Elsevier

Diabetes & Metabolism

Volume 40, Issue 4, September 2014, Pages 305-309
Diabetes & Metabolism

Short report
Serum bilirubin as a predictor of incident metabolic syndrome: A 4-year retrospective longitudinal study of 6205 initially healthy Korean men

https://doi.org/10.1016/j.diabet.2014.04.006Get rights and content

Abstract

Aim

Serum bilirubin is an endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with oxidative stress-mediated diseases, including the metabolic syndrome (MetS). However, the clinical relevance of bilirubin as a risk factor for incident MetS remains controversial. For this reason, the longitudinal effects of baseline serum bilirubin concentrations on incident MetS were evaluated in Korean men.

Methods

This 4-year retrospective longitudinal observational study involved 6205 Korean men without MetS. Subjects underwent routine health examinations in 2007 and returned for a follow-up examination in 2011. Baseline serum bilirubin concentrations were determined using the vanadate oxidation method.

Results

During the 4-year period, 936 cases of incident MetS (15.1%) were identified. Its incidence decreased across baseline bilirubin quartile categories (P < 0.001), with an odds ratio (OR) for developing MetS being significantly lower in the highest quartile group (≥ 1.40 mg/dL) compared with the lowest (≤ 0.90 mg/dL) after adjusting for all confounding variables [OR = 0.70, 95% confidence interval (CI) 0.54–0.90; P for trend = 0.019]. Among individual components of MetS, bilirubin was found to be negatively associated with only the risk of incident hypertriglyceridaemia. The OR (95% CI) for incident hypertriglyceridaemia in the highest vs lowest quartile was 0.75 (0.61–0.91; P for trend = 0.002).

Conclusion

Serum total bilirubin level was negatively associated with incidence of MetS in healthy Korean men over a 4-year period.

Introduction

The metabolic syndrome (MetS) is a complex disorder involving a combination of risk factors of metabolic origin that appear to promote the development of cardiovascular disease (CVD) [1]. Chronic inflammation, insulin resistance and oxidative stress are important factors in the initiation and progression of MetS [1].

Bilirubin has been regarded as a potentially toxic metabolite of haem catabolism [2], but recent data have suggested that it has numerous other beneficial effects, such as scavenging excess reactive oxygen species and anti-inflammatory actions [3]. In line with these beneficial effects, mildly elevated bilirubin has been negatively associated with oxidative stress-mediated diseases, including CVD [4] and MetS [5], [6], [7], although most studies were cross-sectional in design.

Recently, Oda et al. [8] reported that total bilirubin was not a risk factor for MetS in a longitudinal study. However, in contrast to that report, our recent longitudinal study of bilirubin and incident type 2 diabetes showed a negative association between bilirubin and waist circumference (WC), fasting plasma glucose (FPG) and hypertriglyceridaemia, which are individual components of MetS [9]. These findings raise the possibility that bilirubin could be a risk factor for MetS. Thus, the longitudinal effects of baseline serum bilirubin concentrations on the incidence of MetS were further investigated over a 4-year follow-up study.

Section snippets

Methods

The study cohort comprised 8068 Korean men who had undergone comprehensive routine health examinations at the Health Screening and Promotion Center of the Asan Medical Center in Seoul, Republic of Korea, in 2007 and who had returned for follow-up examinations in 2011. Of these men, 1674 subjects with MetS were excluded at baseline. In addition, 189 subjects who were missing values for baseline bilirubin level were also excluded. After these exclusions, 6205 men with a mean age of 49.4 years

Results

Subjects were categorized into four quartiles (Q1–Q4) according to baseline total bilirubin concentrations, and their clinical and biochemical characteristics according to bilirubin quartile categories are shown in Table 1. As the bilirubin quartile increased, the prevalence of current smokers and frequent exercisers decreased. On checking the interaction between smoking status and bilirubin to test whether the effect of bilirubin on incident MetS differed according to smoking status, there was

Discussion

In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident MetS, thereby suggesting that mildly elevated bilirubin may play a protective role against incident MetS. Furthermore, serum bilirubin was negatively associated with the risk of incident hypertriglyceridaemia.

Several recent studies have also reported a negative association between bilirubin and MetS [5], [6], [7]. However, most of these studies were

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.
Funding: No funding source is reported.

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1

These authors contributed equally to this work.

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