Abstract

Diabetes mellitus is a complex and heterogeneous metabolic disorder resulting from the interplay between genetic 
susceptibility and environmental factors. Advances in genetic research have significantly improved understanding 
of the molecular mechanisms underlying diabetes risk, particularly for type 1 diabetes mellitus (T1DM) and type 2 
diabetes mellitus (T2DM). T1DM is primarily an autoimmune condition characterized by immune-mediated 
destruction of pancreatic β-cells, while T2DM is a multifactorial disease driven by insulin resistance and impaired 
insulin secretion. Genome-wide association studies (GWAS) have identified numerous genetic loci associated with 
conditions, highlighting their polygenic nature and revealing pathways involved in β-cell function, insulin 
signaling, immune regulation, and metabolic homeostasis. In addition to polygenic risk, monogenic forms of 
diabetes, such as maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes, demonstrate the 
impact of high-penetrance variants on disease development and therapeutic response. Gene–environment 
interactions, ethnic diversity in genetic risk, and functional genomic insights further refine current models of 
diabetes susceptibility. This review synthesizes evidence on the genetic architecture of diabetes, explores 
translational applications in genetic risk prediction and precision medicine, and addresses ethical, legal, and social 
considerations. Understanding the genetic basis of diabetes offers critical opportunities for early risk identification, 
targeted prevention, and personalized therapeutic strategies aimed at reducing the global burden of diabetes.