Towards Precision Medicine in Gestational Diabetes: Pathophysiology and Glycemic Patterns in Pregnant Women With Obesity

Precision medicine has revolutionised our understanding of type 1 diabetes and neonatal diabetes, but has yet to improve insight into gestational diabetes (GDM), the most common obstetric complication, and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1h, 2h) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles.867 pregnant women with obesity (BMI > 30kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks' gestation (75g oral glucose tolerance test OGTT; WHO criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analysed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterised by HOMA2b and HOMA2s respectively.In women who developed GDM (n=241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics, and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycaemia had comparable insulin secretion and sensitivity to euglycaemic women potentially indicative of a novel mechanistic pathway.Patterns of glycaemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycaemia reflects a different mechanistic pathway for targeted management.