Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.

Diabetes mellitus is a chronic metabolic disease that has become a global health concern, leading to complications such as retinopathy, nephropathy, vasculopathy, and delayed wound healing. Neutrophils, as essential immune cells, protect the host by releasing neutrophil extracellular traps (NETs)-web-like structures composed of DNA and antimicrobial proteins that trap and kill pathogens. However, in diabetes, persistent hyperglycemia and inflammation induce excessive NET formation, resulting in endothelial damage, thrombosis, and tissue injury, which aggravate disease progression. Recent studies show that NETs not only participate in pathogen defense but also amplify chronic inflammation and vascular dysfunction in diabetic complications. This review highlights the dual role of neutrophils and NETs in diabetes, elucidates their molecular mechanisms in inflammation and vascular injury, and summarizes emerging therapeutic strategies targeting NETs-such as DNase I, PAD4 inhibitors, and IL-8 blockade-offering new insights for the prevention and treatment of diabetes and its complications.