Exosomal miRNAs demonstrated strong diagnostic performance for diabetic nephropathy (pooled AUC=0.79) and ischemic heart disease (miR-155-5p AUC=0.901) in patients with type 2 diabetes.
Do extracellular vesicle-derived microRNAs serve as accurate diagnostic biomarkers for diabetic nephropathy and cardiovascular diseases in patients with type 2 diabetes?
Extracellular vesicle-derived microRNAs show strong potential as non-invasive diagnostic biomarkers for diabetic nephropathy and cardiovascular complications in type 2 diabetes, though standardization and large-scale validation are needed.
Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 152 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications.
Arailym et al. (2026) studied this question. Exosomal miRNAs demonstrated strong diagnostic performance for diabetic nephropathy (pooled AUC=0.79) and ischemic heart disease (miR-155-5p AUC=0.901) in patients with type 2 diabetes.