title: Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.
abstract: 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).
  
  
  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.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego VA Healthcare System, San Diego, CA 92161, USA. joeix@ucsd.edu
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Zieman
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozzaffarian
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Lauren
authors.initials: L
authors.lastname: Nelson
authors.forename: Neil
authors.initials: N
authors.lastname: Ruderman
authors.forename: Luc
authors.initials: L
authors.lastname: Djousse
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000706:statistics & numerical data; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D008019:Life Style; D008055:Lipids / Q000097:blood; D008297:Male; D010865:Pilot Projects; D015995:Prevalence; D016016:Proportional Hazards Models; D012111:Residence Characteristics; D012307:Risk Factors; D017678:Sex Distribution; D044465:White People / Q000706:statistics & numerical data; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: D008055:Lipids; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein