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Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women

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Abstract

Serum total bilirubin (TB) is a potent antioxidant and inversely associated with metabolic syndrome (MetS) in Asian populations. However, there has been no study which is aimed to investigate whether TB is a risk factor for MetS or not. We investigated cross-sectional and longitudinal associations between TB and MetS in 2,435 Japanese men and 1,436 Japanese women. The odds ratios [95 % confidence interval (CI)] of coexisting MetS for each 1 SD increase in log TB were 0.850 (0.754–0.958) (p = 0.008) in men and 0.809 (0.656–0.998) (p = 0.047) in women adjusted for sex, age, smoking, and other confounding covariates. Those for the third and fourth quartiles of TB compared with the lowest quartile were 0.720 (0.537–0.965) (p = 0.028) and 0.737 (0.530–1.052) (p = 0.095), respectively, in men and 0.822 (0.473–1.427) (p = 0.486) and 0.704 (0.362–1.369) (p = 0.301), respectively, in women. There was a tendency that TB and MetS changed inversely to each other. The similarly adjusted hazard ratios of developing MetS for each 1 SD increase in log TB and for the higher quartiles of TB compared with the lowest quartile were not significant either in men or in women. TB is inversely associated with MetS but not a risk factor for MetS in Japanese men and women.

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References

  1. Oda E (2012) Metabolic syndrome: its history, mechanisms, and limitations. Acta Diabetol 49:89–95

    Article  PubMed  CAS  Google Scholar 

  2. World Health Organization (1999) Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO Consultation. World Health Org, Geneva

    Google Scholar 

  3. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) 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

    Article  Google Scholar 

  4. Alberti KGMM, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23:469–480

    Article  PubMed  CAS  Google Scholar 

  5. Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: a statement for health care professionals: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  6. Alberti KG, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome. A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645

    Article  PubMed  CAS  Google Scholar 

  7. Kahn R, Buse J, Ferrannini E, Stern M (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28:2289–2304

    Article  PubMed  Google Scholar 

  8. Simmons RK, Alberti KG, Gale EA et al (2010) The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia 53:600–605

    Article  PubMed  CAS  Google Scholar 

  9. Oda E (2008) The metabolic syndrome as a concept of adipose tissue disease. Hypertens Res 31:1283–1291

    Article  PubMed  CAS  Google Scholar 

  10. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259:87–91

    Article  PubMed  CAS  Google Scholar 

  11. Cinti S, Mitchell G, Barbatelli G et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355

    Article  PubMed  CAS  Google Scholar 

  12. Ridker PM, Wilson PWF, Grandy SM (2004) Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 109:2818–2825

    Article  PubMed  CAS  Google Scholar 

  13. Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37:1595–1607

    Article  PubMed  CAS  Google Scholar 

  14. Kim J, Montagnani M, Koh KK, Quon MJ (2006) Reciprocal relationships between insulin resistance and endothelial dysfunction. Molecular and pathophysiological mechanisms. Circulation 113:1888–1904

    Article  PubMed  Google Scholar 

  15. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  16. Wu TW, Fung KP, Yang CC (1994) Unconjugated bilirubin inhibits the oxidation of human low-density lipoprotein better than Trolox. Life Sci 54:477–481

    Google Scholar 

  17. Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH (2009) Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci USA 106:5171–5176

    Article  PubMed  CAS  Google Scholar 

  18. Frei B, Stocker R, Ames BN (1988) Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 85:9748–9752

    Article  PubMed  CAS  Google Scholar 

  19. Vítek L, Schwertner HA (2007) The heme catabolic pathway and its protective effects on oxidative stress-mediated diseases. Adv Clin Chem 43:1–57

    Article  PubMed  Google Scholar 

  20. Lin LY, Kuo HK, Hwang JJ et al (2009) Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 203:563–568

    Article  PubMed  CAS  Google Scholar 

  21. Wu Y, Li M, Xu M et al (2011) Low serum total bilirubin concentrations are associated with increased prevalence of metabolic syndrome in Chinese. J Diabetes 3:217–224

    Article  PubMed  CAS  Google Scholar 

  22. Choi SH, Yun KE, Choi HJ (2011) Relationships between serum total bilirubin levels and metabolic syndrome in Korean adults. Nutr Metab Cardiovasc [Epub ahead of print]. doi:10.1016/j.numecd.2011.03.001

  23. Kwon KM, Kam JH, Kim MY et al (2011) Inverse association between total bilirubin and metabolic syndrome in rural Korean women. J Womens Health (Larchmt) 20:963–969

    Article  Google Scholar 

  24. Maruhashi T, Soga J, Fujimura N et al (2012) Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in gilbert syndrome. Circulation 126:598–603

    Article  PubMed  CAS  Google Scholar 

  25. Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, Williams RR (1996) Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. Arterioscler Thromb Vasc Biol 16:250–255

    Article  PubMed  CAS  Google Scholar 

  26. Troughton JA, Woodside JV, Young IS et al (2007) Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Eur J Cardiovasc Prev Rehabil 14:79–84

    Article  PubMed  Google Scholar 

  27. Oda E, Kawai R (2012) A possible cross-sectional association of serum total bilirubin with coronary heart disease and stroke in a Japanese health screening population. Heart Vessel 27:29–36

    Article  Google Scholar 

  28. Oda E, Kawai R (2011) Bilirubin is negatively associated with hemoglobin a(1c) independently of other cardiovascular risk factors in apparently healthy Japanese men and women. Circ J 75:190–195

    Article  PubMed  CAS  Google Scholar 

  29. Fukui M, Tanaka M, Shiraishi E et al (2008) Relationship between serum bilirubin and albuminuria in patients with type 2 diabetes. Kidney Int 74:1197–1201

    Article  PubMed  CAS  Google Scholar 

  30. Kuwano T, Miura S, Shirai K et al (2011) Serum levels of bilirubin as an independent predictor of coronary in-stent restenosis: a new look at an old molecule. J Atheroscler Thromb 18:574–583

    Article  PubMed  CAS  Google Scholar 

  31. Huang SS, Huang PH, Leu HB, Wu TC, Lin SJ, Chen JW (2010) Serum bilirubin predicts long-term clinical outcomes in patients with cardiac syndrome X. Heart 96:1227–1232

    Article  PubMed  CAS  Google Scholar 

  32. Oda E, Aoyagi R, Aizawa Y (2012) Hypobilirubinemia might be a possible risk factor of end-stage kidney disease independently of estimated glomerular filtration rate. Kidney Blood Press Res 36:47–54

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank all subjects who participated in the study and the paramedical staff at our center who assisted with the study. The authors received no financial support for this study and have no conflict of interest to disclose.

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Authors and Affiliations

  1. Medical Check-up Center, Tachikawa Medical Center, Nagachou 2-2-16, Nagaoka, Niigata, 940-0053, Japan

    Eiji Oda

  2. Department of Research and Development, Tachikawa Medical Center, Nagaoka, Japan

    Yoshifusa Aizawa

Authors
  1. Eiji Oda
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  2. Yoshifusa Aizawa
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Correspondence to Eiji Oda.

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Communicated by Guido Pozza.

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Oda, E., Aizawa, Y. Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women. Acta Diabetol 50, 417–422 (2013). https://doi.org/10.1007/s00592-012-0447-5

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  • DOI: https://doi.org/10.1007/s00592-012-0447-5

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