Abstract

Hyperglycaemia is a defining biochemical hallmark of diabetes mellitus and exerts profound effects on cellular 
redox homeostasis and immune function. Sustained elevations in blood glucose promote excessive generation of 
reactive oxygen species (ROS) through multiple mechanisms, including mitochondrial electron transport chain 
overload, activation of NADPH oxidases, advanced glycation end-product (AGE) formation, polyol pathway flux, 
and impaired antioxidant defenses. The resulting oxidative environment disrupts cellular signaling, damages 
biomolecules, and alters transcriptional programs essential for innate and adaptive immunity. Immune dysfunction 
under chronic hyperglycaemia involves impaired neutrophil chemotaxis and phagocytosis, dysfunctional 
macrophage polarization, aberrant antigen presentation, T-cell exhaustion, dysregulated cytokine production, and 
heightened susceptibility to infections. Moreover, immune dysregulation contributes to the chronic low-grade 
inflammation and tissue damage characteristic of diabetes complications, including atherosclerosis, nephropathy, 
neuropathy, and impaired wound healing. This review synthesizes current mechanistic insights into 
hyperglycaemia-induced ROS production and immune impairment, integrating evidence from molecular biology, 
clinical studies, and translational research. We also discuss therapeutic strategies targeting redox imbalance and 
immunometabolic pathways, highlighting emerging antioxidant, metabolic, and immunomodulatory interventions. 
By clarifying the interconnected roles of oxidative stress and immune dysfunction, this review underscores the 
importance of integrated metabolic-immune approaches in the prevention and management of diabetes and its 
complications.