Structure-function interactions in the therapeutic response of diabetic neuropathy

Abstract

Conventional electrophysiologic measurements such as nerve conduction velocity, compound action potential, and neuropathic symptom scores have been used to assess the severity of diabetic neuropathy and have been the major efficacy end points following pharmacologic intervention trials. Unfortunately, these measurements are not particularly sensitive and their reproducibility is, at best, good. Detailed morphometric analysis of sural nerve biopsies has evolved as a sensitive and highly reproducible method for assessing the severity and progression of diabetic peripheral neuropathy. In this study we demonstrate highly significant correlations between morphometric parameters of diabetic sural nerves and electrophysiologic and sensory score measurements of the same sural nerve. These data suggest that detailed morphometric examination is a more sensitive and reproducible method for assessing the severity of diabetic neuropathy, and that quantitative morphometric parameters provide sensitive indicators of electrophysiologic and clinically meaningful nerve damage. Morphometric analysis of sural nerve biopsies therefore constitutes a rational basis for sensitive efficacy end points in the design of future therapeutic clinical trials.