Abstract:Diabetes mellitus, encompassing type 1 (T1D) and type 2 diabetes (T2D), is a multifactorial metabolic disorder affecting millions globally, characterized by chronic hyperglycemia stemming from insulin deficiency and/or resistance. While genetic predisposition has been extensively studied, emerging evidence implicates epigenetic programming as a critical regulator that integrates environmental and developmental signals with genomic information to modulate diabetes susceptibility, onset, and progression. Epigenetic modifications—such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation—alter gene expression without changing the DNA sequence and are dynamic across cell types and developmental stages. In T1D, epigenetic dysregulation promotes autoimmune T cell activation and β-cell fragility, while in T2D, these changes mediate insulin resistance, β-cell dysfunction, and metabolic memory. Environmental factors, including in utero exposures, diet, physical activity, stress, and toxicants, profoundly impact epigenetic landscapes, influencing diabetes risk across the lifespan. Additionally, epigenetic biomarkers derived from peripheral tissues offer promising avenues for early diagnosis and prognosis. The advent of epigenetic therapies, including inhibitors targeting DNA methyltransferases and histone deacetylases, combined with nutritional and lifestyle interventions, provides novel opportunities for precision medicine. This review systematically synthesizes current knowledge on epigenetic mechanisms in diabetes, the influence of environmental and developmental factors, biomarker potential, and emerging therapeutic strategies, highlighting future directions for epigenome-based interventions to alleviate the global diabetes burden.