Polyphenol-Mediated Modulation of Oxidative Stress Pathways in Type 1 Diabetes: A Systematic Review

Oxidative stress is a central component of type 1 diabetes (T1D) pathophysiology, contributing to pancreatic β-cell vulnerability and the development of chronic complications. Current therapeutic strategies are primarily focused on glycemic control and do not directly address underlying redox imbalance. Dietary polyphenols, a structurally diverse class of plant-derived compounds, have been investigated for their antioxidant and cytoprotective properties, yet their role in T1D has not been systematically defined. This systematic review evaluates the effects of polyphenols on oxidative stress and glycemic parameters in preclinical models of T1D. Across studies, polyphenols were consistently associated with attenuation of oxidative stress, as evidenced by reductions in lipid peroxidation and reactive oxygen and nitrogen species, along with restoration of endogenous antioxidant defenses, including superoxide dismutase, catalase, and glutathione. These effects were frequently linked to modulation of redox-sensitive signaling pathways, particularly Nrf2-dependent mechanisms. In contrast, glycemic outcomes were heterogeneous and influenced by compound-specific and experimental factors. Modulation of oxidative stress markers was often observed independently of changes in glycemic parameters, suggesting a primary redox-mediated mode of action. These findings provide a mechanistic rationale for prioritizing oxidative-stress-focused endpoints in future translational studies and support the evaluation of polyphenols as adjunctive strategies targeting redox imbalance in T1D.