Regulation of m6A methylation in the immune microenvironment in the development of diabetes mellitus.

Diabetes mellitus is a widespread metabolic disorder characterized by chronic hyperglycemia, driven primarily by insulin resistance and β-cell dysfunction. N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotes, has emerged as a critical regulator in diabetes pathogenesis. This review outlines how m6A methylation, mediated by writers (METTL3, METTL14), erasers (FTO, ALKBH5), and readers (YTHDFs, IGF2BPs), influences key diabetic processes including β-cell function, lipid metabolism, and insulin resistance. A key focus is on the role of m6A in modulating the immune microenvironment, such as by regulating macrophage polarization and T-cell activity, which contributes to inflammation and disease progression in both type 1 and type 2 diabetes. Furthermore, m6A dysregulation is implicated in multiple diabetic complications. Therapeutic agents, including existing drugs, natural extracts, and specific m6A inhibitors, can modulate m6A levels, highlighting its potential as a therapeutic target. This review synthesizes the evidence linking m6A to diabetes, with an emphasis on immunoregulation, and suggests that targeting m6A pathways offers promise for future treatments.