Recommended pre‐analytical plasma glucose sampling methodology may distort gestational diabetes mellitus prevalence: implications for diagnostic thresholds

Abstract

Aim Current International Association of the Diabetes and Pregnancy Study Groups/World Health Organization gestational diabetes mellitus (GDM) diagnostic thresholds are based on a landmark study in which the pre-analytical plasma glucose sampling methodology is unclear. Worldwide, plasma glucose pre-analytical sampling methodology practices are divergent. We considered the effects of pre-analytical plasma glucose sampling methodology on GDM prevalence and gestational outcomes.Methods This is a retrospective observational cohort study of 1178 pregnant women undergoing an oral glucose tolerance test (OGTT). Of the 1178 pregnant women, a subset of 892 non-GDM women with singleton births undergoing OGTT between 24 and 28 weeks' gestation were investigated for large for gestation age (LGA) outcomes. OGTT were determined using traditional methods (sodium fluoride tubes batched at roomed temperature). We modelled the potential effects of using a recommended pre-analytical plasma glucose methodology (lyophilized citrate tubes) on GDM prevalence. ResultsThe GDM prevalence in our cohort was 13.5%. The incidence of LGA showed a linear association with maternal plasma glucose that was similar to the association observed in the Hyperglycemia and Adverse Pregnancy Outcome study. Frequency of LGA exceeded 10% at HAPO glucose category 4 (fasting, 4.8 to 4.9 mmol/l; 1-h, 8.7 to 9.5 mmol/l) for fasting and 1-h plasma glucose. The use of a recommended pre-analytical method is projected to increase the prevalence of GDM to 39.2%. ConclusionWe challenge the consensus that recommended pre-analytical plasma glucose methodologies are optimal for the accurate diagnosis of GDM. Recommended pre-analytical plasma glucose methods may profoundly overdiagnose GDM. Centres using recommended pre-analytical plasma glucose methodologies may need to reappraise their diagnostic thresholds.

Learning about diabetes through epidemiology

“…Although well recognized in the biochemical research literature, one important issue that is too rarely discussed is the type of sample and the handling of samples before the assay of glucose or HbA 1c . The current recommendations and thresholds for diagnosing gestational diabetes are based on the HAPO study where the pre‐analytical sampling methodology was ‘left to the discretion of local sites’ . In some settings, it is likely that the pre‐analytical sampling methodology in the HAPO study did not prevent glycolysis, which could render the levels of these current diagnostic recommendations too low.…”

“…Song et al . studied 892 pregnant women, of whom 14% had gestational diabetes, using samples collected in sodium fluoride/potassium oxalate tubes, stored at room temperature . Using lyophilized citrate tubes reduces glycolysis and so measurements are higher than samples using sodium fluoride/potassium oxalate tubes stored for a similar time.…”

Estimated Treatment Effects of Tight Glycaemic Targets in Mild Gestational Diabetes Mellitus: A Multiple Cut-Off Regression Discontinuity Study Design

“…To further categorise patients, all were given a Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) glucose composite score. Each patient was categorized according to HAPO glucose categories [13]:…”

“…The range of fasting plasma glucose levels in a population was narrower than the 1 h and 2 h levels, each patient's OGTT results were scaled according to a measure with equivalent risks of adverse outcomes-the HAPO study's glucose categories (between 1 to 7) [13]. The HAPO glucose composite score for each patient was the sum of scores of maternal plasma glucose exposure at each OGTT time point.…”

Estimated treatment effects of tight glycaemic targets in mild gestational diabetes mellitus: a multiple cut-off regression discontinuity study design.

“…Our OGTTs were collected using sodium fluoride collected at room temperature and batched centrifuged 10 . This pre-analytical method has been recently documented, via the process of glycolysis, to lower reported OGTT fasting glucose levels by approximately 10% 10,23 . Therefore the adjusted lower and upper reference level of fasting glucose should be 10% higher -approximately 4.1 to 5.8 mmol/L.…”