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

Abstract

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 β-cell function (i.e., 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 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 β-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, β-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 β-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 β-cell function early during pregnancy and a greater subsequent decline in IS and blunted increase in β-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.

Trial registration: ClinicalTrials.gov NCT01768793.

Graphical abstract

Figure 1

Metabolic profile during the OGTT performed at 15 weeks’ and 35 weeks’ gestation in the GDM group (n = 29) and the No-GDM group (n = 164). A–E: Plasma glucose (A), FFA (B), insulin (C), and C-peptide (D) concentrations, and ISR (E) immediately before and for 1 h after ingesting 75 g of glucose. F: ISR in relation to plasma glucose concentration, a measure of β-cell responsiveness to glucose, during the first 30 min of the OGTT. Values are mean ± SEM. Some error bars are smaller than the symbols and, therefore, are not visible.

Figure 2

ROC for predictors of GDM. Colored lines represent the following: fasting plasma glucose concentration at 15 weeks (blue line) (AUC: 0.68; P = 0.001); 1-h plasma glucose concentration during the OGTT at 15 weeks (red line) (AUC: 0.71; P = 0.002); glucose concentration AUC between 0 and 120 min during the OGTT at 15 weeks (green line) (AUC: 0.70; P = 0.001); and reference line that indicates no predictive power (orange line).