Diabetes-Associated Hepatotoxicity and Nephrotoxicity: Roles of Oxidative Stress and Immunomodulation in Organ Crosstalk
Diabetes mellitus is a systemic metabolic disorder that accelerates injury to both the liver and kidneys. Beyond hemodynamic and metabolic derangements, two convergent hallmarks-oxidative stress and immune dysregulationshape the trajectory of diabetes-associated hepatotoxicity and nephrotoxicity. Hyperglycemia, insulin resistance, and lipid overload drive mitochondrial and NADPH oxidase–derived reactive oxygen species, advanced glycation endproduct signaling, endoplasmic reticulum stress, and impaired autophagy. These redox disturbances activate innate and adaptive immune programs, including Toll-like receptor pathways, NLRP3 inflammasome assembly, macrophage polarization, and T-cell skewing, thereby sustaining inflammation and fibrotic remodeling. The liver and kidney communicate through cytokines, chemokines, hepatokines, adipokines, bile acid–FXR signaling, extracellular vesicles, and uremic toxins, creating a feed-forward hepato–renal axis that amplifies injury in both organs. This review synthesizes current mechanistic understanding of oxidative and immune pathways in diabetic liver and kidney disease, highlights emerging biomarkers and noninvasive assessment tools, and outlines therapeutic strategies-metabolic, antioxidant, and immunomodulatory for interrupting shared nodes of pathobiology and organ crosstalk.