Mechanisms of insulin resistance in aging

yr, respectively) to assess the mechanisms responsible for the abnormal carbohydrate tolerance associated with aging. Serum glucose and insulin levels were sig-nificantly elevated in the elderly subjects compared with the nonelderly subjects during a 75-g oral glucose tolerance test, suggesting an insulin resistant state. Peripheral insulin sensitivity was assessed in both groups using the euglycemic glucose clamp technique during an insulin infusion rate of 40 mU/M2 per min. Similar steady-state serum insulin levels led to a pe-ripheral glucose disposal rate of 151±17 mg/M2 per min in the elderly compared with a value of 247±12-mg/M2 per min in the nonelderly, thus documenting the presence of insulin resistance in the elderly sub-jects. Insulin binding to isolated adipocytes and monocytes was similar in the elderly and nonelderly groups (2.34±0.33 vs. 2.62±0.24 % and 5.04±1.10 vs. 5.12±1.07%), respectively. Thus, insulin resistance in the presence of normal insulin binding suggests the presence of a postreceptor defect in insulin action. This was confirmed by performing additional euglycemic clamp studies using infusion rates of 15 and 1,200 mU/ m2 per min to assess the contours of the dose-response relationship. These studies revealed a 39 and 25 % de-crease in the glucose disposal rate in the elderly sub-jects, respectively. The results confirm the presence of a postreceptor defect as well as a rightward shift in the dose-response curve. Insulin's ability to suppress hepatic glucose output was less in the elderly subjects Dr. Kolterman was the recipient of a Clinical Investigato