• A Gordon Smith, James Russell, Eva L Feldman, Jonathan Goldstein, Amanda Peltier, Sheldon Smith, Jouhaina Hamwi, Donald Pollari, Billie Bixby, James Howard, and J Robinson Singleton.
• Department of Neurology, University of Utah School of Medicine, 50 N. Medical Drive, SOM 3R152, Salt Lake City, UT 84132, USA. gordon.smith@hsc.utah.edu
• Diabetes Care. 2006 Jun 1; 29 (6): 1294-9.

ObjectiveThe purpose of this study was to evaluate intraepidermal nerve fiber density (IENFD) as a sensitive measure of neuropathy change in patients with neuropathy associated with impaired glucose tolerance (IGT) receiving lifestyle intervention based on that used in the Diabetes Prevention Program.Research Design And MethodsWe performed 3-mm skin biopsies with measurement of IENFD at the distal leg and proximal thigh at baseline and after 1 year in 32 subjects with IGT. Each received individualized diet and exercise counseling as a standard of care. Nerve conduction studies, quantitative sensory testing, quantitative sudomotor axon reflex testing, and the Michigan Diabetic Neuropathy score were performed, and a visual analog pain scale was completed. Two-hour oral glucose tolerance tests (OGTTs) following the American Diabetes Association guidelines were performed, and serum lipid levels were measured at baseline and 1 year later.ResultsBaseline distal IENFD was 0.9 +/- 1.2 fibers/mm and proximal IENFD was 4.8 +/- 2.3 fibers/mm. Baseline distal IENFD correlated with fasting glucose (P < 0.001) and OGTT (P < 0.01). After 1 year of treatment, there was a 0.3 +/- 1.1-fiber/mm improvement in distal IENFD and a 1.4 +/- 2.3-fiber/mm improvement in proximal IENFD (P < 0.004). The change in proximal IENFD correlated with decreased neuropathic pain (P < 0.05) and a change in sural sensory amplitude (P < 0.03).ConclusionsThese findings indicate that diet and exercise counseling for IGT results in cutaneous reinnervation and improved pain. Skin biopsy was the most sensitive measure of neuropathy change over 1 year. IENFD should be included as an end point in future neuropathy trials.

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