Insulin Resistance and Impaired Insulin Secretion in Subjects with Histories of Gestational Diabetes Mellitus

Abstract

NIDDM is characterized by decreased insulin secretory responses to glucose and to nonglucose stimuli, hyperglucagonemia, and decreased tissue sensitivity to insulin. However, it hasbeen unclear which of these abnormalities, if any, precedes the others. Since women with histories of gestational diabetes mellitus (GDM) are at high risk for eventual development of NIDDM, we measured B- and A-cell function and tissue sensitivity to insulin in eight normoglycemic, postpartum women with recent histories of GDM and in eight control subjects pair-matched for age and percent of ideal body weight. Fasting plasma glucose levels in subjects with former GDM tended to be slightly higher than in matched controls (98 ± 3 versus 92 ± 2 mg/dl, P = 0.07). Basal plasma insulin in subjects with former GDM was significantly higher than in controls (22 ± 4 versus 14 ± 2 μUml, P = 0.05). During an intravenous glucose tolerance test (IVGTT), relative first- and second-phase insulin responses to glucose were decreased in subjects with former GDM (2316 ± 560 versus 7798 ± 1036% of basal · min, P = 0.004; and 8340 ± 946 versus 14,509 ± 2556, P = 0.04). An index of sensitivity to insulin, S1, calculated from the IVGTT, was also lower in former GDM (1.23 ± 0.69 × 10 4 versus 3.58 ± 0.78 × 10−4 min−1μU/ml, P = 0.001). Acute insulin responses to 5 g i.v. arginine were measured at plasma glucose levels of approximately 95, 215, and 600 mg/dl. The response at 600 mg/dl is termed the AIRmax andis used asan index of glucoseregulated insulin secretory capacity. Insulin responses to arginine at all glucose levels were similar in both groups. However, AIRmax, which was inversely correlated with S1 in controls, appeared low for the degree of insulin resistance informer GDM. Glucagon responses to arginine obtained at normoglycemia and suppressibility of such responses by hyperglycemia (600 mg/dl) were similar in both groups. We conclude that women with histories of GDM, who are predisposed to NIDDM, have impairments both of insulin secretion and of insulin action before the development of overt hyperglycemia.