Abstract
AimSerum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults.MethodsWe conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS.ResultsDuring 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094–2.785) in men and 2.156 (95% CI 1.738–2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229–1.326) in men and 1.366 (95% CI 1.288–1.447) in women.ConclusionsIncreases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.
Highlights
We evaluated the association between percent change in bilirubin and risk of incident Metabolic syndrome (MetS)
Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR)
Increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 in men and 2.156 in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index
Summary
Metabolic syndrome (MetS) is a constellation of interlinked metabolic conditions that seem to accelerate the development of cardiovascular disease [1,2,3]. Bilirubin is the end product of heme catabolism, and a potent endogenous anti-oxidant [5] It reflects serum antioxidant capacity [6]. It exerts a protective effect against inflammatory processes in blood vessels [6,7]. In line with these findings, serum bilirubin concentration has been found to be inversely associated with oxidative stress-related disorders such as cardiovascular diseases, diabetes mellitus, obesity, and MetS [1,6,8,9,10]. A previous study reported an inverse association between mean bilirubin concentrations and the number of metabolic syndrome components in a population with atherogenic dyslipidemia [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
