Hyperinsulinemia might continuously active the growth factor receptor-bound protein-2 signal pathway inactive the insulin receptor substrate pathway, and increase the level of plasminogen activator inhibitor-1, vascular cell adhesion molecule 1, and endothelin-1, which might induce the vasoconstriction, proliferation, migration of endothelium, promote atherosclerotic plaque formation and instability and increase the risk the adverse CV events [27]. Here, INSR is linked to hyperinsulinism.