Association of fetuin-A with incident diabetes mellitus in community-living older adults: The cardiovascular health study

Joachim H. Ix, Mary L. Biggs, Kenneth J. Mukamal, Jorge Kizer, Susan J. Zieman, David S. Siscovick, Dariush Mozzaffarian, Majken K. Jensen, Lauren Nelson, Neil Ruderman, Luc Djousse

Research output: Contribution to journalArticle

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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). 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.

Original languageEnglish (US)
Pages (from-to)2316-2322
Number of pages7
JournalCirculation
Volume125
Issue number19
DOIs
StatePublished - May 15 2012
Externally publishedYes

Fingerprint

alpha-2-HS-Glycoprotein
Diabetes Mellitus
Cardiovascular Diseases
Health
Confidence Intervals
Kidney Diseases
Waist Circumference
Proportional Hazards Models
Vascular Resistance
C-Reactive Protein
Insulin Resistance
Life Style
Albumins
Body Mass Index
Demography
Hypertension
Lipids

Keywords

  • alpha-2-HS-Glycoprotein
  • cardiovascular diseases
  • diabetes mellitus
  • geriatrics
  • obesity
  • risk factors

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Ix, J. H., Biggs, M. L., Mukamal, K. J., Kizer, J., Zieman, S. J., Siscovick, D. S., ... Djousse, L. (2012). Association of fetuin-A with incident diabetes mellitus in community-living older adults: The cardiovascular health study. Circulation, 125(19), 2316-2322. https://doi.org/10.1161/CIRCULATIONAHA.111.072751

Association of fetuin-A with incident diabetes mellitus in community-living older adults : The cardiovascular health study. / Ix, Joachim H.; Biggs, Mary L.; Mukamal, Kenneth J.; Kizer, Jorge; Zieman, Susan J.; Siscovick, David S.; Mozzaffarian, Dariush; Jensen, Majken K.; Nelson, Lauren; Ruderman, Neil; Djousse, Luc.

In: Circulation, Vol. 125, No. 19, 15.05.2012, p. 2316-2322.

Research output: Contribution to journalArticle

Ix, JH, Biggs, ML, Mukamal, KJ, Kizer, J, Zieman, SJ, Siscovick, DS, Mozzaffarian, D, Jensen, MK, Nelson, L, Ruderman, N & Djousse, L 2012, 'Association of fetuin-A with incident diabetes mellitus in community-living older adults: The cardiovascular health study', Circulation, vol. 125, no. 19, pp. 2316-2322. https://doi.org/10.1161/CIRCULATIONAHA.111.072751
Ix, Joachim H. ; Biggs, Mary L. ; Mukamal, Kenneth J. ; Kizer, Jorge ; Zieman, Susan J. ; Siscovick, David S. ; Mozzaffarian, Dariush ; Jensen, Majken K. ; Nelson, Lauren ; Ruderman, Neil ; Djousse, Luc. / Association of fetuin-A with incident diabetes mellitus in community-living older adults : The cardiovascular health study. In: Circulation. 2012 ; Vol. 125, No. 19. pp. 2316-2322.
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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). 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.",
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AU - Kizer, Jorge

AU - Zieman, Susan J.

AU - Siscovick, David S.

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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.

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