Fetuin-A and incident diabetes mellitus in older persons

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.