INS and diabetes mellitus: Additionally, it disrupts chondrocyte metabolism, evidenced by increased IL-6 and PGE2 production and reduced autophagy and heme oxygenase expression under IL1-beta stimulation in diabetic cartilage, signaling the suppression of critical antioxidant pathways.[30–32] Insulin resistance exacerbates joint tissue damage, stemming from both localized diabetic synovial membrane resistance[33] and systemic low-grade inflammation.[34] Notably, the synovium in obese OA and DM patients shows marked insulin resistance,[35] diminishing insulin’s capacity to mitigate synovial inflammation and catabolism.