This work addresses several unresolved questions in the field: (1) whether the STZ-HFD model better reflects the inflammatory complexity of T2D in the IVD compared to leptin-deficient models; (2) how systemic metabolic stress translates into local disc pathology at molecular and biomechanical levels; and (3) whether chronic hyperglycemia alters DAMP-RAGE (also known as AGER) interactions and downstream inflammatory signaling in a disc-specific manner. The gene discussed is AGER; the disease is type 2 diabetes mellitus.