The effects of single and sequential insulin infusions on glucose disposal in older men

The hyperinsulinemic euglycemic glucose clamp is widely used to quantitate in vivo insulin action. Modification of this technique by sequentially infusing multiple doses of insulin allows determination of insulin sensitivity and maximal responsiveness; however, the validity of this approach has not been determined in older individuals. In this study, glucose disposal rates during a sequential three-dose clamp at insulin infusion rates of 20, 100, and 500 mU/m2.min were compared to those obtained during a single-dose 100 mU/m2.min clamp in eight healthy older men. There were no differences in plasma insulin levels (256 +/- 46 vs. 261 +/- 32 microU/ml) or glucose disposal rates (11.0 +/- 3.6 vs. 10.8 +/- 3.0 mg/kgfat-free mass.min) during the 100 mU/m2.min infusion of the three-dose clamp and the one-dose clamp. In four subjects with impaired glucose tolerance, the EC50 (insulin concentration producing a half-maximal response) was higher and Mmax (maximal glucose disposal) lower than in subjects with normal glucose tolerance, suggesting impairments in both insulin sensitivity and responsiveness in older subjects with impaired glucose tolerance. Future studies using this modification of the hyperinsulinemic euglycemic glucose clamp to determine insulin sensitivity and responsiveness may lead to an improved understanding of the insulin resistance of aging and the pathogenesis of diseases such as diabetes and hypertension.