Increased Insulin Resistance in Obese, Glucose-Intolerant Southwestern American Indians: Evidence for a Defect Not Explained by Obesity*

Abstract

Increased in vivo resistance to insulin-mediated glucose disposal has been observed in obese subjects with normal glucose tolerance and in nonobese subjects with glucose intolerance. To determine whether the insulin resistance of glucoseintolerant obese subjects can be accounted for by obesity alone, insulin-mediated glucose disposal was measured in 14 glucoseintolerant and 21 nondiabetic Southwestern American Indians with similar degrees of obesity. A mixture of insulin, glucose, and somatostatin was infused which delivered the same quantity of glucose and achieved similar plasma insulin concentrations in all subjects. Despite similar steady state plasma insulin levels, the mean steady state plasma glucose concentration was higher in the glucose-intolerant subjects than in weight-matched subjects with normal glucose tolerance (226 ± 10 vs. 136 ± 13 mg/dl; P < 0.0001). This increased resistance to insulin action was found in the presence of similar insulin binding to mononuclear cells (measured in 8 glucose-intolerant subjects and 9 subjects with normal glucose tolerance). In obese Southwestern American Indians with glucose intolerance, abnormalities beyond the site of insulin binding to its receptor may explain the observed increase in in vivo insulin resistance.