Early pregnancy meal tolerance test responses and their association with later insulin sensitivity in overweight and obese women: an exploratory analysis

Introduction: Insulin resistance increases the risk for gestational diabetes mellitus (GDM) and hyperglycemia-associated pregnancy complications. GDM is generally diagnosed at 24-28 weeks of gestation, leaving limited time to address adverse consequences. To explore metabolic markers that predict changes in insulin sensitivity and glycemic responses earlier in pregnancy, we performed a meal tolerance test (MTT) during the early and late second trimester in an at-risk population. Methods: We included 30 pregnant women with overweight or obesity in the Pregnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study. Glucose, insulin, and C-peptide levels were measured in fasted and post-challenge blood samples between week 12-16 (MTT1, n=26), week 24-25 (MTT2, n=21), and by an oral glucose tolerance test in week 26-27 (OGTT, n=19) of gestation. Pearson's correlation test, Spearman's correlation test, and linear regression were applied to evaluate the association between parameters at early and late time points. Results: Fasting insulin and C-peptide at MTT1 were associated with insulin resistance measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) later in pregnancy (r=0.752, p