Lifestyle Intervention for Pre-Diabetic Neuropathy

  1. A. Gordon Smith, MD12,
  2. James Russell, MD3,
  3. Eva L. Feldman, MD, PHD3,
  4. Jonathan Goldstein, MD4,
  5. Amanda Peltier, MD3,
  6. Sheldon Smith, BS1,
  7. Jouhaina Hamwi, BS1,
  8. Donald Pollari, BS1,
  9. Billie Bixby, BS1,
  10. James Howard, BS1 and
  11. J. Robinson Singleton, MD1
  1. 1Department of Neurology, University of Utah, Salt Lake City, Utah
  2. 2Department of Pathology, University of Utah, Salt Lake City, Utah
  3. 3Department of Neurology, University of Michigan, Ann Arbor, Michigan
  4. 4Department of Neurology, Yale University, New Haven, Connecticut
  1. Address correspondence and reprint requests to A. Gordon Smith, MD, Associate Professor of Neurology and Pathology, University of Utah School of Medicine, 50 N. Medical Dr. SOM 3R152, Salt Lake City, UT 84132. E-mail: gordon.smith{at}


OBJECTIVE—The 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 METHODS—We 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.

RESULTS—Baseline 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).

CONCLUSIONS—These 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.


  • J.R. is a standing member on the American Diabetes Association Complications Grant Review Panel.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 1, 2006.
    • Received January 27, 2006.
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