Insulin Sensitivity and β-Cell Function During Early and Late Pregnancy in Women With and Without Gestational Diabetes Mellitus

OBJECTIVE To evaluate the metabolic alterations associated with gestational diabetes mellitus (GDM) in women with overweight or obesity. RESEARCH DESIGN AND METHODS We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrations, insulin sensitivity (IS; Matsuda index), and beta-cell function (i.e., beta-cell responsiveness to glucose) by using a frequently sampled oral glucose tolerance test (OGTT) at 15 and 35 weeks' gestation in women with overweight or obesity who had GDM (n = 29) or did not have GDM (No-GDM; n = 164) at 35 weeks. RESULTS At 15 weeks, IS and beta-cell function were lower, and fasting, 1-h, and total area-under-the-curve plasma glucose concentrations during the OGTT were higher (all P < 0.05) in the GDM than in the No-GDM group. At 35 weeks compared with 15 weeks, IS decreased, beta-cell function increased, and postprandial suppression of plasma FFA was blunted in both the GDM and No-GDM groups, but the decrease in IS and the increase in postprandial FFA concentration were greater and the increase in beta-cell function was less (all P <= 0.05) in the GDM than in the No-GDM group. A receiver operating characteristic curve analysis showed that both fasting plasma glucose and 1-h OGTT glucose concentration at 15 weeks are predictors of GDM, but the predictive power was <30%. CONCLUSIONS Women with overweight or obesity and GDM, compared with those without GDM, have worse IS and beta-cell function early during pregnancy and a greater subsequent decline in IS and blunted increase in beta-cell function. Increased fasting and 1-h OGTT plasma glucose concentration early during pregnancy are markers of increased GDM risk, albeit with weak predictive power.