necessitates further investigation on the mechanisms of fruits consumption on health benefits. introduction: the impaired glucose regulation shows a double risk of cardiovascular morbimortality and development of type diabetes, especially in patients with high cardiovascular risk.objective: identify the carbohydrate abnormalities in unknown diabetic patients with high cardiovascular risk.patients and methods: hundred and forty-eight non-diabetic patients were involved in this single-center study, with at least three known vascular risk factors, metabolic syndrome or with known cardiovascular event over months.all had a test load of g oral glucose (ogtt) followed by h after dosing plasma glucose, serum glycated hemoglobin (hba c) and lipid abnormalities exploration. cardiovascular exploration also concerned all patients.results: among these patients, were in primary prevention and in secondary prevention. cardiovascular events were reported to be dominated by myocardial infarction ( . %) and stroke ( . %).dysglucoregulation concerned patients ( %); the sex ratio was . and the average age was , . unknown diabetes, ifg and igt were diagnosed.these glucose abnormalities were found equally in both primary and secondary prevention.in the family, diabetes was concerned with % and cardiovascular events mainly expressed by early myocardial infarction and stroke were observed in %.the vascular risk factors were more present in igt group.hypertension was found in %, followed by dyslipidemia in %; % met metabolic syndrom's criteria (idf ) .conclusion: in primary prevention context, ogtt not only detects unknown diabetics but identifies igt patients who dysplay a high risk of cardiovascular events. the aim was to study some indicators of inflammatory process and oxidative metabolism in the patients arriving for surgical treatment of pathological obesity. laboratory tests have been carried out by conventional methods in patients with pathological obesity of abdominal type with a body mass index > kg/m before and after biliopancreatic shunting operation.rise of blood glucose level up to . % (p < . ), uric acid level up to . % (p < . ), as well as dyslipidemia were determined in patients. the content of malondialdehyde (mda) increased . times, the general antioxidant activity (aoa) decreased . times. concentration of c-reactive protein (crp) exceeded . times the control value. the long-term results in these patients within - months have shown normalisation of level of blood glucose, uric acid, high and very low density lipoprotein cholesterol, a tendency of decrease in the general cholesterol concentration. triglycerides decreased by %, still remaining at sufficiently high level. mda concentration decreased by . %, aoa increased by . %. crp level which was considerably raised before operation decreased within the next months but in months its average value increased five times in relation to normal rate.the obtained results are evidence of the interrelation of inflammation process and oxidative stress in patients with pathological obesity and metabolic syndrome. efficiency of surgical treatment was shown in the insulin resistance syndrome includes well-recognized cardiovascular risk factors such as low hdl levels, hypertension, hypertriglyceridemia, which is highly correlated with small dense ldl and increased lp(a) levels, which is cardiovascular risk factor. we aimed to study dyslipidemia, especially lp(a) level in addition to carotid intima media thickness (ca-imt) as a marker of atherosclerosis in normal and impaired glucose tolerance offspring of type dm. subjects were included and divided into two main groups; group(i) apparently healthy subjects with no family history of diabetes mellitus, as control group, group(iia) non diabetic offspring of type dm with normal glucose tolerance and group(iib) non diabetic offspring of type dm with impaired glucose tolerance. a statistically significant increase in mean ae sd of serum level of lp(a) and ca-imt in non diabetic impaired glucose tolerant offspring of type diabetes as compared to non diabetic normal glucose tolerant group, significant positive correlation between lp(a) and ca-imt vs. each of ldl-ch, triglycerides and cholesterol. also, a significant positive correlation between lp(a) and ca-imt and hdl-ch. in non diabetic impaired glucose tolerant offspring of type diabetes as compared to non diabetic normal glucose tolerant group. in conclusion the increase in serum level of lp(a) and increase of ca-imt in non diabetic offspring of type dm were associated with increasing severity of insulin resistance and increasing the degree of atherosclerosis explaining the high prevalence of cardiovascular diseases in subjects who are genetically prone to the development of diabetes. a. kostrzewa-tarnowska, m. człapka-matyasik, m. fejfer, j. jeszka weight loss can be achieved by any means of energy restriction, but the challenge is to achieve sustainable weight loss and prevent from weight gain without increasing the risk of chronic diseases. conventional high carbohydrate diets, even when based on wholegrain foods, increase insulinemia and may compromise weight control via mechanisms related to appetite stimulation and metabolic rate. the success of low fat diets has given a push for researches on alternative dietary strategies, including high content of bioactive compounds and low glycemic index (gi) diets.the aim of this study was to determine if high content of bioactive compounds using capillary blood sampling lead to any significant difference between the gis of the products mentioned. investigated group consisted of healthy people with normal weight, aged ae years (bmi . ae . kg/m ).foods with a low gi produce a lower peak in postprandial glucose and a less overall blood glucose increase during the first h after consumption compared with foods with a high gi. studies have shown that bioactive products lead to increased satiety, delayed return of hunger, and decreased food intake after ingestion of low-gi compared with high-gi foods.low-gi products may also play an extensive role in weight loss. this strategy can be associated with reducing total energy intake, modifying the macronutrient composition of the diet and lower postprandial glycaemia.research funded within the framework of the project po ig . . . - / . physiology, school of medicine, national university of ireland, galway, ireland introduction: current diagnostic criteria for type diabetes mellitus rely on increased blood glucose concentration following an oral glucose tolerance test (ogtt) or increased glycated haemoglobin. changes in these parameters occur long after insulin resistance manifests as plasma glucose concentration is homeostatically defended. in contrast, glucose oxidation measured by the c-glucose breath test ( c-gbt) is reduced as a direct consequence of insulin resistance. it is important to establish normative data and define the reliability of any diagnostic or scientific test therefore the aim of this study was to determine the reliability of the c-gbt as a diagnostic tool for type diabetes.methods: sixteen apparently-healthy controls { . ( . ) yrs, . ( . ) kg, . ( . ) cm, all data mean (sd)} underwent simultaneous ogtt and c-gbt on two separate occasions following a h overnight fast. mixed capillary blood and breath samples were collected at baseline and every min for h following ingestion of a . g glucose solution (shamrock, ireland) labelled with . g - c glucose.results: mean baseline co was . ae . delta viennapeedeebelemnite (d-vpdb) and peak co was À . ae . d-vpdb. fasting and h mixed capillary glucose concentrations were . ae . mmol/l and . ae . mmol/l respectively. per cent dose recovered c had a cronbach's alpha of . , while fasting and h glucose concentration were . and . respectively. we established normative data for the c-gbt. the c-gbt is a reliable test of whole body glucose oxidation which has the potential to be developed as a diabetes diagnostic test. introduction: outcome studies in morbidly obese patients (mo) have shown that diabetic patients have the highest benefit from bariatric surgery interventions. therefore it was of interest to study a variety of cardiovascular risk factors in a very large group of patients with mo (n = ), who were investigated in our center. we included patients with mo, of whom . % (n = ; mean hba c . ae . %) were diabetic. in a subset (n = ), patients were followed up years after bariatric surgery of whom . % (n = ) were diabetic. all patients without manifest type diabetes underwent a g oral glucose tolerance test, insulin levels were assessed, homa-insulin resistance (ir) was calculated. diabetes was diagnosed after ada criteria. apart from that demographic, cardiovascular risk-markers (blood pressure, lipids) renal and inflammation parameters were assessed. background: obex â is a dietary supplement to help lose weight. in addition, this supplement is specifically made with natural antioxidants molecularly activated to enhance their biological properties without altering their molecular structure.objectives: the purpose of this study was to evaluate the effect of obex â on anthropometric measurements and metabolic disorders in overweight and obese subjects. this was an open label pilot study conducted with overweight and obese adults (bmi > kg/m and < kg/m ), aged between and , who took obex â (without changes in lifestyle), at a dose of two sachets before the two main meals of each day for months. in addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, creatinine and uric acid were determined. insulin resistance by homa-ir and betacell function by homa-b were assessed. three indirect indexes were used to calculate insulin sensitivity.results: compared to baseline, obex â significantly reduced body weight (p = . ), body mass index, waist circumference, waist/hip ratio, waist/height ratio (p < . , respectively) and conicity index (p = . ). there was also a reduction in fasting glucose levels. compared to baseline, the use of obex â improved insulin secretion (homa-b) and hdl-c concentration (p < . ). no adverse effects were seen in any of the participants during the pilot study.conclusion: short-term treatment with obex â improved visceral and abdominal obesity, as well as ameliorating levels of select markers of metabolic disease risk in overweight and obese adults, indicating that further studies are warranted. methodology: a descriptive cross sectional study was conducted with families. the sample was family members (partner, offspring, blood family members and not family related individuals-all living in the same house). body mass index (bmi), lipid profile and glucose measured. also, the family functionality (ff) and perceived health status (phs). results: age mean was . years (sd, . ); female ( . %) and males ( . %). the rf were analyzed by the role in the family. seventy-five percent of the housewives were overweight, with high levels of glucose ( . %), cholesterol ( . %), triglyceride ( . %) and low hdl ( . %). husbands had overweight ( %), with high levels of glucose ( . %), cholesterol ( . %), and triglyceride ( . %). the children aged between and years, had glucose and cholesterol normal, but were overweight ( . %), and had high level of triglyceride ( . %) as well as low hdl ( . %). additionally, children and parents had only - portions of vegetables intake in - days in week; similarly . , had - portions of fruits or juice, but only - days by month. family functionality was reported with a mean of . (sd, . )- - scale and . (sd, . ) in phs. the family members in the ua are at high risk for developing dt . among them are underscored obesity, high levels of lipids, low consumption of vegetables and fresh fruits. ff and phs are also risk factors in these families. this study designed to compare the effect of three dietary oils: canola, rice bran and grape seed on lipid profile and paraoxanase activity of hyperlipidermic rats. method: hyperlipidemia was induced in wistar male rats by atherogenic diet. once hyperlipidemia was reached, the rats were randomly divided in four groups of animals according to the treatment received. treatment groups were fed canola, rice bran and grape seed oil for weeks. control rats fed regular rat chow diet which contains corn oil. baseline fasting blood lipid profile and paraxonase activity of experimental and control rats were compared at the beginning and at the end of the experiment.result: after -weeks of treatment, a significant decrease was found in serum triglyceride, total cholesterol and ldl-c concentration of rice bran and grape seed oil fed rats (p < . ), serum hdl-c concentration also increased significantly (p < . ). canola oil fed rats showed a significant decrease in total cholesterol, and triglyceride level and an increase in paraoxanase activity (p < . ), however, no significant differences were found in ldl-c and hdl-c concentration. the present study suggest that consumption grape seed, canola and rice bran oil may have beneficial effect on serum lipid profile, but in comparison of the tree dietary oils grape seed oil showed more beneficial effect in reducing hyperlipidemia.