Early diabetic neuropathy:Triggers and mechanisms  

作　　者：Maxim Dobretsov Dmitry Romanovsky Joseph R Stimers 

机构地区：[1]Departments of Anesthesiology, Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, United States [2]Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, United States [3]Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, United States

出　　处：《World Journal of Gastroenterology》2007年第2期175-191,共17页世界胃肠病学杂志（英文版）

基　　金：Supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases, No. DK067248

摘　　要：Pedpheral neuropathy, and specifically distal peripheral neuropathy （DPN）, is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presenta- tions of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glu- cose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has ac- cumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, cor- relation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our un- derstanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.

关 键 词：glucose tolerance HYPERGLYCEMIA Insulinopenia INSULINRESISTANCE 

分 类 号：R587.2[医药卫生—内分泌]