MEDICAL BASIS OF DIABETIC NEUROPATHY FORMATION (REVIEW).

Nowadays, chronic diseases are leading cause of death worldwide. One of popular chronic disease of 21 century is Diabetes Mellitus (DM) that affected 422 million people around the world in 2014; its prevalence is expected to increase to 592 million by the year 2035. Diabetic neuropathy (DN) seems to be the most common and least understood complication being present in over 50% of chronic diabetics. As the latest date explain the pathogenesis of DN is not fully understood. Therefore, considering the widespread of DN, severity of its consequences, it is vital to investigate details of its pathophysiology and find therapeutic strategies to improve patients' condition. Generally two mechanisms have been suggested to be involved in the pathogenesis of diabetic neuropathy. The first mechanism is the activation of the Renin Angiotensin Aldosterone System (RAAS) in the presence of hyperglycemia with increased tissue level of Angiotenzin II (Ang II). Ang II stimulates Nicotin Adenine Dinucleotide (Phosphate) (NAD (P)) oxidase which enhances oxidative stress and vascular damage and leading to DN. The other mechanism is linked with disturbance in the metabolism and vasculature of nerve tissue in the presence of excessive uptake of glucose. Conclusion: In our review we have discussed different mechanisms involved in formation of DM and DN. Based on the latest research studies the main component in the big picture of DN formation is hyperglycemia.The list of mechanisms are associated with high glucose level leading inflammation, oxidative stress, hypoxia and apoptosis through the activation of several pathogenic pathways induced by Tumor Necrosis Factor alfa (TNFa), AgII, (pro)renin, Protein Kinase C (PKC), glycolysis intermediated products, Cyclooxygenase 2 (COX2) and reactive nitrogen species (RNS). Therefore to use drugs linked with above discussed pathological processes would be effective solution in the treatment of DM and its complications.