Insulin sensitivity and albuminuria: the RISC study

Diabetes Care. 2014 Jun;37(6):1597-603. doi: 10.2337/dc13-2573. Epub 2014 Mar 12.

Abstract

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 was 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 either is simply related to or might causally contribute to the initial pathogenesis of albuminuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / epidemiology*
  • Albuminuria / physiopathology
  • Cardiovascular Diseases / epidemiology
  • Creatinine / urine
  • Cross-Sectional Studies
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Hyperinsulinism / diagnosis
  • Incidence
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Risk Factors

Substances

  • Insulin
  • Creatinine