Hyperglycemia-driven AGE-RAGE signaling, PKC activation, and RAAS dysregulation converge on oxidative stress, endothelial dysfunction, and profibrotic transcription (e.g., TGF-beta/Smad), while mitochondrial and endoplasmic-reticulum stress amplify lipotoxicity and cell death. This evidence concerns the gene PRRT2 and endothelial dysfunction.