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Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes
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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 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.
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“Notably, its levels have been found increased in obesity, especially associated with NAFLD [137], and are predictive for the development of T2DM [190].”
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Metadata
- Authors
- Stefan, N., Fritsche, A., Weikert, C., Boeing, H., Joost, H.-G., Häring, H.-U., & Schulze, M. B.
- Affiliations
- University of Tübingen (DE)
- German Institute of Human Nutrition (DE)
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-10-01
- Volume
- 57
- Issue
- 10
- Pages
- 2762-2767
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2551687
- OpenAlex
- W2130626015
- Cited by
- 379
- References
- 32
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 15 · 2023: 14 · 2022: 15 · 2021: 13 · 2020: 18 · 2019: 13 · 2018: 26 · 2017: 26 · 2016: 26 · 2015: 31 · 2014: 28 · 2013: 34 · 2012: 28
- FWCI
- 17.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- fetuin-A, type 2 diabetes, diabetes risk, insulin resistance, plasma biomarkers, hyperglycemia, EPIC-Potsdam cohort
- MeSH terms
- Adult, Age Factors, Aged, Blood Proteins, Diabetes Mellitus, Type 2, Female, Germany, Humans, Life Style, Male, Middle Aged, Risk Factors, Cohort Studies, alpha-2-HS-Glycoprotein
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