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Figure 1. Evidence-based classification of EV-associated and EV-independent miRNA mechanisms in diabetic cardiomyopathy. Diabetic metabolic stress, including hyperglycemia, insulin resistance, lipotoxicity, and chronic inflammation, alters intercellular communication and miRNA-associated signaling in the diabetic heart. I, directly supported EV cargoes: miR-320 is transferred from diabetic cardiomyocytes to endothelial cells through EVs, where it suppresses IGF-1, HSP20, and ETS2 and impairs endothelial proliferation, migration, and tube formation. II, EV-associated signals with context-limited evidence: circulating miR-16-2-3p has been associated with diabetic coronary microvascular dysfunction, whereas dendritic-cell-derived miR-494-3p promotes angiogenesis in a myocardial infarction model; these findings should not be directly extrapolated to DCM. III, DCM-associated miRNA pathways without confirmed EV involvement: miR-34a, miR-200b/c, miR-195, and miR-451 contribute to vascular, fibrotic, hypertrophic, or metabolic abnormalities in diabetic or related cardiac models, but direct EV loading or EV-mediated transfer has not been established. The lower panel summarizes cellular processes potentially affected by EV-mediated communication and their contribution to diabetic cardiac remodeling and dysfunction. This evidence-based classification distinguishes experimentally supported EV cargoes from EV-associated signals and miRNA mechanisms for which direct EV involvement remains unconfirmed. ↑ Indicate upregulated; ↓ indicate downregulated; Solid arrows indicate established direct interactions, whereas dashed arrows denote putative or indirect regulatory relationships that require further experimental validation; T-bars represent inhibition. ACADM: Acyl-CoA dehydrogenase medium chain; AMPK: AMP-activated protein kinase; DCM: diabetic cardiomyopathy; DM: diabetes mellitus; EVs: extracellular vesicles; ETS2: ETS proto-oncogene 2; HG: hyperglycemia; HSP20: heat shock protein 20; IGF-1: insulin-like growth factor 1; LKB1: liver kinase B1; miRNA: microRNA; NO: nitric oxide; PK: pyruvate kinase; SIRT1: sirtuin 1; T2DM: type 2 diabetes mellitus; TGF-β: transforming growth factor beta.