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.
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 diabetes cases 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 (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, HbA1c, γ-glutamyltransferase, or hs-CRP 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.
Footnotes
- Received April 22, 2008.
- Accepted June 30, 2008.
- Copyright © American Diabetes Association