A significant association between endothelial NO synthase (eNOS) gene polymorphisms and type 2 diabetes, as well as decreased eNOS expression in skeletal muscle, and reduced NO production and bioavailability in insulin resistance states, clearly underlines the role of NO and its metabolites in the development of hyper-insulinemia, insulin resistance, and type 2 diabetes [25–28]. This evidence concerns the gene NOS3 and type 2 diabetes mellitus.