Increased In Vivo Insulin Resistance in Nondiabetic Pima Indians Compared with Caucasians

Abstract

Pima Indian adults have the highest reported prevalence of non-insulin-dependent (type II) diabetes mellitus and an extraordinary prevalence of obesity. Before development of fasting hyperglycemia, insulin concentrations in the Pimas are elevated both during fasting and after a glucose challenge, suggesting resistance to insulin action. To determine if Pima hyperinsulinemia is associated with resistance to insulin- mediated glucose disposal and if there are racial differences in insulin resistance not attributable to obesity, insulin resistance and the plasma insulin response to oral glucose were measured in Pima Indians and Caucasians with normal glucose tolerance and varying degrees of obesity. Fasting insulin concentrations, adjusted for obesity, age, and sex, were similar in both groups, and similar relationships were found in the Pima and Caucasian subjects between obesity, fasting insulin levels, and the insulin response to oral glucose. Resistance to exogenous insulin was measured by the steady-state plasma glucose (SSPG) technique, where a mixture of insulin, glucose, and somatostatin is infused, and the plasma glucose concentration attained is taken as a measure of insulin resistance. SSPG concentrations in both Pimas and Caucasians correlated significantly with obesity and with the fasting insulin concentrations. SSPG levels were significantly higher in the Pimas (P < 0.01) and remained so even after adjustment for obesity, age, and sex (35 ± 1 2 mg/dl higher in Pimas than in Caucasians, P < 0.01), indicating that hyperinsulinemia in the Pimas reflects a resistance to insulin action and that a greater degree of insulin resistance occurs in nondiabetic Pimas than in similarly obese Caucasians. This resistance to insulin-mediated glucose metabolism may contribute to the high incidence of diabetes in the Pima Indian population.