Plasma fetuin-A levels and the risk of type 2 diabetes.
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.
Stefan
Norbert
N
Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
Fritsche
Andreas
A
Weikert
Cornelia
C
Boeing
Heiner
H
Joost
Hans-Georg
HG
Häring
Hans-Ulrich
HU
Schulze
Matthias B
MB
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
C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein