Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus

This article reviews maternal metabolic strategies for accommodating fetal nutrient requirements in normal pregnancy and in gestational diabetes melli tus (GDM). Pregnancy is characterized by a progressive increase in nutrient -stimulated insulin responses despite an only minor deterioration in glucos e tolerance, consistent with progressive insulin resistance. The hyperinsul inemic-euglycemic glucose clamp technique and intravenous-glucose-tolerance test have indicated that insulin action in late normal pregnancy is 50-70% lower than in nonpregnant women. Metabolic adaptations do not fully compen sate in GDM and glucose intolerance ensues. GDM may reflect a predispositio n to type 2 diabetes or may be an extreme manifestation of metabolic altera tions that normally occur in pregnancy. In normal pregnant women, basal end ogenous hepatic glucose production (R-a) was shown to increase by 16-30% to meet the increasing needs of the placenta and fetus. Total gluconeogenesis is increased in late gestation, although the fractional contribution of to tal gluconeogenesis to R-a, quantified from H-2 enrichment on carbon 5 of g lucose (65-85%), does not differ in pregnant women after a 16-h fast. Endog enous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (96% suppression), but is less s ensitive in GDM (80%). Commensurate with the increased rate of glucose appe arance, an increased contribution of carbohydrate to oxidative metabolism h as been observed in late pregnancy compared with pregravid states. The 24-h respiratory quotient is significantly higher in late pregnancy than postpa rtum. Recent advances in carbohydrate metabolism during pregnancy suggest t hat preventive measures should be aimed at improving insulin sensitivity in women predisposed to GDM. Further research is needed to elucidate the mech anisms and consequences of alterations in lipid metabolism during pregnancy .