title: Pathological mechanisms involved in diabetic neuropathy: can we slow the process?
abstract: Diabetic polyneuropathy (DPN) is the most common late diabetic complication, and is more frequent and severe in the type 1 diabetic population. Currently, no effective therapy exists to prevent or treat this complication. Hyperglycemia remains a major therapeutic target when dealing with DPN in both type 1 and type 2 diabetes, and should be supplemented by aldose reductase inhibition and antioxidant treatment. However, in the past few years, preclinical and clinical data have indicated that factors other than hyperglycemia contribute to DPN, and these factors account for the disproportionality of prevalence of DPN between the two types of diabetes. Insulin and C-peptide deficiencies have emerged as important pathogenetic factors and underlie the acute metabolic abnormalities, as well as serious chronic perturbations of gene regulatory mechanisms, impaired neurotrophism, protein-protein interactions and specific degenerative disorders that characterize type 1 DPN. It has become apparent that in insulin-deficient conditions, such as type 1 diabetes and advanced type 2 diabetes, both insulin and C-peptide must be replaced in order to gain hyperglycemic control and to combat complications. As with any chronic ailment, emphasis should be on the prevention of DPN; as the disease progresses, metabolic interventions, be they directed against hyperglycemia and its consequences or against insulin/ C-peptide deficiencies, are likely to be increasingly ineffective.
authors.affiliation: Wayne State University, Department of Pathology, 540 East Canfield Avenue, Detroit, MI 48201, USA. asima@med.wayne.edu
authors.forename: Anders A F
authors.initials: AA
authors.lastname: Sima
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002096:C-Peptide / Q000172:deficiency; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D050356:Lipid Metabolism; D009410:Nerve Degeneration; D020932:Nerve Growth Factor / Q000627:therapeutic use; D018384:Oxidative Stress; D011108:Polymers / Q000378:metabolism
chemical_list: D002096:C-Peptide; D011108:Polymers; C024617:polyol; D020932:Nerve Growth Factor; D000449:Aldehyde Reductase