The sustained hyperglycemia in type 2 diabetes promotes the damage of the small amyelinic type C-fibers of the autonomic nervous systems via oxidative and nitrosative stress, which generates DNA damage, proinflammatory substances release (such as interleukin-1, tumor necrosis factor alpha, and transforming growth factor beta) and a pro-vasoconstriction profile (high levels of endothelin-1 and vascular endothelial growth factor, and a decrease in endothelial nitric oxide synthase production), which results in neuronal toxicity, histological changes, and glial death [62]. Here, NOS3 is linked to Hyperglycemia.