These factors contribute to DKD progression through two key mechanisms: first, adipokine dysregulation (e.g., elevated leptin, reduced adiponectin) impairs insulin signaling and induces insulin resistance in renal tubular epithelial cells; second, pro-inflammatory cytokines and toxic lipid metabolites directly damage renal parenchymal cells (podocytes, tubular epithelial cells) and activate the TGF-β1/Smad pathway, promoting renal interstitial fibrosis (90, 100). Here, INS is linked to diabetic kidney disease.