With advancing age, glucose-induced insulin release is decreased in vitro, yet circulating insulin levels after glucose challenge are not decreased in the elderly. Age-related changes in insulin clearance may contribute to this discrepancy. We employed the 2-h euglycemic clamp technique to examine insulin clearance (C1) during steady-state insulin infusions (N = 53) at rates of 20, 80, and 200 mU/m2/min in healthy young (N = 16, age range 22–37 yr, relative weight 1.07 ± 0.03) and old (N = 10, age range 63–77 yr, relative weight 1.14 ± 0.03) men. Steady-state insulin levels were statistically significantly higher (P < 0.01) in the elderly at each infusion rate. C1 was 40% lower (p < 0.01) in the infusion rate. There was no effect of increasing relative weight on C1 within age groups. Within each age group, C1 was similar in insulin infusion rates of 20 and 80 mU/m2/min (young P < 0.05, old P < 0.001), implying a saturable system for insulin clearance. Alterations in C1 contribute to changes in insulin levels with age and may reconcile the discrepancy between in vivo and in vitro studies of glucose-induced insulin release. These results indicate the value of evaluating C1 as one determinant of circulating insulin level in states of abnormal insulin physiology.

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