Diabetes Mellitus and Infection Susceptibility: An Immunometabolic Interface

Diabetes mellitus (DM) is a rapidly growing global health burden and a major driver of infection-related morbidity and mortality. Chronic hyperglycemia disrupts both innate and adaptive immunity through impaired complement activity, dysfunctional dendritic cells and natural killer cells, altered macrophage polarization and efferocytosis, and neutrophil defects including reduced chemotaxis, impaired phagocytosis, and dysregulated NETosis. These immune abnormalities, compounded by endothelial dysfunction and microvascular disease, increase susceptibility to severe and recurrent infections such as urinary tract infections, tuberculosis, pneumonia, skin and soft tissue infections, and invasive fungal diseases. Emerging evidence also supports a bidirectional relationship in which infections may precipitate or aggravate DM via mechanisms including molecular mimicry, β-cell injury, chronic inflammation, and gut microbiota dysbiosis, contributing to insulin resistance and β-cell dysfunction. Recurrent infections and frequent exposure to broad-spectrum antibiotics, together with altered pharmacokinetics, chronic wounds with biofilm formation, and prolonged healthcare exposure, create strong selective pressure for antimicrobial resistance (AMR) in diabetic populations. Using clinical and scientific based evidence, this review explores mechanisms linking DM, infection risk, and AMR, highlighting implications for the diagnosis, therapy, stewardship, and vaccination, as well as outlines key research gaps including improved AMR surveillances stratified by diabetes status and integrated predictive models incorporating glycemic control, host factors, and microbial genomics.