Diabetic neuropathy – a continuing enigma

Abstract

In this article we will review the clinical signs and symptoms of diabetic somatic polyneuropathy (DPN), its prevalence and clinical management. Staging and classi®cation of DPN will be exempli®ed by various staging paradigms of varied sophistication. The results of therapeutic clinical trials will be summarized. The pathogenesis of diabetic neuropathy reviews an extremely complex issue that is still not fully understood. Various recent advances in the understanding of the disease will be discussed, particularly with respect to the differences between neuropathy in the two major types of diabetes. The neuropathology and natural history of diabetic neuropathy will be discussed pointing out the heterogeneities of the disease. Finally, the various prospective therapeutic avenues will be dealt with and discussed.

Intra-axonal recording from large sensory myelinated axons: Demonstration of impaired membrane conductances in early experimental diabetes

“…The axon calibre is the most sensitive parameter affecting conduction velocity [38]. In chronic diabetes nerve conduction slowdown has been associated with neuroanatomical abnormalities [6,39]. This is unlikely to be relevant for early diabetes, as recently shown in the diabetic rat [40].…”

“…These hypotheses deal with several major areas, such as metabolic, ischaemia and oxidative stress, non-specific glycosylation, and disturbances in trophic factors [1,2,3,4]. The histopathological findings of advanced diabetic neuropathy (DN) are characterized by axonal degeneration, demyelination and atrophy that are associated with highly diverse disturbances of peripheral nerve function [2,5,6]. Different positive and negative neurological signs associated with DN suggest modification in axonal membrane excitability.…”

Effect of Treating Streptozotocin‐Induced Diabetic Rats With Sorbinil, Myo‐Inositol or Aminoguanidine on Endoneurial Blood Flow, Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

“…This led to speculation 15 years ago that a common mechanism might induce the diverse complications of diabetes [22]. However, more recent studies have indicated that diabetic neuropathy is likely due to multiple mechanisms involving hyperglycemia and decreased insulin and C-peptide levels that effect both nerve and vascular tissue [17].…”

“…This has led to wide speculation regarding the potential benefit of aldose reductase inhibitor treatment of diabetic complications [10][11][12][13][14][15][16]. However, clinical trials using aldose reductase inhibitors for treatment of diabetic neuropathy have been disappointing [17]. Treatment of diabetic rats with dietary myo-inositol has also been shown to improve nerve function [18][19][20][21].…”

“…This led to speculation 15 years ago that a common mechanism might induce the diverse complications of diabetes [22]. However, more recent studies have indicated that diabetic neuropathy is likely due to multiple mechanisms involving hyperglycemia and decreased insulin and C-peptide levels that effect both nerve and vascular tissue [17].Another mechanism thought to contribute to diabetic complications is non-enzymatic glycation of proteins. Treatment of diabetic rats with aminoguanidine, an inhibitor of the formation of advanced glycosylation end products [23], ameliorates the slowing of motor nerve conduction velocity and reduction of endoneurial blood flow [24][25][26][27][28].…”