Sex-Specific Association of Fetuin-A With Type 2 Diabetes in Older Community-Dwelling Adults

OBJECTIVE This study evaluated the sex-specific association of plasma fetuin-A levels with prevalent and incident type 2 diabetes in community-dwelling older adults. RESEARCH DESIGN AND METHODS Participants were 684 men and 1,058 women (median age, 71 years) whose fetuin-A levels, diabetes prevalence, and diabetes risk factors were evaluated in 1992-1996. The participants were followed for incident diabetes through 2010 (median follow-up, 9 years). RESULTS Women with impaired glucose tolerance had elevated fetuin-A levels compared with women with normal glucose tolerance (P = 0.019), but fetuin-A levels were not elevated in women with impaired fasting glucose. Fetuin-A did not vary by glucose tolerance status in men. There were significant interactions of fetuin-A by sex for prevalent (P = 0.007) and incident (P = 0.020) diabetes. For women, each SD (0.10 g/L) higher fetuin-A level was associated with a higher odds of prevalent diabetes (odds ratio [OR] 1.79, 95% CI 1.47-2.17) and greater risk of incident diabetes (hazard ratio [HR] 1.66, 95% CI 1.18-2.34), adjusting for age and estrogen therapy. These associations were not materially altered by adjustment for diabetes risk factors but were attenuated by adjusting for postchallenge glucose levels. Among men, although positive associations with prevalent (OR 1.15 [0.94-1.41]) and incident (HR 1.24 [0.93-1.65]) diabetes were suggested in age-adjusted models, risk estimates attenuated to one after multivariable adjustment. CONCLUSIONS Higher fetuin-A concentrations were independently associated with an increased risk of developing type 2 diabetes in older women but were not related to diabetes risk in older men. Fetuin-A may provide novel insights into mechanisms underlying sex differences in glucose homeostasis and diabetes risk in old age.