Evidence map›Paper›PMID 27864387›Full record

ArticleClinical chemistry2017

Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.

W H Wilson Tang, Zeneng Wang, Xinmin S Li, Yiying Fan, Daniel S Li, Yuping Wu, Stanley L Hazen

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 14 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 14 syntheses or guidelines pooled it, 230 citations in OpenAlex.

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  15. Gut microbiota-generated trimethylamineAmerican journal of physiology. Endocrinology and metabolism · 2026
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

W H Wilson TangCenter for Cardiovascular Diagnostics & Prevention, Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Zeneng WangCenter for Cardiovascular Diagnostics & Prevention, Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Xinmin S LiCenter for Cardiovascular Diagnostics & Prevention, Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Yiying FanDepartment of Mathematics, Cleveland State University, Cleveland, OH.
Daniel S LiCleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH.
Yuping WuDepartment of Mathematics, Cleveland State University, Cleveland, OH.
Stanley L HazenCenter for Cardiovascular Diagnostics & Prevention, Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; hazens@ccf.org.
Cleveland Clinic Lerner College of Medicine · USCleveland Clinic · USCleveland State University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Structural Determinants Of Ceruloplasmin Inflammatory ActivityP01HL076491 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2004 to 2019
$27.3M
Regression of Atherosclerosis CoreP01HL098055 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FISHER, EDWARD A · 2010 to 2014
$12.1M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
Nitrative stress in heart failureR01HL103931 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI TANG, WAI HONG WILSON · 2010 to 2014
$3.8M
Dietary Choline, Gut Microbiota, and Susceptibility for Chronic Kidney DiseaseR01DK106000 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2015 to 2018
$2.8M
NCATS NIH HHS UL1 TR000439NHLBI NIH HHS P01 HL076491NHLBI NIH HHS P01 HL098055NHLBI NIH HHS P20 HL113452NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL103931NIDDK NIH HHS R01 DK106000
6 · The paper itself

Abstract

backgroundRecent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a proatherogenic 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.

methodsWe examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216 stable patients with T2DM who underwent elective diagnostic coronary angiography.

resultsTMAO [4.4 μmol/L (interquartile range 2.8-7.7 μmol/L) vs 3.6 (2.3-5.7 μmol/L); P < 0.001] and choline concentrations were higher in individuals with T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac event 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, glycohemoglobin, 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].

conclusionsFasting plasma concentrations of the proatherogenic 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.

Indexed as

AgedBetaineBlood GlucoseCholineCohort StudiesDiabetes Mellitus, Type 2FemaleHumansMaleMethylaminesMiddle AgedProspective StudiesRisk FactorsSurvival RateBetaineBlood GlucoseCholineMethylaminestrimethyloxamine

Identifiers

PMID27864387
PMCPMC5659115
OpenAlexW2552933452

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.