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

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 diseas...

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Published in:	Clinical chemistry (Baltimore, Md.) Md.), 2017-01, Vol.63 (1), p.297-306
Main Authors:	Tang, W H Wilson, Wang, Zeneng, Li, Xinmin S, Fan, Yiying, Li, Daniel S, Wu, Yuping, Hazen, Stanley L
Format:	Article
Language:	eng
Subjects:	Aged Betaine - blood Betaine - metabolism Blood Glucose - analysis Blood Glucose - metabolism Choline - blood Choline - metabolism Cohort Studies Coronary heart disease Development and progression Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - diagnosis Diabetes Mellitus, Type 2 - metabolism Dietary supplements Female Health risk assessment Humans Insulin resistance Male Metabolites Methylamines - blood Methylamines - metabolism Microbiota (Symbiotic organisms) Middle Aged Mortality Physiological aspects Prospective Studies Risk Factors Studies Survival Rate Type 2 diabetes
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Summary:	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. 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. TMAO [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]. 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.
ISSN:	0009-9147 1530-8561