Our primary objective was to evaluate the changes in energy expenditure and body composition in women with normal glucose tolerance (NGT) and gestational diabetes (GDM). A secondary objective was to examine the relationship between maternal leptin and nutrient metabolism. Fifteen obese women 8 with NGT and 7 with GDM were evaluated prior to conception (P) at 12-14 weeks (E) and 34-36 weeks (L). Energy expenditure and glucose and fat metabolism were measured using indirect calorimetry. Basal hepatic glucose production was measured using [6,6 ²H₂] glucose and insulin sensitivity by the euglycemic clamp. There was a significant increase (6.6 kg, p=0.0001) in fat mass (FM) from time P to L. There was a 30% (p=0.0001) increase in basal VO₂ (ml/min). There were no significant changes in carbohydrate oxidation during fasting or storage from P to L. There was, however, a significant (p=0.0001) 150% increase in basal fat oxidation (mg/min) from P to L. Under hyperinsulinemic conditions there were similar 25% increases in VO₂ (p=0.0001) from P to L in both groups. Because of the significant increases in insulin resistance from P to L, there was a significant (p=0.0001) decrease in carbohydrate oxidation and storage. There was a net change from lipogenesis to lipolysis, i.e. fat oxidation (30- 40 mg/min, p=0.0001) from P to L. Serum leptin concentrations had a significant positive correlation with fat oxidation at time E (r=0.76, p=0.005) and L (r=0.72, p=0.009). Pregnancy in obese women is associated with significant increases in fat mass, basal metabolic rate and an increased reliance on lipids both in the basal state and during the clamp. These modifications are similar in women with NGT and GDM. The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The increase in fat oxidation may be related to increased maternal serum leptin.