Impaired insulin-stimulated nonoxidative glucose metabolism in glucose-tolerant women with previous gestational diabetes

OBJECTIVE: Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes, STUDY DESIGN: Twelve women with previous gestational diabetes and 11 controls were examined by oral and intravenous glucose tolerance tests and a hyperinsulinemic euglycemic clamp including indirect calorimetry. All women were lean and had normal oral glucose tolerance test results. Activities of glycogen synthase, phosphofructokinase, and hexokinase were measured in vastus lateralis muscle biopsy specimens obtained in the basal state and after insulin stimulation. RESULTS: Women with previous gestational diabetes had a decreased glucose disposal rate (rho < 0.01) because of a reduced insulin-stimulated nonoxidative glucose metabolism (6.63 +/- 0.47 vs 9.04 +/- 0.57 mg/kg fat-free mass per minute, rho < 0.01). The muscle activities of glycogen synthase, phosphofructokinase, and hexokinase were similar in the two groups. The first-phase insulin response to the intravenous glucose tolerance test was, in absolute terms, comparable in the two groups. However, when the decreased insulin sensitivity was taken into account, women with previous gestational diabetes had a relative insulin secretion deficiency. CONCLUSION: Women with previous gestational diabetes have a decreased insulin sensitivity and a relative impairment of insulin secretion.