In summary, the following key findings support an AGE-activated MD2-TLR4 pathogenic mechanism as a central driving force behind inflammatory myocardial injury in diabetes: (1) HG was associated with elevated AGE and AGE-MD2 complexes in serum and myocardial tissue; (2) diabetic human subjects and mice showed upregulated MD2 and TLR4 levels; (3) AGE products bound directly to MD2 and activated MD2-TLR4 signaling; (4) MD2 knockout or pharmacological inhibition effectively blocked diabetes-induced NF-κB/MAPK activation along with upregulation of inflammatory factors. This evidence concerns the gene LY96 and diabetes mellitus.