OBJECTIVE: Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes meffitas (GDM). We examined the association between plasma leptin concentration and GDM risk. METHODS: Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95%confidence intervals. RESULTS: GDM developed in 5.7%of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend < .001). After adjusting for maternal prepregnancy adiposity and other confounders, women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM (95%confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10 ng/mL increase in the leptin concentration was associated with a 20%increase in GDM risk (relative risk 1.2; 95%confidence interval 1.0, 1.3). CONCLUSIONS: Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. OBJECTIVE: Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that METHODS: Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations may be increased in pregnancies complicated by gestational diabetes meffitas (GDM). We collected generalized linear models to estimate relative risks and 95% confidence intervals. RESULTS: GDM developed in 5.7% of the cohorts (47 of 823). Elevated leptin concentrations were associated with GDM risk (P for trend <.001). After adjusting for maternal prepregnancy adiposity and other co nfounders, women with leptin concentrations of 31.0 ng / mL or higher experienced a 4.7-fold increased risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng / mL or lower. linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10 ng / mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). CONCLUSIONS : Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy.