Glucose intolerance and aging. Evidence for tissue insensitivity to insulin

The relative contributions of impaired insulin secretion and impaired tissue sensitivity to insulin to the glucose intolerance of aging were examined in 84 healthy volunteers, ranging in age from 21 to 84 yr, employing the hyperglycemic and euglycemic insulin clamp techniques, respectively. Hyperglycemic clamp: the blood glucose concentration was acutely raised and was maintained at 125 mg/dl above basal levels for 2 h. Since the glucose concentration was held constant, the glucose infusion rate was an index of glucose metabolism (M). In young subjects, M averaged 9.48 ± 0.40 mg/kg min compared with 6.48 ± 0.28 in old subjects (P<0.001). When all subjects were considered together, a progressive age-related decline in M was observed (r=-0.665, P<0.001). The plasma insulin response (I) was biphasic, with an early burst within the first 6 min, followed by a phase of gradually increasing insulin concentration. No difference in either the early or late phases of insulin secretion was observed between young and old subjects. Consequently, the M/I (x100) ratio, an index of tissue sensitivity to endogenous insulin, decreased from 14.90 ± 1.01 to 10.98 ± 0.81 mg/kg min per μU/ml (P<0.005). Euglycemic insulin clamp: the plasma insulin concentration was acutely raised and was maintained at about 100 μU/ml above basal levels by a primed continuous infusion of insulin. The blood glucose concentration was held constant at the basal level by a variable glucose infusion. M/I (x100), again, was a measure of tissue sensitivity to insulin (exogenous) and was decreased in old (4.95 ± 0.31 mg/kg x min per μU/ml) versus young (6.95 ± 0.45) subjects (P<0.001). Hepatic glucose production was measured with tritiated glucose during euglycemic clamp study; it declined similarly in young (to 0.13 ± 0.05 mg/kg x min) and old (to 0.09 ± 0.03 mg x min) subjects.