title: Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: a 4 year retrospective longitudinal study.
abstract: OBJECTIVE
  Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men.
  
  
  METHODS
  This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method.
  
  
  RESULTS
  During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30-2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48-0.99, P for trend = 0.041).
  
  
  CONCLUSIONS
  The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Kang
authors.forename: Jenie Yoonoo
authors.initials: JY
authors.lastname: Hwang
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Jang
authors.forename: Jaechan
authors.initials: J
authors.lastname: Leem
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Hong-Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012016:Reference Values; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; D001663:Bilirubin
keywords: ALT; AST; Antioxidant; BMI; BP; Bilirubin; CVD; FPG; GGT; HDL-C; HMOX; HOMA-IR; HbA1c; LDL-C; NHANES; National Health and Nutrition Examination Surveys; RR; TG; TSH; Type 2 diabetes; WC; alanine aminotransferase; aspartate aminotransferase; blood pressure; body mass index; cardiovascular disease; fasting plasma glucose; gamma-glutamyltransferase; heme oxygenase; hemoglobin A1c; high sensitive C-reactive protein; high-density lipoprotein cholesterol; homeostasis model assessment of insulin resistance; hsCRP; low-density lipoprotein cholesterol; relative risk; thyroid stimulating hormone; triglycerides; waist circumference