Longitudinal changes in glucose metabolism during pregnancy in obese womenwith normal glucose tolerance and gestational diabetes mellitus

OBJECTIVE: This study prospectively evaluated the longitudinal changes in i nsulin sensitivity, insulin response, and endogenous (primarily hepatic) gl ucose production and suppression during insulin infusion in women with norm al glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom gestational dia betes mellitus developed were evaluated with an oral glucose tolerance test , an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic cl amp with infusion of [6,6 H-2(2)]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area u nder the curve during the intravenous glucose tolerance test. Basal endogen ous glucose production was estimated from isotope tracer dilution during st eady state with [6,6 H-2(2)]glucose and suppression during insulin infusion . Insulin sensitivity to glucose was defined as the glucose infusion rate r equired to maintain euglycemia during steady-state insulin infusion. Body c omposition was estimated with hydrodensitometry. Data were analyzed with 2- way analysis of variance with repeated measures for 2 groups. RESULTS: There were increases in first-phase (P = .006) and second-phase (P = .0001) insulin responses in both groups with advancing gestation, but th e increase in second-phase response was significantly greater(P = .02) in t he gestational diabetes mellitus group than in the control group. Basal glu cose production increased significantly (P = .0001) with advancing gestatio n, and there was resistance to suppression during insulin infusion in both groups (P = .0001). There was less suppression of endogenous glucose produc tion however, in the gestational diabetes mellitus group than in the contro l group (P = .01). Insulin sensitivity decreased with advancing gestation i n both groups (P = .0001), and there was lower insulin sensitivity in the g estational diabetes mellitus group than in the control group (P = .04). Sig nificant decreases in insulin sensitivity with time (P = .0001) and between groups (P = .03) remained when the data were adjusted for differences in i nsulin concentration or residual hepatic glucose production. CONCLUSION: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensit ivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These me tabolic abnormalities in glucose metabolism are the hallmarks of type 2 dia betes, for which these women are at increased risk in later life.