Lifestyle intervention for pre-diabetic neuropathy.
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.
Smith
A Gordon
AG
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
Russell
James
J
Feldman
Eva L
EL
Goldstein
Jonathan
J
Peltier
Amanda
A
Smith
Sheldon
S
Hamwi
Jouhaina
J
Pollari
Donald
D
Bixby
Billie
B
Howard
James
J
Singleton
J Robinson
JR
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
D014280:Triglycerides; D002784:Cholesterol