The Interplay of Insulin Resistance, Inflammation, and Antioxidant Depletion in Diabetes: A Comprehensive Review

Chelimo Faith Rebecca

Department of Clinical Medicine and Dentistry Kampala International University Uganda

Email: rebecca.chelimo@studwc.kiu.ac.ug

ABSTRACT

Diabetes mellitus arises through a multifaceted network of metabolic derangements, prominently featuring insulin resistance, chronic inflammation, and oxidative stress. These three processes do not occur in isolation; rather, they form a self-reinforcing triad that accelerates metabolic dysfunction and tissue injury. Insulin resistance increases glucose and lipid flux into susceptible tissues, driving mitochondrial overload and excessive generation of reactive oxygen species (ROS). Concurrently, hyperglycaemia and dyslipidaemia activate innate immune sensors, promoting the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. These inflammatory mediators further impair insulin receptor signaling, creating a vicious cycle that sustains metabolic impairment. At the same time, antioxidant defenses—including glutathione, superoxide dismutase, catalase, and peroxiredoxins—become depleted due to chronic oxidative burden and reduced transcriptional activation of protective pathways such as Nrf2. The resulting imbalance intensifies ROS-mediated cellular injury, endothelial dysfunction, β-cell exhaustion, and immunometabolic dysregulation. This review synthesizes current mechanistic insights into the interconnected roles of insulin resistance, inflammation, and antioxidant depletion in type 1 and type 2 diabetes, with emphasis on molecular pathways, clinical implications, and emerging therapeutic targets. Understanding these intertwined processes is essential for designing integrated interventions aimed at preventing disease progression and reducing complications.

Keywords: insulin resistance, inflammation, oxidative stress, antioxidant depletion, diabetes mellitus

CITE AS: Chelimo Faith Rebecca (2026). The Interplay of Insulin Resistance, Inflammation, and Antioxidant Depletion in Diabetes: A Comprehensive Review. IAA Journal of Applied Sciences 14(1):30-35. https://doi.org/10.59298/IAAJAS/2026/1413035