Advances in Metabolomics: A Comprehensive Review of Type 2 Diabetes and Cardiovascular Disease Interactions

Type 2 diabetes (T2D) and cardiovascular diseases (CVDs) are major public health challenges worldwide. Metabolomics, the exhaustive assessment of metabolites in biological systems, offers important understanding regarding metabolic disturbances related to these disorders. Recent advances towards integration of metabolomics into clinical practice to facilitate the discovery of novel biomarkers that can improve diagnosis, prognosis, and treatment of T2D and CVDs are discussed in this review. Metabolomics offers potential to characterize key metabolic alterations associated with disease pathophysiology and treatment. T2D is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms, and therefore disease-causing pathways of T2D have not been completely understood. Recent studies have identified several robust clusters of T2D variants representing biologically meaningful distinct pathways, beta cell and proinsulin cluster related to pancreatic insulin secretion, obesity, lipodystrophy, liver/lipid cluster, glycemia, blood pressure and metabolic syndrome clusters representing different pathways causing insulin resistance. For CVDs, recent studies have allowed the metabolomic profile to delineate pathways that contribute to atherosclerosis and heart failure, as well as to the development of targeted therapy. It also covers the role of metabolomics in integrated metabolic genomics and other omics platforms to better understand disease mechanisms, and the transition towards precision medicine. This review further investigates the use of metabolomics in multi-metabolite modelling to enhance risk prediction models for the first occurrence of major adverse cardiovascular events among the individuals with T2D highlighting the value of such approaches in optimizing preventive and therapeutic models in clinical practice.