PMID- 30868721 OWN - NLM STAT- MEDLINE DCOM- 20200427 LR - 20200427 IS - 1467-789X (Electronic) IS - 1467-7881 (Linking) VI - 20 IP - 6 DP - 2019 Jun TI - Gut microbe-generated metabolite trimethylamine N-oxide and the risk of diabetes: A systematic review and dose-response meta-analysis. PG - 883-894 LID - 10.1111/obr.12843 [doi] AB - Elevated circulating concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) were found in patients with type 2 diabetes mellitus (T2DM). However, whether a high level of TMAO is related to the risk of diabetes has not been studied. We aimed to synthesize the evidence on the relation between TMAO levels and the risk of diabetes mellitus (DM) and to investigate the association further in a dose-response meta-analysis. PubMed, Web of Science, and Scopus databases were searched for studies from inception to June 2018. A total of 12 clinical studies were included in this study, and 15 314 enrolled subjects were included. A meta-analysis of two-class variables and continuous variables were used to obtain pooled effects. Dose-response meta-analysis was used to investigate the dose-response relationship between TMAO concentrations and the risk of DM. Meta-regression and subgroup analyses were applied to identify the source of heterogeneity in this study. High levels of circulating TMAO were associated with an increased risk of DM (odds ratio [OR] = 1.89) using the two-class meta-analysis. Plasma levels of TMAO in patients with diabetes were higher than in subjects without diabetes (standardized mean difference [SMD]: 0.36) using a meta-analysis of continuous variables. The OR for DM prevalence increased by 54% per 5 mumol L(-1) increment of plasma TMAO (OR = 1.54) according to the dose-response meta-analysis. This is the first systematic review and meta-analysis to demonstrate a positive dose-dependent association between circulating TMAO levels and increased diabetes risk. CI - (c) 2019 World Obesity Federation. FAU - Zhuang, Rulin AU - Zhuang R AUID- ORCID: 0000-0003-4557-4289 AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Ge, Xinyu AU - Ge X AUID- ORCID: 0000-0001-7579-1044 AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Han, Lu AU - Han L AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Yu, Ping AU - Yu P AD - Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. FAU - Gong, Xin AU - Gong X AD - Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. FAU - Meng, Qingshu AU - Meng Q AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Zhang, Yuzhen AU - Zhang Y AUID- ORCID: 0000-0002-9570-1269 AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Fan, Huimin AU - Fan H AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. FAU - Zheng, Liang AU - Zheng L AUID- ORCID: 0000-0002-2113-0117 AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Liu, Zhongmin AU - Liu Z AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. FAU - Zhou, Xiaohui AU - Zhou X AUID- ORCID: 0000-0002-9354-3789 AD - Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. AD - Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20190313 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Methylamines) RN - FLD0K1SJ1A (trimethyloxamine) SB - IM MH - Diabetes Mellitus, Type 2/*blood/*epidemiology MH - Gastrointestinal Microbiome/*physiology MH - Humans MH - Methylamines/*blood MH - Risk Factors OTO - NOTNLM OT - diabetes OT - dose-response meta-analysis OT - risk OT - trimethylamine N-oxide (TMAO) EDAT- 2019/03/15 06:00 MHDA- 2020/04/28 06:00 CRDT- 2019/03/15 06:00 PHST- 2018/11/27 00:00 [received] PHST- 2019/01/31 00:00 [revised] PHST- 2019/01/31 00:00 [accepted] PHST- 2019/03/15 06:00 [pubmed] PHST- 2020/04/28 06:00 [medline] PHST- 2019/03/15 06:00 [entrez] AID - 10.1111/obr.12843 [doi] PST - ppublish SO - Obes Rev. 2019 Jun;20(6):883-894. doi: 10.1111/obr.12843. Epub 2019 Mar 13.