OBJECTIVE To evaluate whether risk factors and changes in insulin concentrations differ in subjects who develop impaired glucose tolerance with or without weight gain. Hyperinsulinemia is a risk factor for impaired glucose tolerance, and insulin concentrations increase further with the development of impaired glucose tolerance. Its development, however, often is accompanied by weight gain, which, by itself, is associated with high insulin concentrations.

RESEARCH DESIGN AND METHODS Participants for this study were adult Pima Indians involved in an ongoing epidemiological study. Initially, all had normal glucose tolerance. During follow-up, 80 of 387 who did not gain weight developed impaired glucose tolerance, as did 295 of 1026 who gained weight. Risk factors for impaired glucose tolerance and the relationships between changes in weight and glucose and changes in insulin were evaluated by multivariate analyses.

RESULTS High baseline fasting insulin predicted impaired glucose tolerance regardless of weight after adjustment for age, sex, body mass index, and glucose. The development of impaired glucose tolerance was accompanied by a further increase in fasting and 2-h insulin, whether or not subjects gained weight. In both weight-change groups, impaired glucose tolerance was associated with more centralized fat distribution.

CONCLUSIONS Fasting hyperinsulinemia, a reflection of insulin resistance, is associated with the risk of developing impaired glucose tolerance whether or not weight is gained. Impaired glucose tolerance occurs when insulin resistance increases further. Weight gain is the most common precipitating factor. Aging and physical inactivity are other possible precipitating factors.