Branched-chain amino acids and trimethylamine N-oxide as biomarkers of cardiometabolic outcomes

The identification of biomarkers that could improve the individual risk prediction of developing cardiometabolic disease is one of the salient goals of the 21th century paradigm in medicine captured as precision medicine. Branched-chain amino acids (BCAA) and trimethylamine N-oxide (TMAO) are novel biomarkers linked to key cardiometabolic features, such as insulin resistance, microbiome response to diet, kidney function, and atherogenesis.
In this thesis, we studied the potential role of BCAA and TMAO in the context of cardiometabolic disease. We characterized the association of BCAA with the development of T2D, hypertension, and progression of non-alcoholic fatty liver disease (NAFLD). Moreover, we depicted the clinical impact of TMAO in the risk of cardiovascular and all-cause mortality in patients with T2D and NAFLD; as well as kidney graft failure in post- transplant recipients.
Overall, the results of this thesis support the concept that BCAA and TMAO provide valuable information that can be used to perform a better risk assessment of the early development of cardiometabolic disease, such as hypertension, TD2 and its complications. Given the nature of BCAA and TMAO, these results also pave the way for future studies of pharmacological and non-pharmacological interventions as strategies to mitigate the deleterious consequences of the still-growing pandemic of obesity and T2D. Finally, this thesis also reinforces the idea that it is possible and desirable to apply novel statistical methods that cope with the advanced methods of metabolites quantification, in order to better understand the underlying complexity of T2D and cardiometabolic disease.