Insulin Sensitivity and Albuminuria: The RISC Study

Abstract

OBJECTIVEAccumulating 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 METHODSWe investigated 1,415 healthy, nondiabetic participants (mean age 43.9 6 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 hyperinsulinemiceuglycemic 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. RESULTSMicroalbuminuria (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 (b-coefficient 20.14; P = 0.001). CONCLUSIONSIn 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.Higher levels of albuminuria are associated with an increased risk of mortality and cardiovascular events in patients with diabetes mellitus or arterial hypertension and the general population (1-3). Insights into the pathophysiology of albuminuria are of high clinical relevance since therapeutic interventions to reduce albuminuria are often accompanied by improvements in cardiovascular outcomes (3). Microalbuminuria is also regarded as a marker of a certain form of endothelial dysfunction, but there exists still no clear picture on the direction of the cause and effect relationship (4-6). Alternatively, microalbuminuria and vascular diseases/endothelial dysfunction may also be caused by a common pathophysiologic process (7).

Prediabetes and Risk of Glomerular Hyperfiltration and Albuminuria in the General Nondiabetic Population: A Prospective Cohort Study

“…We also adjusted for fasting insulin levels because reduced insulin sensitivity has been associated with greater risk of albuminuria. 37 Our results are noteworthy because ACR > 10 mg/g has been found to predict CVD, CKD and death in general-population cohorts. 23,24 Importantly, potential interventions like diet and physical activity promotion programs in prediabetes have been shown to reduces glucose levels.…”

Response to Comment on Pilz et al. Insulin Sensitivity and Albuminuria: The RISC Study. Diabetes Care 2014;37:1597–1603

“…We thank Bastard and Fellahi (1) for their comments on our RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study results (2). We showed in healthy individuals that reduced insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp and expressed as the M/I value, is continuously associated with a greater risk of increasing albuminuria (2).…”

“…We showed in healthy individuals that reduced insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp and expressed as the M/I value, is continuously associated with a greater risk of increasing albuminuria (2). Oral glucose tolerance test2based insulin sensitivity and homeostasis model of assessment of insulin resistance were not significantly associated with urinary albumin-to-creatinine ratio (UACR) (2). In this context, Bastard and Fellahi raised the question as to whether other surrogates of insulin sensitivity, such as the triglycerides and glucose index, McAuley index, or the revised quantitative insulin sensitivity check index, are significantly associated with albuminuria (1,3).…”

“…We showed in healthy individuals that reduced insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp and expressed as the M/I value, is continuously associated with a greater risk of increasing albuminuria (2). Oral glucose tolerance test2based insulin sensitivity and homeostasis model of assessment of insulin resistance were not significantly associated with urinary albumin-to-creatinine ratio (UACR) (2).…”

“…In this context, Bastard and Fellahi raised the question as to whether other surrogates of insulin sensitivity, such as the triglycerides and glucose index, McAuley index, or the revised quantitative insulin sensitivity check index, are significantly associated with albuminuria (1,3). We therefore performed multiple linear regression analyses using the same covariates as in our original RISC study article to assess whether these indices are associated with UACR (2). As a result, we found that none of these surrogates of insulin sensitivity were significantly associated with UACR at baseline or at follow-up (P .…”