title: Fetuin-A and Risk of Diabetes Independent of Liver Fat Content: The Multi-Ethnic Study of Atherosclerosis.
abstract: Fetuin-A is a hepatic secretory protein and a novel risk factor for diabetes. However, it remains unclear whether the association between high levels of fetuin-A and diabetes can be attributed to nonalcoholic fatty liver disease. We conducted a case-cohort study among 1,957 subcohort members and 455 incident diabetes cases in the Multi-Ethnic Study of Atherosclerosis, a multicenter US study of Caucasian, African-American, Hispanic, and Chinese-American adults aged 45-84 years. Serum fetuin-A and computed tomography-determined liver fat content were measured from samples collected at baseline (2000-2002). In multivariable Cox proportional hazards models with follow-up through 2012, a higher fetuin-A level was associated with a higher risk of diabetes, with a stronger association among women (for top quartile vs. bottom, hazard ratio (HR) = 3.36, 95% confidence interval (CI): 2.08, 5.44) than among men (HR = 1.47, 95% CI: 0.93, 2.35) (P-heterogeneity = 0.001). Adjustment for liver fat content attenuated these associations slightly (women: HR = 2.61, 95% CI: 1.59, 4.26; men: HR = 1.32, 95% CI: 0.84, 2.08). In this study, we observed a particularly strong association of fetuin-A with diabetes risk in women that could not be explained by liver fat.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Aroner
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.forename: David E
authors.initials: DE
authors.lastname: St-Jules
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.forename: Michael H
authors.initials: MH
authors.lastname: Criqui
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Allison
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017677:Age Distribution; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis; D001213:Asian / Q000706:statistics & numerical data; D015415:Biomarkers / Q000097:blood; D001741:Black or African American / Q000706:statistics & numerical data; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000208:ethnology / Q000209:etiology; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D015994:Incidence; D015337:Multicenter Studies as Topic; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000208:ethnology; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D000095223:White
chemical_list: D060749:alpha-2-HS-Glycoprotein; D015415:Biomarkers
keywords: biological markers; diabetes mellitus; fatty liver disease, non-alcoholic; fetuins