Abstract MP45: Liver Fat Content Does Not Account for the Strong Association of Fetuin-A with Diabetes Risk in Women: The Multi-Ethnic Study of Atherosclerosis
Introduction: Fetuin-A, a hepatic secretory protein, has been associated with risk of diabetes. However, liver fat content may be an important confounder or effect modifier not fully accounted for in previous studies. Further, it remains unclear whether associations differ between women and men.
Aim: In an ethnically diverse cohort of women and men, we assessed the association of fetuin-A with risk of diabetes and investigated the role of liver fat in this association.
Methods: We conducted a case-cohort study nested in the Multi-Ethnic Study of Atherosclerosis among 1,957 subcohort members and 455 cases (265 of whom belonged to the subcohort) with follow-up from 2000-2012. Fetuin-A was measured from baseline plasma samples by enzyme-linked immunosorbent assay, and liver fat was assessed via computed tomography. Associations were estimated using multivariable-adjusted Cox models, with weighting to account for the case-cohort design.
Results: The association of fetuin-A with risk of diabetes differed between women and men (p-interaction = 0.001). Each standard deviation (SD) higher fetuin-A concentration (0.10 g/L) was associated with a hazard ratio (HR) of 1.51 (95% CI: 1.32-1.74, p <0.0001) among women and an HR of 1.12 (95% CI: 0.94-1.32, p = 0.20) among men. With additional adjustment for liver fat, associations were slightly attenuated in both women (HR per SD fetuin-A = 1.37, 95% CI: 1.19-1.59, p<0.0001) and men (HR = 1.06, 95% CI: 0.90-1.24, p = 0.40). Additional adjustment for other clinical variables had minimal impact on multivariable-adjusted estimates (Figure). Associations did not differ by degree of liver fat content (p-heterogeneity >0.25 for both women and men).
Conclusions: Fetuin-A was associated with diabetes risk, particularly in women, even after adjustment for liver fat.
Author Disclosures: S.A. Aroner: None. K.J. Mukamal: None. D.E. St-Jules: None. M.J. Budoff: None. R. Katz: None. M.H. Criqui: None. M.A. Allison: None. I.H. de Boer: None. D.S. Siscovick: None. J.H. Ix: None. M.K. Jensen: None.
- © 2015 by American Heart Association, Inc.