PMID- 27864387
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20220514
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Print)
IS  - 0009-9147 (Linking)
VI  - 63
IP  - 1
DP  - 2017 Jan
TI  - Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of 
      Glycemic Control in Patients with Type 2 Diabetes Mellitus.
PG  - 297-306
LID - 10.1373/clinchem.2016.263640 [doi]
AB  - BACKGROUND: Recent 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. METHODS: We 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. 
      RESULTS: TMAO [4.4 mumol/L (interquartile range 2.8-7.7 mumol/L) vs 3.6 (2.3-5.7 
      mumol/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]. CONCLUSIONS: Fasting 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.
CI  - (c) 2016 American Association for Clinical Chemistry.
FAU - Tang, W H Wilson
AU  - Tang WH
AD  - Center for Cardiovascular Diagnostics & Prevention, Department of Cellular & 
      Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
AD  - Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland 
      Clinic, Cleveland, OH.
FAU - Wang, Zeneng
AU  - Wang Z
AD  - Center for Cardiovascular Diagnostics & Prevention, Department of Cellular & 
      Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
FAU - Li, Xinmin S
AU  - Li XS
AD  - Center for Cardiovascular Diagnostics & Prevention, Department of Cellular & 
      Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
FAU - Fan, Yiying
AU  - Fan Y
AD  - Department of Mathematics, Cleveland State University, Cleveland, OH.
FAU - Li, Daniel S
AU  - Li DS
AD  - Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 
      Cleveland, OH.
FAU - Wu, Yuping
AU  - Wu Y
AD  - Department of Mathematics, Cleveland State University, Cleveland, OH.
FAU - Hazen, Stanley L
AU  - Hazen SL
AD  - Center for Cardiovascular Diagnostics & Prevention, Department of Cellular & 
      Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; 
      hazens@ccf.org.
AD  - Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland 
      Clinic, Cleveland, OH.
LA  - eng
GR  - R01 HL103931/HL/NHLBI NIH HHS/United States
GR  - R01 DK106000/DK/NIDDK NIH HHS/United States
GR  - R01 HL103866/HL/NHLBI NIH HHS/United States
GR  - P01 HL076491/HL/NHLBI NIH HHS/United States
GR  - P20 HL113452/HL/NHLBI NIH HHS/United States
GR  - P01 HL098055/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000439/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20161118
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Blood Glucose)
RN  - 0 (Methylamines)
RN  - 3SCV180C9W (Betaine)
RN  - FLD0K1SJ1A (trimethyloxamine)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Aged
MH  - Betaine/blood/metabolism
MH  - Blood Glucose/*analysis/metabolism
MH  - Choline/blood/metabolism
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/*blood/diagnosis/metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Methylamines/*blood/metabolism
MH  - Middle Aged
MH  - Prospective Studies
MH  - Risk Factors
MH  - Survival Rate
PMC - PMC5659115
MID - NIHMS913769
EDAT- 2016/11/20 06:00
MHDA- 2017/06/07 06:00
PMCR- 2017/10/27
CRDT- 2016/11/20 06:00
PHST- 2016/07/07 00:00 [received]
PHST- 2016/10/27 00:00 [accepted]
PHST- 2016/11/20 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/11/20 06:00 [entrez]
PHST- 2017/10/27 00:00 [pmc-release]
AID - clinchem.2016.263640 [pii]
AID - 10.1373/clinchem.2016.263640 [doi]
PST - ppublish
SO  - Clin Chem. 2017 Jan;63(1):297-306. doi: 10.1373/clinchem.2016.263640. Epub 2016 
      Nov 18.