Pronounced Insulin Resistance and Inadequate β-cell Secretion Characterize Lean Gestational Diabetes During and After Pregnancy
- Alexandra Kautzky-Willer, MD,
- Rudolf Prager, MD,
- Werner Waldhäusl, MD,
- Giovanni Pacini, PHD,
- Karl Thomaseth, PHD,
- Oswald F Wagner, MD,
- Martin Ulm, MD,
- Carola Streli, MD and
- Bernhard Ludvik, MD
- Department of Medicine III, University of Vienna Austria
- Division of Endocrinology and Metabolism, Department of Obstetrics and Gynecology, University of Vienna Austria
- Institute of Systems Science and Biomedical Engineering (LADSEB-CNR) Padova, Italy
- Address correspondence and reprint requests to Bernhard Ludvik, MD, Department of Medicine III, Division of Endocrinology and Metabolism, University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
Abstract
OBJECTIVE To evaluate β-cell secretion and glucose metabolism in lean subjects with gestational diabetes mellitus (GDM) compared with that in subjects with normal pregnancy and obesity.
RESEARCH DESIGN AND METHODS Insulin secretion, insulin sensitivity (S1), and hepatic insulin extraction were assessed in pregnant women with GDM before and after delivery and in those with normal glucose tolerance (NGT) in comparison to healthy nonpregnant lean and obese women. Kinetic analysis of glucose, insulin, and C-peptide plasma concentrations during oral and intravenous glucose tolerance tests was performed by mathematical modeling.
RESULTS S1 was blunted in pregnant women with GDM by 84% and in those with NGT by 66% compared with lean nonpregnant women (P < 0.005 vs. healthy nonpregnant lean control subjects; P < 0.05, GDM vs. pregnant women with NGT), whereas glucose effectiveness was decreased by 33% in both pregnant groups (P < 0.05 vs. healthy nonpregnant lean control subjects). Insulin secretion was 30% higher (P < 0.05) in subjects with GDM than in pregnant women with NGT or in nonpregnant lean women, but decreased (P < 0.005) when compared with obese women with a comparable degree of insulin resistance. Fractional hepatic insulin extraction was similar in both pregnant groups, being lower (P < 0.0001) by 30% versus nonpregnant females. β-cell sensitivity to glucose for insulin release was decreased in subjects with GDM versus pregnant women with NGT as well as nonpregnant women by 40-50% (P < 0.01). Twelve weeks after delivery, GDM returned to normal glucose tolerance, but S1 remained 50% lower than that in lean nonpregnant women, while β-cell sensitivity to glucose did not change (P < 0.01 vs. healthy nonpregnant lean control subjects).
CONCLUSIONS Pregnancy is characterized by insulin resistance, diminished hepatic insulin extraction, and glucose effectiveness. Lean subjects with GDM are additionally characterized by having more pronounced insulin resistance and inadequate insulin secretion, which persist after delivery. Compared with other insulin-resistant prediabetic states like impaired glucose tolerance (IGT), defective insulin secretion seems to be a predominant defect in lean GDM subjects, indicating that it might represent a specific prediabetic condition.
- Received November 18, 1997.
- Accepted July 17, 1997.
- Copyright © 1997 by the American Diabetes Association
