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

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 μmol/L (interquartile range 2.8–7.7 μmol/L) vs 3.6 (2.3–5.7 μmol/L); P P P P P 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.