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Joachim H. Ix, MD, MAS; Christina L. Wassel, MS; Alka M. Kanaya, MD; Eric Vittinghoff, PhD; Karen C. Johnson, MD, MPH; Annemarie Koster, PhD; Jane A. Cauley, DrPh; Tamara B. Harris, MD; Steven R. Cummings, MD; Michael G. Shlipak, MD, MPH; for the Health ABC Study

JAMA. 2008;300(2):182-188.

Context  Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action in vitro. In prior cross-sectional studies in humans, higher fetuin-A levels were associated with insulin resistance. However, the longitudinal association of fetuin-A with incident type 2 diabetes mellitus is unknown.

Objective  To determine whether fetuin-A levels are associated with incident diabetes in older persons.

Design, Setting, and Participants  Observational study among 3075 well-functioning persons aged 70 to 79 years. In this case-cohort study, we retrospectively measured fetuin-A levels in baseline serum among 406 randomly selected participants without prevalent diabetes, and all participants who developed incident diabetes mellitus during a 6-year follow-up (to August 31, 2005).

Main Outcome Measure  Incident diabetes mellitus.

Results  Incident diabetes developed in 135 participants (10.1 cases/1000 person-years). Participants with fetuin-A levels within the highest tertile (> 0.97 g/L) had an increased risk of incident diabetes (13.3 cases/1000 person-years) compared with participants in the lowest tertile ( 0.76 g/L) (6.5 cases/1000 person-years) in models adjusted for age, sex, race, waist circumference, body weight, physical activity, blood pressure level, fasting glucose level, high-density lipoprotein cholesterol concentration, triglyceride concentration, and C-reactive protein level (adjusted hazard ratio, 2.41; 95% confidence interval, 1.28-4.53; P = .007). The association was not affected by adipocytokine levels but was moderately attenuated by adjustment for visceral adiposity (adjusted hazard ratio of highest vs lowest tertile 1.72; 95% confidence interval, 0.98-3.05; P = .06).

Conclusion  Among well-functioning older persons, serum fetuin-A is associated with incident diabetes, independent of other markers of insulin resistance.

Author Affiliations: Division of Nephrology and Hypertension, Department of Medicine, and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, San Diego, and San Diego Veterans Affairs Healthcare System, San Diego, California (Dr Ix); Department of Epidemiology, University of Minnesota, Minneapolis (Ms Wassel); Department of Epidemiology and Biostatistics (Ms Wassel and Drs Vittinghoff and Shlipak) and Department of Medicine (Drs Kanaya, Cummings, and Shlipak), University of California, San Francisco; Department of Medicine, University of Tennessee Health Science Center, Memphis (Dr Johnson); Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland (Drs Koster and Harris); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Cauley); Department of Medicine, California Pacific Medical Center and San Francisco Coordinating Center, San Francisco (Dr Cummings); and San Francisco Veterans Affairs Medical Center, San Francisco (Dr Shlipak).

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