Advertisement

Endocrine

, Volume 39, Issue 2, pp 182–189 | Cite as

Total, direct, and indirect serum bilirubin concentrations and metabolic syndrome among the Korean population

  • Jaeseong Jo
  • Ji Eun Yun
  • Heeyeon Lee
  • Heejin Kimm
  • Sun Ha JeeEmail author
Original Article

Abstract

Total bilirubin, not direct or indirect bilirubin, has been reported to associate inversely with metabolic syndrome. Therefore, we aimed to evaluate the association between bilirubin subtypes and metabolic syndrome among the Korean population. This study included 5,231 Koreans (3,008 men, 2,223 women) aged 30–87 years, who visited the Health promotion centers in Seoul from April, 2006 to June, 2007. The associations of direct, indirect, and total bilirubin classified in quartiles with metabolic syndrome were measured by logistic regression analyses in men and women. Odds ratios (95% confidence intervals) of the lowest, 2nd and 3rd quartiles of direct serum bilirubin compared with the highest quartile (reference) were 2.3 (1.6–3.2), 1.8 (1.3–2.4), and 1.8 (1.4–2.4) among men, and 5.5 (2.6–11.5), 3.1 (1.5–6.7), and 1.9 (0.9–4.3) among women, respectively. In a multivariable adjusted model, however, the significance of inverse associations with total and indirect bilirubin became attenuated. The relation was consistent particularly with direct bilirubin in subgroups of metabolic syndrome components such as central obesity, hypertriglyceridemia, hyperglycemia, and low HDL-cholesterol in both men and women. Of the three subtypes of serum bilirubin, the inverse association of metabolic syndrome was significantly apparent and consistent with direct bilirubin.

Keywords

Serum bilirubin Metabolic syndrome 

Notes

Acknowledgments

This study was supported by a grant (10526) from the Seoul City R&BD program and by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0920330).

References

  1. 1.
    R. Stocker, Y. Yamamoto, A.F. McDonagh, A.N. Glazer, B.N. Ames, Bilirubin is an antioxidant of possible physiological importance. Science 235, 1043–1046 (1987)PubMedCrossRefGoogle Scholar
  2. 2.
    T.W. Wu, J. Wu, R.K. Li, D. Mickle, D. Carey, Albumin-bound bilirubins protect hyman ventricular myocytes against oxyradical damage. Biochem. Cell Biol. 69, 683–688 (1991)PubMedCrossRefGoogle Scholar
  3. 3.
    H.A. Schwertner, L. Vitek, Gilbert syndrome, UGT1A1*28 allel, and cardiovascular disease risk: Possible protective effects and therapeutic applications of bilirubin. Atherosclerosis 198, 1–11 (2008)PubMedCrossRefGoogle Scholar
  4. 4.
    S.C. Hunt, F. Kronenberg, J.H. Eckfeldt, P.N. Hopkins, R.H. Myers, G. Heiss, Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: the NHLBI family heart study. Atherosclerosis 154, 747–754 (2001)PubMedCrossRefGoogle Scholar
  5. 5.
    B. Krijgsman, J.A. Papadkis, E.S. Ganotakis, D.P. Mikhailidis, G. Hamilton, The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin. Int. Angiol. 21, 44–52 (2002)PubMedGoogle Scholar
  6. 6.
    D. Erdogan, H. Gullu, E. Yildirim, D. Tok, O. Ciftci, S.T. Baycan, H. Muderrisoglu, Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women. Atherosclerosis 184, 431–437 (2006)PubMedCrossRefGoogle Scholar
  7. 7.
    H.J. Kimm, J.E. Yun, J. Jo, S.H. Jee, Low serum bilirubin level as an independent predictor of stroke incidence: a prospective study in Korean men and women. Stroke 40, 3422–3427 (2009)PubMedCrossRefGoogle Scholar
  8. 8.
    E.S. Ford, A.H. Mokdad, W.H. Giles, D.W. Brown, The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Diabetes 52, 2346–2352 (2003)PubMedCrossRefGoogle Scholar
  9. 9.
    P.M. Gorter, J.K. Olijhoek, Y. van der Graaf, A. Algra, T.J. Rabelink, F.L. Visseren, Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 173, 363–369 (2004)PubMedCrossRefGoogle Scholar
  10. 10.
    M.K. Rutter, J.B. Meigs, L.M. Sullivan, R.B. D’Agostino, P.W. Wilson, C-reactive protein, the metabolic syndrome and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 110, 380–385 (2004)PubMedCrossRefGoogle Scholar
  11. 11.
    J.S. Torgerson, A.K. Lindroos, C.D. Sjostrom, R. Olsson, L. Lissner, L. Sjostrom, Are elevated aminotransferases and decreased bilirubin additional characteristics of the metabolic syndrome? Obes. Res. 5, 105–114 (1997)PubMedGoogle Scholar
  12. 12.
    L.Y. Lin, H.K. Kuo, J.J. Hwang, L.P. Lai, F.T. Chiang, C.D. Tseng, J.L. Lin, Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 203, 563–568 (2009)PubMedCrossRefGoogle Scholar
  13. 13.
    L.H. Bremier, K.A. Spyropolous, A.F. Winder, D.P. Mikhailidis, G. Hamilton, Is bilirubin protective against coronary artery disease? Clin. Chem. 40, 1987–1988 (1994)Google Scholar
  14. 14.
    L.H. Bremier, G. Wannamethee, S. Ebrahim, A.G. Shaper, Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clin. Chem. 41, 1504–1508 (1995)Google Scholar
  15. 15.
    H.A. Schwertner, W.G. Jackson, G. Tolan, Association of Low serum concentration of bilirubin with increased risk of coronary artery disease. Clin. Chem. 40, 18–23 (1994)PubMedGoogle Scholar
  16. 16.
    S. Pineda, O.Y. Bang, J.L. Saver, S. Starkman, S.W. Yun, D.S. Liebeskind, L.K. Ali, S.H. Shah, B. Ovbiagele, Association of serum bilirubin with ischemic stroke outcomes. J. Stroke Cerebrovasc. Dis. 17, 147–152 (2008)PubMedCrossRefGoogle Scholar
  17. 17.
    H.J. Hwang, S.H. Kim, Inverse relationship between fasting direct bilirubin and metabolic syndrome in Korean adults. Clin. Chim. Acta 411, 1496–1501 (2010)PubMedCrossRefGoogle Scholar
  18. 18.
    T. Nakagami, K. Toyomura, T. Kinoshita, S. Morisawa, A beneficial role of bile pigments as an endogenous tissue protector: anticomplement effects of biliverdin and conjugated bilirubin. Biochim. Biophys. Acta 1158, 189–193 (1993)PubMedGoogle Scholar
  19. 19.
    M. Mamtani, A. Patel, R. Renge, H. Kulkarni, Prognostic value of direct bilirubin in neonatal hyperbilirubinemia. Indian J. Pediatr. 74, 819–822 (2007)PubMedCrossRefGoogle Scholar
  20. 20.
    S. Shiomi, D. Habu, T. Kuroki, S. Ishida, N. Tatsumi, Clinical usefulness of conjugated bilirubin levels in patients with acute liver diseases. J. Gastroenterol. 34, 88–93 (1993)CrossRefGoogle Scholar
  21. 21.
    B. Li, Z. Wang, J.J. Fang, C.Y. Xu, W.X. Chen, Evaluation of prognostic markers in severe drug-induced liver disease. World J. Gastroenterol. 13, 628–632 (2007)PubMedGoogle Scholar
  22. 22.
    O. Yavuz, S. Aras, Interaction between serum bilirubin level and lipid profile. T Klin. Tip Bilim. 22, 276–280 (2002)Google Scholar
  23. 23.
    R.J. Simon Maxwell, Y.H. Gregory, Free radicals and antioxidants in cardiovascular disease. Br. J. Clin. Pharmacol. 44, 307–317 (1997)CrossRefGoogle Scholar
  24. 24.
    T.W. Wu, K.P. Fung, C.C. Yang, Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. Life Sci. 54, 477–481 (1994)Google Scholar
  25. 25.
    J. Neuzil, R. Stocker, Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J. Biol. Chem. 269, 16712–16719 (1994)PubMedGoogle Scholar
  26. 26.
    T. Yamaguchi, F. Horio, T. Hashizume, M. Ttanaka, S. Ikeda, A. Kakinuma, H. Nakajima, Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo. Biochem. Biophys. Res. Commun. 4, 11–19 (1995)CrossRefGoogle Scholar
  27. 27.
    T. Aizawa, N. Ishizaka, J. Taguchi, S. Kimura, K. Kurokawa, M. Ohno, Baloon injury does not induce heme oxygenase-1 expression, but administration of hemin inhibits neointimal formation in balloon-injury rat carotid artery. Biochem. Biophys. Res. Commun. 261, 302–307 (1999)PubMedCrossRefGoogle Scholar
  28. 28.
    B. Frei, R. Stocker, B.N. Ames, Antioxidant defenses and lipid peroxidation in human blood plasma. Proc. Natl. Acad. Sci. USA 85, 9748–9752 (1988)PubMedCrossRefGoogle Scholar
  29. 29.
    C. Hammerman, R. Goldstein, M. Kaplan, M. Eran, D. Goldschmidt, A.I. Eidelman, L.M. Gartner, Bilirubin in the premature: toxic waste or natural defense? Clin. Chem. 44, 2551–2553 (1998)PubMedGoogle Scholar
  30. 30.
    F. Armutcu, M. Ataymen, H. Atmaca, A. Gurel, Oxidative stress markers, C-reactive protein and heat shock protein 70 levels in subjects with metabolic syndrome. Clin. Chem. Lab. Med. 46, 785–790 (2008)PubMedCrossRefGoogle Scholar
  31. 31.
    B. Burchell, R. Hume, Molecular genetic basis of Gilbert’s syndrome. J. Gastroenterol. Hepatol. 14, 960–966 (1999)PubMedCrossRefGoogle Scholar
  32. 32.
    S.J. Yoon, H.S. Lee, S.W. Lee, J.E. Yun, S.Y. Kim, E.R. Cho, S.J. Lee, E.J. Jee, H.Y. Lee, J. Park, H.S. Kim, S.H. Jee, The association between adiponectin and diabetes in the Korean population. Metabolism 57, 853–857 (2008)PubMedCrossRefGoogle Scholar
  33. 33.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2486–2497 (2001)Google Scholar
  34. 34.
    S. Inoue, P. Zimmet, I. Caterson, C. Chunming, Y. Ikeda, A.K. Khalid, Y.S. Kim, J. Bassett, The Asia-Pacific perspective: redefining obesity and its treatment. International Obesity Task Force. Western Pacific Region of the World Health Organization (2000)Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jaeseong Jo
    • 1
  • Ji Eun Yun
    • 1
  • Heeyeon Lee
    • 1
  • Heejin Kimm
    • 1
  • Sun Ha Jee
    • 1
    Email author
  1. 1.Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public HealthYonsei UniversitySeoulRepublic of Korea

Personalised recommendations