Among several options, we have highlighted new promising therapeutic coadjuvants, including the cultured probiotic microorganisms (such as kefir grains) and the PDE5 inhibitors (such as sildenafil), which besides the reduction of hyperglycemia and ameliorate insulin resistance, they have been shown to reduce the oxidative stress and improved the endothelial dysfunction in the systemic vascular circulation. This evidence concerns the gene PDE5A and endothelial dysfunction.