Insulin secretion and in vivo insulin action were quantified in nonobese and moderately obese subjects (approximately 35% above desirable body weight) with normal glucose tolerance. Insulin secretion was estimated by determining plasma insulin responses to a 75-g oral challenge, and in vivo insulin-stimulated glucose uptake by the euglycemic clamp technique.

Plasma glucose levels of the two groups were identical during the glucose tolerance test, butthe plasma insulin response was significantly greater (P < 0.01) in the bese subjects. However, insulin-stimulated glucose utilization by the two groups was equal during the euglycemic clamp studies. These results were supported by the fact that degree of obesity correlated significantly with insulin response (r = 0.61, P < 0.005), but not with insulin-stimulated glucose utilization (r = −0.25, P > 0.2). Thus, indirect evidence that moderately obese subjects were more insulin-resistant based on measurement of plasma insulin responsewas not supported by direct quantification of insulin action. One explanation for these findings is that the height of the plasma insulin response bears no relationship to loss of in vivo insulin action, but that seems unlikely in view of the fact that there was a significant correlation (r = −0.52, P < 0.01) between these two variables in the group as a whole. Therefore, it appears that the hyperinsulinemia seen in obese individuals may not be a simple function of insulin resistance, and that the ability of insulin to stimulate glucose utilization is not significantly impaired in moderately obese subjects with normal glucose tolerance. Alternatively, the degree of impairment in insulin action seen in these individuals is insufficient to be detected by the euglycemic clamp technique.

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