Insulin Sensitivity and Beta-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/obesity.

Methods: We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrations, insulin sensitivity (Matsuda index), and β-cell function (β-cell responsiveness to glucose) by using a frequently-sampled oral glucose tolerance test (OGTT) at 15 and 35 weeks’ gestation in women with overweight/obesity who had GDM (n=29) or did not have GDM (n=164) at 35 weeks.

Results: At 15 weeks, insulin sensitivity and β-cell function were lower and fasting, 1-hour and total area-under-the-curve plasma glucose during the OGTT were higher (all P<0.05) in the GDM than in the No-GDM group. At 35 compared with 15 weeks, insulin sensitivity decreased, β-cell function increased, and postprandial suppression of plasma FFA was blunted in both the GDM and No-GDM groups, but the decrease in insulin sensitivity and the increase in postprandial FFA concentration were greater and the increase in β-cell function was less (all P≤0.05) in the GDM than in the No-GDM group. A receiver-operating-curve analysis showed both fasting plasma glucose and 1-hour OGTT glucose at 15 weeks are predictors of GDM, but the predictive power was <30%.

Conclusion: Women with overweight/obesity and GDM, compared to those without GDM, have worse insulin sensitivity and β-cell function early during pregnancy and a greater subsequent decline in insulin sensitivity and blunted increase in β-cell function. Increased fasting and 1-hour OGTT plasma glucose early during pregnancy are markers of increased GDM risk, albeit with weak predictive power.