S118 Mechanisms of diabetic neuropathy

Abstract

Objectives Diabetic polyneuropathy (DPN) is the most common peripheral neuropathy representing a severe disabling condition. There is currently no disease modifying treatment, and development of targeted therapies depends on understanding the complex underlying mechanisms of DPN. The objective of this review is to discuss mechanisms of DPN. Methods DPN is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these as the cause of DPN have been controversial. The scientific community has been divided into two groups, favoring either metabolic or neurovascular mechanisms. Results Since DPN is decreased by improved metabolic control, hyperglycemia is assumed to be the main cause. Long lasting hyperglycemia leads to a downstream metabolic cascade which affects mitochondrial function and causes an excess formation of reactive oxygen species and exaggerated oxidative stress. Additionally, dyslipidemia, insulin resistance, autoimmunity, and epigenetics are suggested to contribute to metabolic mechanisms of DPN. The idea that microvascular changes cause DPN was challenged in early studies. There is, however, increasing evidence that changes in endoneurial capillary morphology and vascular reactivity may predate the development of DPN. In recent studies, disturbances in capillary function were shown to reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. Discussion The ability to show immediately the effects on patient axons of interventions such as ischemia makes excitability testing a powerful method to investigate disease pathophysiology. Significance Axonal excitability tests may contribute to understanding the mechanisms of diabetic neuropathy with the possibility to provide information about the activity of different ion channels and the electrogenic sodium pump.