What is the role of hyperglycemia in the pathophysiology of diabetic neuropathy?

Updated: Jan 08, 2019
  • Author: Dianna Quan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

Hyperglycemia causes increased levels of intracellular glucose in nerves, leading to saturation of the normal glycolytic pathway. Extra glucose is shunted into the polyol pathway and converted to sorbitol and fructose by the enzymes aldose reductase and sorbitol dehydrogenase. [15] Accumulation of sorbitol and fructose lead to reduced nerve myoinositol, decreased membrane Na+/K+ -ATPase activity, impaired axonal transport, and structural breakdown of nerves, causing abnormal action potential propagation. This is the rationale for the use of aldose reductase inhibitors to improve nerve conduction. [16]


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