Influence of Age on Clearance of Insulin in Man

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.