Gut microbe–generated metabolite trimethylamine N‐oxide and the risk of diabetes: A systematic review and dose‐response meta‐analysis

Obesity Reviews - Tập 20 Số 6 - Trang 883-894 - 2019
Rulin Zhuang1,2,3, Xinyu Ge1,2,3, Lu Han2,3, Ping Yu4, Xin Gong4, Qingshu Meng2,3, Yuzhen Zhang2,3, Huimin Fan1,4,2,3, Liang Zheng2,3, Zhongmin Liu1,4,2,3, Xiaohui Zhou2,3
1Department of Cardiothoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
2Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
3Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
4Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120 China

Tóm tắt

SummaryElevated 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 μmol 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.

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Tài liệu tham khảo

10.1038/nrendo.2012.236

10.1016/j.diabres.2011.10.029

10.1038/nature18646

10.1038/nature11450

10.1073/pnas.0601056103

10.1016/j.nut.2015.05.006

10.1111/joim.12328

10.1055/s-0035-1569330

10.1016/j.jbiosc.2014.03.001

Shan Z, 2017, Association between microbiota‐dependent metabolite trimethylamine‐N‐oxide and type 2 diabetes, Am J Clin Nutr, 106, 888, 10.3945/ajcn.117.157107

10.1038/nature09922

10.2337/dc14-2093

10.1136/gutjnl-2018-316155

10.1016/j.ijsu.2010.02.007

10.1136/bmj.327.7414.557

10.7326/0003-4819-127-9-199711010-00008

10.1016/S0895-4356(00)00242-0

10.1136/eb-2014-101967

10.1093/aje/kwr265

10.1161/JAHA.115.002816

10.1136/heartjnl-2015-308826

10.3945/ajcn.115.121269

10.1016/j.jacc.2014.02.617

10.1007/s10157-015-1207-y

10.1373/clinchem.2016.263640

10.1038/s41598-017-13739-9

10.1016/j.cjca.2015.06.016

10.1016/j.ijcard.2018.04.126

10.1371/journal.pone.0114969

10.1016/j.atherosclerosis.2015.10.091

10.3389/fmicb.2017.01936

10.1161/ATVBAHA.114.303252

10.1038/nm.3145

10.1021/pr060265y

10.3945/ajcn.114.087692

10.1080/15287399409531853

10.2337/dc11-0442

10.1001/jama.2009.726

10.1172/JCI72331

10.1056/NEJMoa1109400

10.1016/j.atherosclerosis.2013.10.013

10.1093/eurheartj/ehx342

10.1111/jcmm.13307

10.1161/JAHA.116.004947

10.1111/joim.12543

10.3945/an.113.003681

Tong M, 2009, Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 diabetes mellitus, non‐alcoholic steatohepatitis, and Alzheimer's disease, J Alzheimers Dis, 17, 827

10.1186/1750-1326-4-54

10.2174/1381612823666170622095324

10.1038/ncomms7498

10.1152/physrev.00010.2008

10.1016/j.immuni.2016.09.008

10.1074/jbc.M111.248203