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 diab...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.展开更多
基金Supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases, No. DK067248
文摘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.
