As the key mediator of vascular injury in patients with DM, methylglyoxal, the precursor of AGEs, significantly activates autophagy and inhibits angiogenesis by inhibiting ROS-mediated AKT/mTOR signaling pathways or inhibits phosphorylation of sestrin 1 (SESN1) and SESN2 and mTORC1 activation by activating p53 to promote autophagy activation and induce EC activity decline and injury (86, 87). This evidence concerns the gene SESN1 and diabetes mellitus.