Bilirubin as a Potential Causal Factor in Type 2 Diabetes Risk: A Mendelian Randomization Study

Author:

Abbasi Ali123,Deetman Petronella E.2,Corpeleijn Eva1,Gansevoort Ron T.2,Gans Rijk O.B.2,Hillege Hans L.1,van der Harst Pim456,Stolk Ronald P.1,Navis Gerjan2,Alizadeh Behrooz Z.1,Bakker Stephan J.L.2

Affiliation:

1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

2. Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

3. Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Addenbrooke’s Hospital, Cambridge, U.K.

4. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

5. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

6. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands

Abstract

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (age 28–75 years; women 52.6%). We used rs6742078 located in the uridine diphosphate–glucuronosyltransferase locus as an instrumental variable (IV) to study a potential causal effect of serum total bilirubin level on T2D risk. T2D developed in a total of 210 participants (6.2%) during a median follow-up period of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P < 1 × 10−122) and was also associated with T2D risk (odds ratio [OR] 0.69 [95% CI 0.54–0.90]; P = 0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95% CI 0.62–0.92]; P = 0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal OR for IV estimation per 1-SD increase in log-transformed bilirubin 0.58 [95% CI 0.39–0.84]; P = 0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman χ2 test, P for difference = 0.19). These novel results provide evidence that an elevated bilirubin level is causally associated with the risk of T2D and support its role as a protective determinant.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

Cited by 94 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3