American Diabetes Association
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Insulin Sensitivity and Beta-Cell Function During Early and Late Pregnancy in Women with and without Gestational Diabetes Mellitus

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posted on 2023-06-01, 17:28 authored by Bettina Mittendorfer, Bruce W. Patterson, Debra Haire-Joshu, Alison G. Cahill, W. Todd Cade, Richard I. Stein, Samuel Klein


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.


This study was supported by National Institutes of Health (NIH) grants U01 DK094416, P30 DK056341 (Washington University Nutrition and Obesity Research Center), P30 DK092950 (Washington University Center for Diabetes Translation Research), P30 DK20579 (Washington University Diabetes Research Center) and UL1 TR002345 (Washington University Clinical and Translational Science Award) and was part of the Lifestyle Interventions For Expectant Moms (LIFE-Moms) consortium, which is supported by NIH grants U01 DK094418, U01 DK094463, U01 DK094416, U01 DK094466, U01 HL114344, U01 HL114377, U01 HD072834, the National Center for Complementary and Integrative Health, the NIH Office of Research in Women’s Health, the Office of Behavioral and Social Science Research, the Indian Health Service, and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.