{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:05:41Z","timestamp":1784174741786,"version":"3.55.0"},"reference-count":141,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes is increasingly recognized as a systemic disorder driven not only by chronic hyperglycemia and insulin resistance, but also by dysregulated interorgan communication. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as biologically active carriers of proteins, lipids, and microRNAs capable of modulating gene expression in recipient cells. This narrative review integrates clinical, experimental, and translational evidence on EV-associated microRNAs as candidate biomarkers and potential mediators of diabetic complications, with emphasis on diabetic neuropathy, diabetic kidney disease, diabetic retinopathy, and metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This review was aligned with the SANRA framework and focused on biological plausibility, evidence from tissue and biofluids, biomarker potential, therapeutic implications, and barriers to clinical translation. Studies were additionally interpreted according to biological matrix, EV-carrier specificity, analytical platform, study design, and level of functional validation. Results: Across complications, EV-associated microRNAs appear to participate in shared pathogenic processes, including oxidative stress, inflammation, endothelial dysfunction, fibrosis, angiogenesis, neurodegeneration, and metabolic memory. In diabetic neuropathy, microRNAs such as miR-146a, miR-155, miR-21-5p, and miR-148a-3p have been linked to neuroinflammation, Schwann-cell dysfunction, axonal injury, and neuropathic pain. In diabetic kidney disease, miR-21, miR-29, miR-30, and miR-126 are implicated in podocyte injury, tubulointerstitial fibrosis, albuminuria, and microvascular dysfunction. In diabetic retinopathy, microRNAs including miR-146a, miR-155, miR-21, miR-126, and miR-200b contribute to neurovascular injury, inflammation, barrier disruption, and angiogenesis. In MASLD associated with diabetes, hepatocyte-derived EVs carrying microRNAs such as miR-1 and miR-126a-3p may link hepatic lipotoxicity to endothelial inflammatory and \u03b2-cell dysfunction. Conclusions: Although EV-associated microRNAs offer promising opportunities for biomarker discovery, risk stratification, and targeted therapies, clinical translation remains limited by heterogeneity in EV isolation, microRNA quantification, biological matrices, and outcome definitions. Distinguishing EV-associated miRNAs from total circulating extracellular miRNAs remains essential for biological interpretation. Standardized, longitudinal, and externally validated studies are required before these signals can be implemented as actionable tools in precision diabetes care.<\/jats:p>","DOI":"10.3390\/metabo16070500","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:34:23Z","timestamp":1784172863000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicle-Associated microRNAs as Candidate Biomarkers and Mediators of Diabetic Complications: Clinical and Translational Evidence Across Neuropathy, Diabetic Kidney Disease, Retinopathy, and MASLD"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-6060","authenticated-orcid":false,"given":"Ra\u00fal","family":"Ibarra-Salce","sequence":"first","affiliation":[{"name":"Facultad de Medicina Unidad Saltillo, Universidad Aut\u00f3noma de Coahuila, Saltillo 25160, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1790-4408","authenticated-orcid":false,"given":"Jos\u00e9 Luis Eduardo","family":"Doval-Caballero","sequence":"additional","affiliation":[{"name":"Cl\u00ednica de Obesidad, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n \u201cSalvador Zubir\u00e1n\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Uribe-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Hospital \u00c1ngeles Clinica Londres, Mexico City 06700, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genesis Dinora","family":"Eugenio-Ponce","sequence":"additional","affiliation":[{"name":"Hospital San Angel Inn Satelite, Naucalpan de Ju\u00e1rez 53100,  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3790-680X","authenticated-orcid":false,"given":"Mariela","family":"Ibarra-Salce","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Hospital General de Zona N. 2, Saltillo 25240,  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Jaime-Leal","sequence":"additional","affiliation":[{"name":"Intus Digestiva, Hospital \u00c1ngeles Torre\u00f3n, Torre\u00f3n 27250,  Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-0383","authenticated-orcid":false,"given":"Manuel Ram\u00f3n","family":"Garc\u00eda-S\u00e1enz","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital de Especialidades \u201cDr. Bernardo Sep\u00falveda\u201d Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida Cuauht\u00e9moc 330, Col. Doctores, Del. Cuauht\u00e9moc, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.2337\/dbi18-0021","article-title":"Exosomes or Microvesicles, a Secreted Subcellular Organelle Contributing to Inflammation and Diabetes","volume":"67","author":"Dai","year":"2018","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/cvr\/cvac031","article-title":"Methods for the identification and characterization of extracellular vesicles in cardiovascular studies: From exosomes to microvesicles","volume":"119","author":"Davidson","year":"2023","journal-title":"Cardiovasc. 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