Insulin Sensitivity and Albuminuria: The RISC Study

OBJECTIVE Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN AND METHODS We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity was assessed by hyperinsulinemic–euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test–based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS Microalbuminuria (UACR ≥30 mg/g) was present in fewer than 2% at either study visit. After multivariate adjustments, there was no cross-sectional association between UACR and any measure of insulin sensitivity. Neither OGIS nor HOMA-IR were significantly associated with follow-up UACR, but in a multivariate regression analysis, baseline M/I emerged as an independent predictor of UACR at follow-up (β-coefficient −0.14; P = 0.001). CONCLUSIONS In healthy middle-aged adults, reduced insulin sensitivity, assessed by hyperinsulinemic–euglycemic clamp, is continuously associated with a greater risk of increasing albuminuria. This finding suggests that reduced insulin sensitivity is either simply related to or might causally contribute to the initial pathogenesis of albuminuria.