Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients.
OBJECTIVE
Unmyelinated cutaneous axons are vulnerable to physical and metabolic injury, but also capable of rapid regeneration. This balance may help determine risk for peripheral neuropathy associated with diabetes or metabolic syndrome. Capsaicin application for 48 hours induces cutaneous fibers to die back into the dermis. Regrowth can be monitored by serial skin biopsies to determine intraepidermal nerve fiber density (IENFD). We used this capsaicin axotomy technique to examine the effects of exercise on cutaneous regenerative capacity in the setting of metabolic syndrome.


METHODS
Baseline ankle IENFD and 30-day cutaneous regeneration after thigh capsaicin axotomy were compared for participants with type 2 diabetes (n = 35) or metabolic syndrome (n = 32) without symptoms or examination evidence of neuropathy. Thirty-six participants (17 with metabolic syndrome) then joined twice weekly observed exercise and lifestyle counseling. Axotomy regeneration was repeated in month 4 during this intervention.


RESULTS
Baseline distal leg IENFD was significantly reduced for both metabolic syndrome and diabetic groups. With exercise, participants significantly improved exercise capacity and lower extremity power. Following exercise, 30-day reinnervation rate improved (0.051 ± 0.027 fibers/mm/day before vs 0.072 ± 0.030 after exercise, p = 0.002). Those who achieved improvement in more metabolic syndrome features experienced a greater degree of 30-day reinnervation (p < 0.012).


CONCLUSIONS
Metabolic syndrome was associated with reduced baseline IENFD and cutaneous regeneration capacity comparable to that seen in diabetes. Exercise-induced improvement in metabolic syndrome features increased cutaneous regenerative capacity. The results underscore the potential benefit to peripheral nerve function of a behavioral modification approach to metabolic improvement.
Departments of Neurology, University of Utah, Salt Lake City, UT.
J Robinson
JR
Singleton
Robin L
RL
Marcus
Margaret K
MK
Lessard
Justin E
JE
Jackson
A Gordon
AG
Smith
D000279:Administration, Cutaneous; D001706:Biopsy; D002211:Capsaicin / Q000627:therapeutic use; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000473:pathology / Q000534:rehabilitation; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000294:innervation*; D012871:Skin Diseases / Q000188:drug therapy / Q000209:etiology*; D013997:Time Factors
D002211:Capsaicin