Genetic and epigenetic contributions to the pathogenesis of type 1 and type 2 diabetes

Abstract

This thesis explores the genetic and epigenetic contributions to the pathogenesis of Type 1 and Type 2 diabetes mellitus, two of the most prevalent global metabolic disorders. It highlights the etiological distinctions between autoimmune beta‑cell destruction in Type 1 diabetes and insulin resistance with beta‑cell dysfunction in Type 2 diabetes. The work synthesizes evidence on HLA class I and II loci, insulin gene polymorphisms, and non‑MHC variants that predispose individuals to Type 1 diabetes. It further examines epigenetic mechanisms, DNA methylation, histone modification, and non‑coding RNAs that modulate gene expression and immune tolerance. Clinical manifestations, risk factors, and systemic complications are contextualized within the global epidemiological burden of diabetes. The thesis underscores the interplay of genetic susceptibility and environmental triggers, shaping disease onset, progression, and heterogeneity. Tables and figures provide structured clarity on symptoms, genetic loci, and pathogenic cascades, enhancing comprehension for clinical and research audiences. By integrating molecular insights with epidemiological data, the study emphasizes the need for precision medicine in diabetes management. It contributes to academic discourse by bridging basic science and translational relevance, offering a framework for future therapeutic strategies. Overall, the thesis demonstrates scholarly rigor, strong synthesis of literature, and clear articulation of diabetes as a multifactorial disorder requiring multidisciplinary intervention