There is evidence from animal models that postprandial insulin hypersecretion may precede the development of obesity and insulin resistance, but it is not clear if this is the case in humans. Recently, two longitudinal studies have suggested that insulin resistance acts to limit further weight gain rather than to promote it. The relationship of markers of insulin sensitivity and secretion to changes in weight and the waist to hip ratio (WHR) was therefore examined in nondiabetic Asian Indian (n = 2,169), Creole (n = 798), and Chinese (n = 189) Mauritians over a 5-year follow-up period. Younger age and lower initial body mass index (BMI) were consistent independent predictors of increase in weight in all sex-ethnic subgroups, and older age, higher BMI, and lower WHR were associated with change in WHR. Insulin sensitivity was assessed by homeostatic model assessment (HOMAS), as well as by fasting insulin and the ratio of fasting insulin to glucose. Insulin resistance predicted weight gain in Chinese men independently of baseline age and BMI. In Asian Indian and Creole men and women, these correlations were in the opposite direction (ie, insulin sensitivity predicted weight gain) but became nonsignificant when age and BMI were controlled. There was little relationship of insulin resistance/sensitivity to the change in WHR once baseline BMI was controlled. These data provide suggestive but not convincing evidence that insulin resistance may limit weight gain, and contradictory evidence in one ethnic group that insulin resistance promotes weight gain.