Extracellular vesicle-shuttled miRNAs: A critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease causing the development of a large range of cardiovascular (CV) complications. Lifestyle changes and pharmacological therapies only partially halt T2DM progression, and existing drugs are unable to completely suppress the increased CV risk of T2DM patients. Extracellular vesicles (EV)s are membrane-coated nanoparticles released by virtually all living cells and are emerging as novel mediators of T2DM and its CV complications. As a matter of fact, several preclinical models suggest a key involvement of EVs in the initiation and/or progression of insulin resistance, β-cell dysfunction, diabetic dyslipidaemia, atherosclerosis, and other T2DM complications. In addition, preliminary findings also suggest that EV-associated molecular cargo, and in particular the miRNA repertoire, may provide with useful diagnostic and/or prognostic information for the management of T2DM. Here, we review the latest findings showing that EV biology is altered during the entire trajectory of T2DM, i.e. from diagnosis to development of CV complications. We also critically highlight the potential of this emerging research field, by describing both preclinical and clinical observations, and the limitations that must be overcome to translate the preclinical findings into the development of EV-based nano-diagnostic and/or nano-therapeutic tools. Finally, we summarize how two lifestyle changes known to prevent or limit T2DM, i.e. diet and exercise, affect EV number and composition, with a focus on the possible role of EVs contained in food in shaping metabolic responses, a promising approach still in its infancy.