Molecular Aspects of Lifestyle and Environmental Effects in Patients With Diabetes: JACC Focus Seminar.

Diabetes is characterized as an integrated condition of dysregulated metabolism across multiple tissues, with well-established consequences on the cardiovascular system. Recent advances in precision phenotyping in biofluids and tissues in large human observational and interventional studies have afforded a unique opportunity to translate seminal findings in models and cellular systems to patients at risk for diabetes and its complications. Specifically, techniques to assay metabolites, proteins, and transcripts, alongside more recent assessment of the gut microbiome, underscore the complexity of diabetes in patients, suggesting avenues for precision phenotyping of risk, response to intervention, and potentially novel therapies. In addition, the influence of external factors and inputs (eg, activity, diet, medical therapies) on each domain of molecular characterization has gained prominence toward better understanding their role in prevention. Here, the authors provide a broad overview of the role of several of these molecular domains in human translational investigation in diabetes.