Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes

  1. Norbert Stefan1,
  2. Andreas Fritsche1,
  3. Cornelia Weikert2,
  4. Heiner Boeing2,
  5. Hans-Georg Joost3,
  6. Hans-Ulrich Häring1 and
  7. Matthias B. Schulze24
  1. 1Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany
  2. 2Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  3. 3Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  4. 4Public Health Nutrition Unit, Technische Universität München, Freising, Germany
  1. Corresponding author: Matthias B. Schulze, matthias.schulze{at}


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.

RESEARCH DESIGN AND 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 μg/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 μg/ml 1.03 [1.01–1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, γ-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 μg/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.


  • Published ahead of print at on 15 July 2008.

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    • Accepted June 30, 2008.
    • Received April 22, 2008.
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  1. Diabetes vol. 57 no. 10 2762-2767
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