Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients

Abstract

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).

Interpretation: 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.

Conflict of interest statement

None of the authors reports a potential conflict of interest for the study or its submission.

© 2014 American Neurological Association.

Figures

Figure 1

Supervised exercise and dietary counseling significantly improved cutaneous reinnervation. (A) Distal thigh (DT) intraepidermal nerve fiber density (IENFD), before capsaicin treatment, was similar at baseline (BL) and following 3 months of exercise (postExerc). 48 hours of capsaicin patch reduced IENFD (B). Following exercise, there was significant improvement in cutaneous reinnervation expressed as a percentage of pre-capsaicin IENFD (B) and reinnervation rate (fibers/mm/day) (C) measured 30 days after completion of capsaicin axotomy. For each figure open markers represent baseline and filled markers represent post-exercise values. Values shown are expressed as mean +/− 1SD, and p values represent t-test for pair wise comparison. N=32.

Figure 2

Thirty-day reinnervation rate (fibers/mm/day) was greater for participants who improved measures of Metabolic Syndrome compared to those who did not. Participants were dichotomized into those who achieved improvement (unfilled bars), versus stability or worsening (filled bars) of each metabolic measure. Reinnervation rate differences associated with improvement in fasting glucose and HgbA1c were statistical significant by between group t-test comparison. N=32. Values are expressed as mean +/− 1SD. Gluc- fasting glucose, HgbA1c- hemoglobin A1c, BMI- body mass index, TGs- triglycerides.