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Diabetes: Many Faces of the Disease | EK18


EK18-eposter-flores-guerrero-jose - Circulating Trimethylamine N-Oxide is associated with increased risk of cardiovascular mortality in type 2 diabetes: Results from a Dutch Diabetes Cohort.


Feb 1, 2021 12:00am ‐ Feb 1, 2021 12:00am

Description

Circulating Trimethylamine N-Oxide is associated with increased risk of cardiovascular mortality in type 2 diabetes: Results from a Dutch Diabetes Cohort. Authors and Affiliations Jose L. Flores-Guerrero1, Peter R. van Dijk2,3, Margery A. Connelly4, Erwin Garcia4, Henk J.G. Bilo5, Gerjan Navis1, Robin P.F. Dullaart2, Stephan J.L. Bakker1 1 Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2 Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3 Diabetes Centre, Isala, Zwolle, The Netherlands. 4 Laboratory Corporation of America Holdings (LabCorp), Morrisville, North Carolina, USA. 5 Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands. Correspondence: j.l.flores.guerrero@umcg.nl Abstract. Background. Trimethylamine N-oxide (TMAO), a gut microbiome–derived metabolite, has been proposed as a risk factor for cardiovascular (CV) disease and mortality in the general population. Furthermore, it has been proposed that branched chain amino acids (BCAA) concentrations are affected by microbiota, as well. The association of TMAO with CV mortality in Type 2 Diabetes (T2D) and its determinants remain unclear. Therefore, the objective of our study was to investigate the association of plasma TMAO concentrations with CV mortality in individuals with T2D and to evaluate the association between BCAA and TMAO. Methods. Data of 595 participants from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort were analysed. Plasma TMAO and BCAA were measured by nuclear magnetic resonance spectroscopy. The risk of CV mortality was estimated using multivariable-adjusted Cox proportional hazards regression models. Results. During a median follow-up of 10 years, 180 participants died, of which 113 from CV disease. In Cox regression analyses, adjusted for age, sex, systolic blood pressure, T2D duration, macrovascular complications, smoking, total cholesterol, HDL cholesterol, triglycerides, BCAAs and albuminuria TMAO was independently associated with CV mortality: HR 2.09 [1.21; 3.60], p = 0.008 (for the highest compared to the lowest tertile of the TMAO distribution). The same was true for analyses with TMAO as continuous variable: HR 1.38 [1.11; 1.70], p = 0.003 (per SD increase). In contrast, BCAAs were not independently associated with increased CV mortality. Conclusions. Higher plasma concentrations of TMAO but not BCAAs are independently associated with an increased risk of CV mortality in individuals with T2D, independent of clinical and biochemical risk markers. Key Words— Trimethylamine-N-oxide; TMAO; Branched Chain Amino Acids; BCAA; Cardiovascular mortality; Bayesian methods

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