Abstract

Diabetes mellitus is a global metabolic disorder characterized by chronic hyperglycaemia and an array of 
microvascular and macrovascular complications. A substantial body of evidence implicates oxidative stress-an 
imbalance between reactive oxygen species (ROS) production and antioxidant defenses a central mechanism in the 
initiation and progression of diabetic pathology. Hyperglycaemia potentiates ROS generation through multiple 
biochemical pathways, including increased mitochondrial electron transport chain leakage, activation of the polyol 
pathway, advanced glycation end-product (AGE) formation, protein kinase C (PKC) activation, and enhanced 
hexosamine flux. These ROS-driven processes damage cellular macromolecules, impair signalling, and trigger 
inflammatory cascades that contribute to β-cell dysfunction, insulin resistance, endothelial injury, neuropathy, 
nephropathy, and hepatopathy. Endogenous antioxidant systems (enzymatic: superoxide dismutase, catalase, 
glutathione peroxidase; non-enzymatic: glutathione, vitamins C and E, and thiol-containing proteins) attempt to 
neutralize oxidative insults, but are often overwhelmed in diabetes. Therapeutic strategies aiming to rebalance redox 
homeostasis-ranging from lifestyle modifications and glycaemic control to pharmacological antioxidants and agents 
that upregulate endogenous defenses-show promise in ameliorating diabetic complications. This review synthesizes 
mechanistic links between oxidative stress and diabetic pathophysiology, discusses biomarkers and experimental 
models used to study redox imbalance, evaluates antioxidant-based interventions, and highlights gaps and future 
directions for translating redox biology into clinical practice.