Fasting insulin modifies the relation between age and renal function

Abstract

The worldwide increase in end-stage renal disease has been alleged to be associated with insulin resistance-related conditions. Insulin resistance and the concomitant compensatory hyperinsulinaemia may accelerate age-related decline in renal function through inducing glomerular hyperfiltration, even in non-diabetic subjects. This population-based study is the first to investigate whether fasting insulin concentrations modify the relationship between age and renal function in a general non-diabetic population. Fasting insulin was measured in 3432 subjects, representing the general population. Cross-sectional analyses of the association between age, renal function and its modification by insulin were performed by means of linear regression. Renal function was assessed as 24-h creatinine clearance (CrCl) and 24-h urinary albumine excretion (UAE). Age was 48 +/- 12 (range: 28-75) years, 44% were male, CrCl was 100 +/- 26 ml/min and UAE was 7.0 (5.4-10.7)] mg/24 h. The results confirmed a parabolic relation between age and renal function. Fasting insulin modified these parabolic relationships of age with CrCl and UAE (P < 0.001 for both interaction terms), in such a way that hyperinsulinaemia is associated with a stronger inverse parabolic relation between age and CrCl, and stronger positive parabolic relation between age and UAE at an older age than lower insulin concentrations. Our results are consistent with the hypothesis that insulin accelerates the age-related decline of renal function in the general non-diabetic population. This indicates that insulin resistance, and the concomitant compensatory hyperinsulinaemia could contribute to the increased incidence in end-stage renal disease.