THE EFFECT OF AGE ON INSULIN-RESPONSE AND GLUCOSE-UTILIZATION DURING 4 HYPERGLYCEMIC PLATEAUS

In order to evaluate the potential role of insulin insensitivity as a cause of the glucose (G) intolerance of aging, we performed 230 hyperg lycemic clamps, 85 on young (Y, 24 to 39 years), 47 on middle age (M, 40 to 59 years), and 98 on old (0, 60 to 90 years) carefully screened subjects of the Baltimore Longitudinal Study of Aging. The 2-h plasma G levels on an oral glucose tolerance test (OGTT) were < 7.8 mmol/l in Y and M and < 10 mmol/l in old; the latter group was further dichotom ized at 7.8 mmol/l into a ''normal'' group, ON, and an impaired group, OI. Four hyperglycemic plateaus were created: 3.0, 5.4, 7.9, and 12.8 mmol/l above basal. Three measures of glucose tolerance-1) G at 2 h a fter glucose ingestion, 2) glucose utilization, M, at each hyperglycem ic plateau, and 3) glucose decay constant, K, obtained at the conclusi on of each clamp-showed the best performance in the young group (Y > M = ON > OI). Despite these differences in glucose tolerance, plasma in sulin responses (I) during the clamp were not significantly different except that ON < Y at the basal + 12.8 plateau (300 t 42 vs. 456 +/- 4 8 pmol/l, p < 0.01). Insulin-dependent glucose uptake, a measure of ti ssue sensitivity to insulin, was decreased in the old-impaired group a t every plateau except the highest. We conclude that healthy, active o lder subjects showed moderate intolerance to oral and IV glucose and t hat the mechanism of this physiological aging process is most likely d ecreased insulin sensitivity.