title: Insulin sensitivity and albuminuria: the RISC study.
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.
  
  
  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.
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the NetherlandsDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria stefan.pilz@chello.at.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Rutters
authors.affiliation: Department of General Practice, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: John J
authors.initials: JJ
authors.lastname: Nolan
authors.affiliation: INSERM, CESP Centre for Research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse and Determinants of Early Nutrition, Villejuif, FranceUniversity of Paris-Sud 11, Villejuif, France.
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000453:epidemiology* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000175:diagnosis; D015994:Incidence; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D007328:Insulin; D003404:Creatinine