%0 Journal Article %J Circulation %D 2012 %T Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study. %A Ix, Joachim H %A Biggs, Mary L %A Mukamal, Kenneth J %A Kizer, Jorge R %A Zieman, Susan J %A Siscovick, David S %A Mozzaffarian, Dariush %A Jensen, Majken K %A Nelson, Lauren %A Ruderman, Neil %A Djoussé, Luc %K African Continental Ancestry Group %K Age Distribution %K Aged %K Aged, 80 and over %K alpha-2-HS-Glycoprotein %K Body Mass Index %K C-Reactive Protein %K Cardiovascular Diseases %K Diabetes Mellitus, Type 2 %K European Continental Ancestry Group %K Female %K Humans %K Incidence %K Life Style %K Lipids %K Male %K Pilot Projects %K Prevalence %K Proportional Hazards Models %K Residence Characteristics %K Risk Factors %K Sex Distribution %X

BACKGROUND: The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD).

METHODS AND RESULTS: Among 3710 community-living individuals ≥ 65 years of age without diabetes mellitus at baseline, fetuin-A was measured in serum collected in 1992 to 1993. Participants were followed up for 10.6 years (median) for incident diabetes mellitus. Cox regression models evaluated the association of fetuin-A with incident diabetes mellitus. Interaction terms evaluated heterogeneity by age, sex, race, and CVD. Mean age was 75 years; 60 were female; 15 were black; and 16 had CVD. Mean fetuin-A concentrations were 0.47 ± 0.10 g/L. During follow-up, 305 incident diabetes cases occurred. Each 0.10-g/L (SD)-greater fetuin-A was associated with 19 higher risk of diabetes mellitus (hazard ratio, 1.19; 95 confidence interval, 1.06-1.33) after adjustment for demographics, lifestyle factors, albumin, kidney function, and CVD. Further adjustment for potential mediators (body mass index, waist circumference, hypertension, lipids, and C-reactive protein) moderately attenuated the association (hazard ratio, 1.13; 95 confidence interval, 1.00-1.28). Results were similar by sex, race, and CVD status but were stronger in persons <75 years old (P for interaction=0.01).

CONCLUSIONS: Higher fetuin-A is associated with incident diabetes mellitus in older persons regardless of sex, race, or prevalent CVD status. The association may be attenuated in those ≥ 75 years of age.

%B Circulation %V 125 %P 2316-22 %8 2012 May 15 %G eng %N 19 %1 http://www.ncbi.nlm.nih.gov/pubmed/22511752?dopt=Abstract %R 10.1161/CIRCULATIONAHA.111.072751