title: Circulating alanine transaminase (ALT) and γ-glutamyl transferase (GGT), but not fetuin-A, are associated with metabolic risk factors, at baseline and at two-year follow-up: the prospective Cyprus Metabolism Study.
abstract: OBJECTIVE
  To comparatively evaluate traditional liver tests and fetuin A as predictors of cardiometabolic risk, we studied associations between serum alanine transaminase (ALT), γ-glutamyl transferase (GGT), aspartate aminotransferase (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters cross-sectionally at baseline, and prospectively, after 2-years of follow-up.
  
  
  METHODS
  616 randomly enrolled young healthy participants in the Cyprus Metabolism Study, including all 93 subjects who participated in the follow-up study 2 years after baseline assessment, were included in this study.
  
  
  RESULTS
  In the cross-sectional study, serum ALT and GGT were strongly correlated with anthropometric, cardiovascular, and metabolic variables, while serum AST was only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was correlated with anthropometric variables, systolic blood pressure (SBP), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) in the unadjusted model. In the fully adjusted model, both serum ALT and GGT levels remained positively correlated with total and low-density lipoprotein (LDL) cholesterol. GGT levels also remained correlated with triglycerides. ALT levels remained strongly positively correlated with insulin (r=0.17, p<.0001) and HOMA-IR (r=0.16, p=0.0001). Serum fetuin-A levels were no longer significantly correlated with any variables. Prospectively, ALT and GGT were predictors of anthropometric variables and LDL cholesterol, while baseline levels of AST and fetuin-A were not predictors of any variables at 2-year follow-up.
  
  
  CONCLUSIONS
  We confirmed associations of ALT and GGT levels but failed to demonstrate an independent association between fetuin-A and cardiometabolic risk factors in young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A predictors of metabolic risk factors cross-sectionally and prospectively in young healthy adults.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Ole-Petter R
authors.initials: OP
authors.lastname: Hamnvik
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Boston, MA.
authors.forename: John P
authors.initials: JP
authors.lastname: Chamberland
authors.affiliation: Cyprus International Institute for Environmental and Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.
authors.forename: Michael
authors.initials: M
authors.lastname: Petrou
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Gong
authors.affiliation: Cyprus International Institute for Environmental and Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus; Department of Environmental Health, Harvard School of Public Health, Boston, MA.
authors.forename: Costas A
authors.initials: CA
authors.lastname: Christophi
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA. Electronic address: skales@hsph.harvard.edu.
authors.forename: Stefanos N
authors.initials: SN
authors.lastname: Kales
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Environmental Health, Harvard School of Public Health, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Boston, MA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003535:Cyprus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D008078:Cholesterol, LDL; D060749:alpha-2-HS-Glycoprotein; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Insulin resistance; Metabolic syndrome; Obesity
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