Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: a 4 year retrospective longitudinal study

Metabolism. 2014 Jan;63(1):87-93. doi: 10.1016/j.metabol.2013.09.011. Epub 2013 Oct 18.


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.

Materials and 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.

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.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bilirubin / blood*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Humans
  • Incidence
  • Insulin Resistance
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Reference Values
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Triglycerides / blood


  • Blood Glucose
  • Triglycerides
  • Bilirubin