Article Text
Abstract
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.
- atherosclerosis
- type 2 diabetes
- risk predictors
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Footnotes
AC and AO are co-first authors.
Contributors AC: study design, biospecimen analysis, data interpretation, data analysis and manuscript writing; AO: biospecimen analysis, data interpretation, data analysis and manuscript writing; MCB: biospecimen analysis, data analysis and manuscript writing; AS: biospecimen analysis, data interpretation and manuscript writing; VHW: data interpretation and manuscript writing; SS: study design, data interpretation, manuscript writing; XH: data analysis and statistical analysis; GA: data interpretation and manuscript writing; WAH: data interpretation and manuscript writing; SVR: study design, biospecimen analysis, data interpretation, data analysis and manuscript writing. SVR, principal investigator, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This work was supported by the US National Center for Advancing Translational Sciences (UL1TR002733).
Competing interests AC was recipient of a grant-in-aid by Fondazione Umberto Veronesi, Italy.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.