IMPAIRED GLUCOSE-TOLERANCE IN PIMA-INDIANS

More than 50 % of Pima Indians develop NIDDM. This disorder is precede d by impaired glucose tolerance (IGT) and we tested the hypothesis tha t the elevated glucose levels in IGT must be due to reduced beta-cell function. We first determined the plasma glucose/plasma insulin and pl asma insulin/insulin resistance relationships in individuals with NGT, relationships which by definition must be normal, and determined if t hese relationships were intact in individuals with IGT. We also compar ed Pimas and Caucasians with NGT or IGT. Subjects were assessed with a n OGTT, an IVGTT, underwater weighing (for body composition), and a eu glycaemic clamp. The results showed that insulin concentrations in Pim as with IGT were not lower than the levels predicted by the relationsh ips found in subjects with NGT. Compared to Caucasians, Pima Indians h ad elevated insulin concentrations at the same degree of insulin resis tance. These studies indicate that insulin resistance, and not beta-ce ll failure, is the principal lesion determining IGT in Pimas. NIDDM oc curs when beta-cell failure develops in the presence of insulin resist ance. In some individuals of other races, beta-cell function may be le ss able to withstand insulin resistance, and presumably in these indiv iduals beta-cell failure assumes a greater importance in the evolution to NIDDM.