title: Plasma fetuin-A levels and the risk of type 2 diabetes.
abstract: OBJECTIVE
  The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study.
  
  
  METHODS
  A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions.
  
  
  RESULTS
  Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32-2.31]; RR for 10 mug/ml 1.04 [1.03-1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.
  
  
  CONCLUSIONS
  Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Schulze
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein