OBJECTIVE: To determine if levels of the adipocyte-derived hormone, leptin, predict the development of type 2 diabetes. METHODS: Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987, 1992 and 1998. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. A cohort of 2330 participants who were free of diabetes, aged 25-79 years in 1987, and who were followed-up in 1992 and 1998 was studied. Serum leptin was measured in baseline samples. Glucose tolerance was classified according to WHO (World Health Organization) 1999 criteria. RESULTS: In total, 456 subjects developed diabetes over 11 years with similar incidences in all ethnic groups (P=0.2). Baseline leptin correlated positively with anthropometric measurements, fasting and postload insulin and homeostasis model assessment indices (all P<0.001), and inversely with subsequent weight increase. Participants with incident diabetes had higher serum levels of leptin at baseline than those remaining nondiabetic (P<0.001). After adjustment for confounders, high leptin levels and high leptin/body mass index ratio were independently associated with incident diabetes over 11 years in men (odds ratio for top versus bottom quartile of leptin 2.18; 95% CI: 1.09-4.35), but not in women. CONCLUSION: We conclude that high leptin levels are associated with the future development of diabetes, and the association is independent of other factors in men, but not in women.