A brief review on the pathogenesis of human diabetic neuropathy: Observations and postulations

Diabetic neuropathy (DN), an important microvascular complication of diabetes, is one of the major causes of morbidity in patients with diabetes. Studies have confirmed that glycaemic control and duration of diabetes are important factors for the development of DN. However, the exact mechanism of damage to peripheral nerves due to prolonged hyperglycaemic exposure is still not clear. Recent epidemiological studies have highlighted the importance of cardiovascular risk factors such as hypertension, smoking, raised serum cholesterol, triglycerides and lipoprotein a to the development of DN. Various mechanisms of microvascular and haemodynamic dysfunction of capillaries of nerve fibres have been postulated in the development of DN. Similarly endothelial dysfunction due to activation of protein kinase C, oxidative stress, advanced glycation end products and polyol pathway activation has been shown to be related to DN in human and experimental DN. Other possible mechanisms such as platelet dysfunction, essential fatty acid deficiency, immunological mechanisms, nerve growth factor deficiency and presence of adhesion molecules have been described in relation to DN. However, no single theory can explain the exact pathogenic mechanism of the development of DN. This review looks into different theories that have been proposed and describes the inter-relationship of various factors that can lead to the development of DN.