Exercise as Therapy for Diabetic and Prediabetic Neuropathy
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Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function.
KeywordsDiabetic neuropathy Exercise Metabolic syndrome Human trials Sedentary behavior Actigraphy
All authors of this paper have funding from NIH that is supporting this work (NIH R01 DK064814).
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Conflict of Interest
J. Robinson Singleton, A. Gordon Smith, and Robin L. Marcus declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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