TY - JOUR
T1 - Association of fetuin-A with incident diabetes mellitus in community-living older adults
T2 - The cardiovascular health study
AU - Ix, Joachim H.
AU - Biggs, Mary L.
AU - Mukamal, Kenneth J.
AU - Kizer, Jorge R.
AU - Zieman, Susan J.
AU - Siscovick, David S.
AU - Mozzaffarian, Dariush
AU - Jensen, Majken K.
AU - Nelson, Lauren
AU - Ruderman, Neil
AU - Djousse, Luc
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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.
AB - 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.
KW - alpha-2-HS-Glycoprotein
KW - cardiovascular diseases
KW - diabetes mellitus
KW - geriatrics
KW - obesity
KW - risk factors
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U2 - 10.1161/CIRCULATIONAHA.111.072751
DO - 10.1161/CIRCULATIONAHA.111.072751
M3 - Article
C2 - 22511752
AN - SCOPUS:84861229192
SN - 0009-7322
VL - 125
SP - 2316
EP - 2322
JO - Circulation
JF - Circulation
IS - 19
ER -