Molecular Insights and Pharmacotherapy of Diabetic Neuropathy

Abstract

Background: Diabetes mellitus is a chronic disorder of energy metabolism caused by lack or decrease in the effectiveness of insulin, and is characterised by an abnormally elevated blood glucose concentrations and the development of macrovascular, microvascular and/or neuropathic complications. Diabetic neuropathy (DN) is one of the most debilitating outcomes of diabetes mellitus, and may cause pain, decreased mobility as well as amputation. Diabetes can damage the peripheral nervous system (PNS), through the induction of de-myelination in neurones, precipitated by chronic hyperglycaemia-induced oxidative stress, and causing a condition that involves the upper and lower limbs. Objective: The study discussed the risk factors for insulin resistance and pre-diabetes, type II diabetes mellitus and vascular complications, cellular and molecular basis of DN, physiopathological mechanisms, and the pharmacological treatment of DN. Method: The study examined journal articles and standard textbooks, as it relates to diabetes mellitus and its complications. Search for articles on DN was carried out in the literature. These were identified and reviewed for selection using chemical abstracts service, pubmed, google scholar, crossreference, web of science, pubmed central free article, and scopus. The key words used for search were: diabetic neuropathy; diabetic peripheral neuropathy; peripheral neuropathy; microvascular complications of diabetes mellitus; and neuromuscular complications of diabetes mellitus. Result & Discussion: Two hundred and fifty (250) articles and other works were identified, while ninety-seven (97) articles and non-journal materials were extracted and reviewed, taking into account the criteria for selection. Studies done in the last 4.5 decades were included, while works written on other languages, outside English were excluded. Findings indicate that DN is a complex disorder that affects the peripheral and/or cranial nerves, which is caused by unattended or poorly attended, long-term increase in blood glucose concentrations. It relatively manifests early, affecting a significant proportion of the micro-blood vessels in the middle-aged and elderly diabetic patients. DN causes numbness, loss of sensation, and sometimes pain in the feet, legs, arms or hands. Hyperglycaemia causes the activation and inhibition of several molecular pathways that are crucial for homeostasis in neuronal and neuroglial cells. Conclusion: DN is the commonest complication of diabetes mellitus. It has no known definitive therapy. Treatment is essentially symptomatic with huge economic and psychological burden, hence the rationale for a cost effective and targeted therapies. Achieving euglycaemia using anti-diabetic regimens (i.e., insulin and oral hypoglycaemic agents), foot care, changes in feeding habits and lifestyle modification are critical to holistically address the problem.