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 mellitus (GDM). Pregnancy is characterized by a progressive increase in nutrient-stimulated insulin responses despite an only minor deterioration in glucose tolerance, consistent with progressive insulin resistance. The hyperinsulinemic-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 compensate in GDM and glucose intolerance ensues. GDM may reflect a predisposition to type 2 diabetes or may be an extreme manifestation of metabolic alterations that normally occur in pregnancy. In normal pregnant women, basal endogenous 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 total gluconeogenesis to R(a), quantified from (2)H enrichment on carbon 5 of glucose (65-85%), does not differ in pregnant women after a 16-h fast. Endogenous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (96% suppression), but is less sensitive in GDM (80%). Commensurate with the increased rate of glucose appearance, an increased contribution of carbohydrate to oxidative metabolism has been observed in late pregnancy compared with pregravid states. The 24-h respiratory quotient is significantly higher in late pregnancy than postpartum. Recent advances in carbohydrate metabolism during pregnancy suggest that preventive measures should be aimed at improving insulin sensitivity in women predisposed to GDM. Further research is needed to elucidate the mechanisms and consequences of alterations in lipid metabolism during pregnancy.