title: Lifestyle intervention for pre-diabetic neuropathy.
abstract: 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.
  
  
  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.
authors.affiliation: 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
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Smith
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldstein
authors.forename: Amanda
authors.initials: A
authors.lastname: Peltier
authors.forename: Sheldon
authors.initials: S
authors.lastname: Smith
authors.forename: Jouhaina
authors.initials: J
authors.lastname: Hamwi
authors.forename: Donald
authors.initials: D
authors.lastname: Pollari
authors.forename: Billie
authors.initials: B
authors.lastname: Bixby
authors.forename: James
authors.initials: J
authors.lastname: Howard
authors.forename: J Robinson
authors.initials: JR
authors.lastname: Singleton
mesh_terms: D000368:Aged; D001706:Biopsy; D001794:Blood Pressure; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003929:Diabetic Neuropathies / Q000523:psychology*; D003927:Diet, Diabetic; D015444:Exercise; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008019:Life Style; D008297:Male; D008824:Michigan; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D011236:Prediabetic State / Q000523:psychology*; D012867:Skin / Q000294:innervation* / Q000473:pathology; D014280:Triglycerides / Q000097:blood; D014589:Utah
chemical_list: D014280:Triglycerides; D002784:Cholesterol