RT Journal Article SR Electronic T1 Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: an ACCORD trial post hoc analysis JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e000718 DO 10.1136/bmjdrc-2019-000718 VO 7 IS 1 A1 Andrea Cardona A1 Aaron O'Brien A1 Matthew C Bernier A1 Arpad Somogyi A1 Vicki H Wysocki A1 Suzanne Smart A1 Xin He A1 Giuseppe Ambrosio A1 Willa Ann Hsueh A1 Subha V Raman YR 2019 UL http://drc.bmj.com/content/7/1/e000718.abstract AB Introduction Type 2 diabetes mellitus (T2D) confers high atherosclerotic cardiovascular disease (ASCVD) risk. The metabolite trimethylamine N-oxide (TMAO) derived via gut flora has been linked to excess ASCVD.Research design and methods We analyzed data, biospecimens, and major adverse cardiovascular events (MACEs) from the prospective multicenter randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess its value in 330 high-risk individuals with T2D without evident atherosclerotic disease at enrollment.Results Incident cardiovascular events occurred in 165 cases; 165 controls matched by age, sex, and treatment arm experienced no incident events during follow-up. Cases and controls (mean age 64.5 years) had similar mean glycated hemoglobin (HbA1c) (8.2%) and mean 10-year ASCVD risk (23.5%); groups also had similar use of statins and antihypertensive medications at baseline and follow-up. Baseline plasma TMAO levels did not differ between groups after adjusting for ASCVD risk score, HbA1c, and estimated glomerular filtration rate, nor did TMAO distinguish patients suffering incident MACE from those who remained event-free.Conclusions TMAO’s prognostic value for incident ASCVD events may be blunted when applied to individuals with T2D with poor glycemic control and high baseline ASCVD risk. These results behoove further translational investigations of unique mechanisms of ASCVD risk in T2D.