The role of glycation in the pathogenesis of diabetic polyneuropathy

• Published in: Molecular pathology Vol. 54; no. 6; pp. 400 - 408
• Main Author: King, R H M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.12.2001; BMJ Publishing Group Ltd; British Medical Journal Publishing Group
• Subjects: Animals; Axons - pathology; Basement Membrane - pathology; Blood Vessels - pathology; Calmodulin - metabolism; Collagen Type IV - metabolism; Complications and side effects; Development and progression; Diabetes; diabetes mellitus; Diabetic neuropathies; Diabetic Neuropathies - etiology; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - pathology; Extracellular Matrix - metabolism; Ganglia, Spinal - pathology; GAP-43 Protein - metabolism; Glucose - metabolism; glycation; Humans; Microscopy, Electron; Neurons - pathology; Neurons - ultrastructure; peripheral nerve; Peripheral nerve diseases; Peripheral Nerves - metabolism; Peripheral Nerves - pathology; Radial Nerve - ultrastructure; Review; Schwann Cells - pathology; United Kingdom
• ISSN: 1366-8714; 1472-4154
• DOI: 10.1136/mp.54.6.400

The most common neuropathy associated with diabetes mellitus is a distal sensory polyneuropathy. The relative importance of the direct effects of prolonged glycaemia on nervous tissue compared with indirect damage resulting from changes in blood vessels is not known. Although the importance of glycaemia is confirmed by a study showing that the incidence of neuropathy is greatly reduced by strict glycaemic control, many of the details of the deleterious effects of glycaemia on the peripheral nervous system (PNS) are not understood. These may be the result of direct damage to any of the cells in the PNS or the disruption of neuronal metabolism, axonal transport mechanisms, or repair capabilities; in addition, they may result from the effects of glycation on PNS connective tissue or a combination of some or all of the above mentioned mechanisms. The relative importance of these various mechanisms by which diabetes damages the PNS is a matter of conjecture. Therapeutic approaches targeting a specific mechanism such as those utilising aldose reductase inhibitors, or advanced glycation endproduct inhibitors have met with limited success. Clearly, it is difficult to design a treatment for diabetic neuropathy while its pathogenesis is still poorly understood.