Start small, think big: MicroRNAs in diabetes mellitus and relevant cardiorenal-liver metabolic health spectrum

Diabetes mellitus (DM), co-existing with metabolic disorder of cardio-renal-liver, is one of the most difficult problems in medicine that attracts global concern with high mortality. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that negatively regulates gene expression and exerts active against a large proportion of the transcriptome, due to their high evolutionary conservation. Emerging evidence prove that miRNAs are involved in the pathogenesis of DM and associated metabolic disorders, manifested by their variable alteration in the blood, urine, tissues, or organs, principally contributing to modulate the interconnections between DM and cardio-renal-liver metabolism. Mechanistically, miRNAs regulate various biological processes, such as metabolism of insulin, lipid, glucose, inflammatory response, fibrosis, oxidative stress, apoptosis, and angiogenesis, etc. This review emphasizes the function of miRNAs and highlights the physiopathological regulation of miRNA in DM and related complications, especially the dysfunction of cardiovascular system, kidneys, and liver, with the aim of providing promising biomarkers for assisting early diagnosis of DM with cardio-renal-liver- specific metabolic disorders, as well as for the development of miRNA-targeting agents.