Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.
Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.
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DOI：
10.1373/clinchem.2016.263640
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发表时间：
2017-01
影响因子：
9.3
通讯作者：
Hazen SL
中科院分区：
文献类型：
--
作者：
Tang WH;Wang Z;Li XS;Fan Y;Li DS;Wu Y;Hazen SL
最近的研究表明，肠道微生物代谢的饮食磷脂酰胆碱和冠状动脉疾病的发病机制之间的联系。促动脉粥样硬化肠道微生物产生的代谢产物，三甲胺N-氧化物（TMAO）的浓度，预测多个队列中心血管疾病风险增加。2型糖尿病（T2 DM）患者的TMAO浓度升高，但其预后价值及其与血糖控制的关系尚不清楚。我们在1,216例接受选择性诊断性冠状动脉造影的稳定型T2 DM患者中研究了空腹TMAO及其两种营养前体物质胆碱和甜菜碱与3年主要不良心脏事件和5年死亡率之间的关系。T2 DM患者的TMAO（4.4 µmol/L [四分位距2.8-7.7µ mol/L] vs. 3.6[2.3-5.7µmol/L]; P<0.001）和胆碱浓度高于健康对照。在T2 DM患者中，血浆TMAO水平升高与3年主要不良心脏事件风险显著增加3.0倍（P<0.001）和5年死亡风险增加3.6倍（P<0.001）相关。在调整传统危险因素和高敏C反应蛋白、糖化血红蛋白和估计的肾小球滤过率后，TMAO浓度升高仍然是T2 DM患者主要不良心脏事件和死亡风险的预测因素（例如四分位数4 vs. 1，风险比分别为2.05[95%CI 1.31-3.20]，P<0.001;和2.07[95%CI 1.37-3.14]，P<0.001）。糖尿病患者中促动脉粥样硬化肠道微生物产生的代谢物TMAO的空腹血浆浓度较高，预示着较高的主要不良心脏事件和死亡风险，与传统风险因素、肾功能和血糖控制的关系无关。
Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a pro-atherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. We examined the relationship between fasting TMAO and two of its nutrient precursors, choline and betaine, versus 3-year major adverse cardiac events and 5-year mortality in 1,216 stable patients with T2DM who underwent elective diagnostic coronary angiography. TMAO (4.4 µmol/L [interquartile range 2.8–7.7µmol/L] vs. 3.6[2.3–5.7µmol/L]; P<0.001) and choline concentrations were higher in individuals with T2DM versus healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac events risk (P<0.001) and a 3.6-fold increased 5-year mortality risk (P<0.001). Following adjustments for traditional risk factors and high sensitivity C-reactive protein, glycated hemoglobin and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients (e.g. Quartiles 4 vs. 1, hazard ratio 2.05[95%CI 1.31–3.20], P<0.001; and 2.07[95%CI 1.37–3.14], P<0.001, respectively). Fasting plasma concentrations of the pro-atherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control.
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DOI：
10.1056/nejmoa1109400
发表时间：
2013-04-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tang WH;Wang Z;Levison BS;Koeth RA;Britt EB;Fu X;Wu Y;Hazen SL
通讯作者：
Hazen SL
影响因子：
3.7
作者：
Lever M;George PM;Elmslie JL;Atkinson W;Slow S;Molyneux SL;Troughton RW;Richards AM;Frampton CM;Chambers ST
通讯作者：
Chambers ST
影响因子：
5
作者：
Danne, Oliver;Lueders, Christian;Moeckel, Martin
通讯作者：
Moeckel, Martin
影响因子：
3.7
作者：
Lever M;George PM;Slow S;Bellamy D;Young JM;Ho M;McEntyre CJ;Elmslie JL;Atkinson W;Molyneux SL;Troughton RW;Frampton CM;Richards AM;Chambers ST
通讯作者：
Chambers ST
DOI：
10.1073/pnas.1215689109
发表时间：
2012-12-26
影响因子：
11.1
作者：
Craciun, Smaranda;Balskus, Emily P.
通讯作者：
Balskus, Emily P.