Ferroptosis in diabetes mellitus and its complications: overview of clinical and preclinical research.

Diabetes mellitus, a metabolic disorder of rising global incidence, imposes substantial health burdens through its systemic complications. Although the treatment strategies based on pathological changes and molecular mechanisms are constantly upgrading, the therapeutic effects, especially for complications, are not satisfactory. Emerging evidence highlights ferroptosis-an iron-dependent cell death pathway-as a critical regulator in diabetic pathophysiology. This review synthesizes clinical data, genetic studies, and therapeutic interventions across experimental models to establish ferroptosis's multifaceted involvement in diabetes progression. Multiorgan analyses (pancreatic islets, heart, kidney, liver, brain, etc.) reveal ferroptosis-mediated pathways connecting localized tissue damage to systemic diabetic pathogenesis. Particularly, ferroptosis intersects with characteristic diabetic mechanisms, including oxidative stress, lipid peroxidation, and mitochondrial dysfunction. Our integrated assessment positions ferroptosis as a converging pathological mechanism in diabetes, proposing its molecular mediators as promising targets for innovative combination therapies. This mechanistic understanding could enable novel approaches for mitigating both metabolic dysregulation and end-organ damage in diabetes management.