Multifaceted role of genetic and epigenetic architecture of glucose homeostasis and diabetes

Glucose homeostasis depends on coordinated genetic and epigenetic regulation of pancreatic beta-cells, insulin-sensitive tissues, and neuroendocrine circuits. This review synthesises evidence from over 600 GWAS loci and the primary literature published between 2008 and 2026, and emerging single-cell functional genomics, CRISPR-based perturbation screens, deep-learning variant-effect predictors (DeepSEA, Enformer, AlphaGenome), and polygenic risk frameworks to explain insulin secretion, insulin signalling, and diabetes susceptibility, converting GWAS associations into mechanistic insight and genotype-guided precision therapies.