title: Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome.
abstract: OBJECTIVE
  Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults.
  
  
  METHODS
  We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS.
  
  
  RESULTS
  During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women.
  
  
  CONCLUSIONS
  Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: You-Bin
authors.initials: YB
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Seung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Jun
authors.affiliation: Department of Health Promotion Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Jee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, MasanHoiwon-gu, Changwon-si, Gyeongsangnam-do, Republic of Korea.
authors.forename: Ji Cheol
authors.initials: JC
authors.lastname: Bae
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Sang-Man
authors.initials: SM
authors.lastname: Jin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.|Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D001663:Bilirubin