Chronic hyperglycemia in type 2 diabetes promotes the accumulation of advanced glycation end products (AGEs) that cross-link with type I and II collagen in joint tissues, increasing extracellular matrix stiffness and reducing tissue toughness, which contributes to cartilage degeneration by altering chondrocyte mechanotransduction and promoting inflammatory signaling pathways.

High blood sugar causes sugar molecules to stick to collagen fibers in joint cartilage, making them stiff and brittle. This stiff matrix pushes on cartilage cells, triggering signals that turn on harmful inflammatory pathways. At the same time, the stuck sugar molecules bind to a receptor on the cartilage cells, which also turns on the same inflammatory pathways. Together, these signals cause the cells to produce enzymes that break down the cartilage and stop them from repairing it, leading to joint damage.