Role of the DNA methyltransferases in diabetes mellitus and Its complications

Diabetes mellitus (DM) and its complications represent a major global health burden, driven by a combination of genetic and environmental factors. Growing evidence indicates that epigenetic modifications, particularly DNA methylation, play a critical role in the pathogenesis of DM and its progression to complications such as diabetic cardiomyopathy, nephropathy, retinopathy, and impaired wound healing. DNA methyltransferases (DNMTs), including DNMT1, DNMT3A, and DNMT3B, are key enzymes responsible for establishing and maintaining DNA methylation patterns. Under diabetic conditions, hyperglycemia and metabolic dysregulation lead to aberrant expression and activity of DNMTs, resulting in methylation dysregulation of genes involved in insulin signalling, pancreatic islet β-cell function, oxidative stress, inflammation, and fibrosis. Although numerous studies have identified abnormal DNMT expression in diabetes and its complications, the precise mechanisms triggering DNMT dysregulation and its tissue-specific effects remain incompletely elucidated. This review summarises current advances in understanding the role of DNMTs in the pathogenesis of DM and its complications, discusses their therapeutic potential, and suggests that targeting DNMT-mediated epigenetic pathways may offer novel strategies for preventing and reversing diabetes and its associated complications.