Serum bilirubin levels predict future development of metabolic syndrome in healthy middle-aged nonsmoking men

Background Despite epidemiologic research demonstrating an inverse relationship between serum bilirubin levels and the prevalence of metabolic syndrome, prospective data on serum bilirubin as a predictor of incident metabolic syndrome are limited. Methods Serum bilirubin was examined as a risk marker for incident metabolic syndrome in a prospective study of 468 Taiwanese middle-aged men who were free of metabolic syndrome and other systemic diseases at baseline. These subjects were followed up in annual health examinations between 2001 and 2009 for the development of metabolic syndrome, which was defined according to unified criteria set by several major organizations. Results Among the study subjects, 377 were nonsmokers and 91 were current smokers. All individuals were then stratified into 3 groups according to their baseline serum bilirubin levels (low, normal, and high). During a mean follow-up period of 7.58 years, 66 subjects developed metabolic syndrome. The incidence of metabolic syndrome was significantly reduced in the high-bilirubin group compared with the low-bilirubin group (6.4% vs 22.4%, P <.001). Multivariate Cox regression analysis revealed that the hazard ratio for incident metabolic syndrome between the highest and lowest tertiles of serum bilirubin levels was 0.246 (95% confidence interval 0.120-0.503). However, although it remained clearly evident in nonsmokers, the inverse correlation was attenuated in current smokers. Conclusions Increased serum bilirubin was associated with a reduced future risk of metabolic syndrome in apparently healthy middle-aged, nonsmoking men. Our findings support the predictive role of serum total bilirubin for future development of metabolic syndrome.