Hyperglycaemia-Induced ROS and Immune Dysfunction: A Comprehensive Review

Tom Robert

Department of Clinical Medicine and Dentistry, Kampala International University Uganda

Email: robert.tom@studwc.kiu.ac.ug

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.

Keywords: hyperglycaemia, reactive oxygen species, immune dysfunction, oxidative stress, diabetes complications

CITE AS: Tom Robert (2026). Hyperglycaemia-Induced ROS and Immune Dysfunction: A Comprehensive Review. IAA Journal of Applied Sciences 14(1):24-29. https://doi.org/10.59298/IAAJAS/2026/1412429