These mechanism most prominent includes altered insulin signaling, deposition of advanced nonenzymatic glycation end products (AGE) into the ECM [32], increased myocardial collagen deposition with down- regulation of matrix metalloproteinases (MMPs) and upregulation of tissue inhibitors of metalloproteinases (TIMPs) [33], and substrate shifts from glucose to free fatty acids [34] as well as endothelial dysfunction [35]. Here, INS is linked to endothelial dysfunction.