Conversely, the resulting hyperglycemia and dyslipidemia further exacerbate OS through four key mechanisms: (1) the polyol pathway, where glucose conversion to sorbitol depletes NADPH and glutathione; (2) AGE-RAGE interactions that activate pro-inflammatory cascades and additional ROS generation; (3) protein kinase C (PKC) activation, which upregulates NOX isoforms; and (4) lipid peroxidation, where free fatty acids (FFAs) overload mitochondrial β-oxidation, generating cytotoxic aldehydes like 4-hydroxynonenal (4-HNE) (Młynarska et al., 2024). Here, PRRT2 is linked to Hyperglycemia.