Illuminating diabetes via multi-omics: Unraveling disease mechanisms and advancing personalized therapy

Diabetes mellitus (DM) comprises distinct subtypes-including type 1 DM, type 2 DM, and gestational DM - all characterized by chronic hyperglycemia and substantial morbidity. Conventional diagnostic and therapeutic strategies often fall short in addressing the complex, multifactorial nature of DM. This review explores how multi-omics integration enhances our mechanistic understanding of DM and informs emerging personalized therapeutic approaches. We consolidated genomic, transcriptomic, proteomic, metabolomic, and microbiomic data from major databases and peer-reviewed publications (2015-2025), with an emphasis on clinical relevance. Multi-omics investigations have identified convergent molecular networks underlying β-cell dysfunction, insulin resistance, and diabetic complications. The combination of metabolomics and microbiomics highlights critical interactions between metabolic intermediates and gut dysbiosis. Novel biomarkers facilitate early detection of DM and its complications, while single-cell multi-omics and machine learning further refine risk stratification. By dissecting DM heterogeneity more precisely, multi-omics integration enables targeted interventions and preventive strategies. Future efforts should focus on data harmonization, ethical considerations, and real-world validation to fully leverage multi-omics in addressing the global DM burden.