key: cord-0859397-mm9udo0g
authors: Choy, Kay W.
title: Diagnostic testing for gestational diabetes mellitus during the COVID‐19 pandemic: an opportunity to revisit glucose‐based testing
date: 2020-07-12
journal: Intern Med J
DOI: 10.1111/imj.14902
sha: 79c67b92ddcc189cda7817eb8236945d2a7fbef8
doc_id: 859397
cord_uid: mm9udo0g

nan

Diagnostic testing for gestational diabetes mellitus during the COVID-19 pandemic: an opportunity to revisit glucose-based testing Advice on diagnostic testing for gestational diabetes mellitus (GDM) during the COVID-19 pandemic was recently provided by the Australasian Diabetes in Pregnancy Society and the Australian Diabetes Society. 1 For women at low risk for GDM, an alternative method of testing for GDM involves an initial fasting blood glucose (FBG) and subsequent oral glucose tolerance test (OGTT) (75 g oral glucose load) for women with FBG 4.7-5.0 mmol/L; FBG of >5.0 mmol/L is diagnostic of GDM. OGTT is not indicated if FBG is <4.7 mmol/L. The pre-analytical and analytical variations for glucosebased testing should be considered. A major source of preanalytical error is loss of glucose from blood specimens through glycolysis. 2 Glucose is lost from whole blood samples at a rate of 5-7% per hour at room temperature. 2 Preanalytical loss of glucose poses a threat to the diagnostic sensitivity of glucose-based testing for GDM. The most commonly used blood collection tube for glucose is sodiumfluoride-based and it is widely used to inhibit glycolysis but it is inadequate. Sodium-fluoride does not stop glycolysis for the first 2 h or more after sample collection, and during the first 60-90 min, the loss of glucose proceeds at the same rate with or without sodium-fluoride. 2 The American Diabetes Association (ADA) guideline on laboratory testing in diabetes recommends that samples be immediately immersed in ice slurry and analysed within 30 min of collection. 2 This is difficult to achieve in routine patient care and is not always followed in GDM testing. The diagnostic criteria for GDM were based on the Hyperglycaemia and Adverse Pregnancy Outcome study, which had strict protocol for glucose sample handling. 2 In a study by Daly et al., implementation of ADA glucose sample handling recommendations resulted in a 2.7-fold increased detection of GDM compared with usual hospital practices. 3 When studying the impact of handling fluoride-oxalate samples at room temperature in rural and remote Australia, Jamieson et al. estimated a 62% underdiagnosis of GDM compared to fluoride-oxalate samples on ice slurry. 4 Fluoride-citrate-EDTA (ethylenediaminetetraacetic acid) tubes virtually inhibit glycolysis and have been recommended to replace sodium-fluoride-containing tubes. 2 However, these tubes are not universally available and the costs are significantly higher.

The biological variations of FBG and OGTT should not be overlooked. Chai et al. examined the impact of within-individual biological variation (CVi) and analytical variation on classification of diabetes in a large non-pregnant population cohort in Singapore. 5 Using numerical simulations, accounting for CVi for FBG (5.7%) and OGTT (16.7%) and analytical variations, they found a potential 14.4% increase in diabetes diagnosis if glucose measurements were repeated for the group with original classification of impaired fasting glucose (World Health Organization criteria). 5 Furthermore, a potential 26.6% increase in diabetes diagnosis was estimated if glucose measurements were repeated for the group with impaired glucose tolerance. The use of the average of results of the repeat laboratory tests appears to improve the consistency of disease classification. 5 The COVID-19 pandemic has led to a revisit of laboratory testing. We should never waste a good crisis. 

Gaucher disease (GD), one of the two most common inherited lysosomal storage disorders, is considered rare, but in the Ashkenazi Jewish population its prevalence is approximately 1:850. 1 GD is an autosomal recessive disease caused by inherited mutations in the GBA1 gene, leading to reduced activity of the lysosomal enzyme glucocerebrosidase and thereby to the accumulation of the glucocerebroside in macrophages in the spleen, liver, bone marrow and lungs. Recently, it has become apparent that chronic inflammation, immune dysregulation, and enhanced activation of the coagulation and fibrinolytic systems all play a part in the pathophysiology of the disease. Accordingly, many secretory products of activated macrophages, such as the pro-inflammatory cytokines interleukin (IL6, IL10) and tumour necrosis factor alpha (TNFα), have been reported in GD. 2 In addition, elevated levels of serum ferritin, D-dimers and soluble macrophage-derived CD163 are rather common in GD and are also markedly elevated in the cytokine storm seen in patients with COVID-19. 3 The current coronavirus pandemic is characterised by high infection rates and higher mortality among the elderly and in patients with some underlying medical conditions, including those with a compromised immune system. This has naturally raised great concerns among many patients with GD, who in addition to the previously listed markers of disease, also have high levels of angiotensin-converting enzyme (ACE), although the correlation with the ACE-2 receptor is not clear. 4 Interestingly, to the best of our knowledge, no serious cases of COVID-19 infections have been reported in GD. Among our cohort of approximately 550 adults from Israel and Australia with GD (median (range), 46 (18-94) years), we have only a single patient (age 24, in her eighth month of pregnancy) with confirmed COVID-19 infection, whose clinical course was mild and short, and was managed by quarantine for 14 days. It is important to emphasise that in both countries, only symptomatic cases were tested for possible COVID-19 infection, thus it is possible that other patients with GD were infected but they were not detected since they were asymptomatic.

As glycosphingolipids may impact the immune system in opposing directions, 5 we speculate that the accumulated glycosphingolipids in patients with GD promote mainly immune tolerance rather than inflammation when exposed to COVID-19, but a final conclusion should await a future report from an international consortium currently organised by the European Working Group of Gaucher disease.

Diagnostic Testing for Gestational Diabetes Mellitus (GDM) During the COVID-19 Pandemic: Antenatal and Postnatal Testing Advice. Sydney: ADIPS [updated