Fetuin-A and incident diabetes mellitus in older persons

JAMA. 2008 Jul 9;300(2):182-8. doi: 10.1001/jama.300.2.182.


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 (< or = 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat
  • Adiposity
  • Age Factors
  • Aged
  • Biomarkers / blood
  • Blood Proteins / metabolism*
  • Body Composition
  • Case-Control Studies
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Follow-Up Studies
  • Health Status
  • Humans
  • Insulin Resistance
  • Male
  • Retrospective Studies
  • Risk Factors
  • alpha-2-HS-Glycoprotein


  • AHSG protein, human
  • Biomarkers
  • Blood Proteins
  • alpha-2-HS-Glycoprotein