Peripheral neurogenic lesions in diabetes mellitus

Polyneuropathy is a generalized disorder of the peripheral nervous system. Diabetes mellitus is the main cause of such neuropathies and neuropathy itself is the most frequent complication in diabetic patients. All forms of diabetes are characterized by hyperglycaemia and the development of specific micro-vascular alterations. Blood vessels consistently need neural regulation to maintain their function and nerve cells correspondingly require an appropriate nutrition through capillaries. The diabetic neuropathy probably results both directly from damaging hyperglycaemic effects on neural parenchyma, and indirectly from changes of the neurovascular blood flow with consecutive neuronal ischemia. Persisting hyperglycaemia of the organism is initiating cause and established risk factor for pathological changes and clinical complications in insufficiently treated diabetic patients. In case of hyperglycaemia most cells are able to reduce the transport into the cell. Some cells of retina, kidney and peripheral nerve lack this ability and therefore cannot compensate for ongoing hyperglycaemic states. Since pathological consequences depend on intracellular glucose levels, it seems reasonable that the underlying mechanisms take place inside the cell as well. Increasing flux through the polyol and hexosamine pathway, advanced glycosylation of molecules, activation of protein kinase C and finally oxidative stress seem to be of importance in this context. Those pathways describe toxic effects of the hyperglycemia and pathophysiological consequences on the tissue (oxidants, hyperosmolarity, advanced glycosylation end products), as well as the modification of signalling cascades by products of the glucose metabolism (phospholipids, kinases). Hyperglycaemically induced vascular insufficiency occurs early in diabetic patients, develops simultaneously to progressive neural dysfunction and maintains the severe structural, functional and clinical changes of the disease.