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Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.

TitleAssociation of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.
Publication TypeJournal Article
Year of Publication2012
AuthorsIx, JH, Biggs, ML, Mukamal, KJ, Kizer, JR, Zieman, SJ, Siscovick, DS, Mozzaffarian, D, Jensen, MK, Nelson, L, Ruderman, N, Djoussé, L
JournalCirculation
Volume125
Issue19
Pagination2316-22
Date Published2012 May 15
ISSN1524-4539
KeywordsAfrican Continental Ancestry Group, Age Distribution, Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Body Mass Index, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Humans, Incidence, Life Style, Lipids, Male, Pilot Projects, Prevalence, Proportional Hazards Models, Residence Characteristics, Risk Factors, Sex Distribution
Abstract<p><b>BACKGROUND: </b>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).</p><p><b>METHODS AND RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1161/CIRCULATIONAHA.111.072751
Alternate JournalCirculation
PubMed ID22511752
PubMed Central IDPMC3390925
Grant ListN01 HC085086 / HC / NHLBI NIH HHS / United States
N01HC-85081 / HC / NHLBI NIH HHS / United States
N01HC-54133 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC-85079 / HC / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01HC-85085 / HC / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01HC-85084 / HC / NHLBI NIH HHS / United States
N01HC-85080 / HC / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL094555 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC-55222 / HC / NHLBI NIH HHS / United States
N01HC-85083 / HC / NHLBI NIH HHS / United States
N01HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01HC-75150 / HC / NHLBI NIH HHS / United States
N01HC-15103 / HC / NHLBI NIH HHS / United States
N01HC-85082 / HC / NHLBI NIH HHS / United States
N01HC-85086 / HC / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01- HC85239 / HC / NHLBI NIH HHS / United States