Title:Exercise as Treatment for Neuropathy in the Setting of Diabetes and Prediabetic
Metabolic Syndrome: A Review of Animal Models and Human Trials
Volume: 18
Issue: 5
Author(s): J. Robinson Singleton*, Stormy Foster-Palmer and Robin L. Marcus
Affiliation:
- Department of Neurology, University of Utah, UT, United States
Abstract:
Background: Peripheral neuropathy is among the most common complications of diabetes,
but a phenotypically identical distal sensory predominant, painful axonopathy afflicts patients
with prediabetic metabolic syndrome, exemplifying a spectrum of risk and continuity of
pathogenesis. No pharmacological treatment convincingly improves neuropathy in the setting of
metabolic syndrome, but evolving data suggest that exercise may be a promising alternative.
Objective: The aim of the study was to review in depth the current literature regarding exercise
treatment of metabolic syndrome neuropathy in humans and animal models, highlight the diverse
mechanisms by which exercise exerts beneficial effects, and examine adherence limitations, safety
aspects, modes and dose of exercise.
Results: Rodent models that recapitulate the organismal milieu of prediabetic metabolic syndrome
and the phenotype of its neuropathy provide a strong platform to dissect exercise effects on neuropathy
pathogenesis. In these models, exercise reverses hyperglycemia and consequent oxidative
and nitrosative stress, improves microvascular vasoreactivity, enhances axonal transport, ameliorates
the lipotoxicity and inflammatory effects of hyperlipidemia and obesity, supports neuronal
survival and regeneration following injury, and enhances mitochondrial bioenergetics at the distal
axon. Prospective human studies are limited in scale but suggest exercise to improve cutaneous
nerve regenerative capacity, neuropathic pain, and task-specific functional performance measures
of gait and balance. Like other heath behavioral interventions, the benefits of exercise are limited
by patient adherence.
Conclusion: Exercise is an integrative therapy that potently reduces cellular inflammatory state
and improves distal axonal oxidative metabolism to ameliorate features of neuropathy in metabolic
syndrome. The intensity of exercise need not improve cardinal features of metabolic syndrome, including
weight, glucose control, to exert beneficial effects.
