Exercise increases cutaneous nerve density in diabetic patients without neuropathy

John R Singleton, Robin L Marcus, Justin E Jackson, Margaret K Lessard, Timothy E Graham, Albert G Smith, John R Singleton, Robin L Marcus, Justin E Jackson, Margaret K Lessard, Timothy E Graham, Albert G Smith

Abstract

Early diabetic neuropathy is characterized by loss of unmyelinated axons, resulting in pain, numbness, and progressive decline in intraepidermal nerve fiber density. Patients with type 2 diabetes, without neuropathy, were assigned to quarterly lifestyle counseling (N = 40) or structured, supervised weekly exercise (N = 60) for 1 year. Distal leg IENFD significantly increased in the exercise cohort and remained unchanged in the counseling cohort (1.5 ± 3.6 vs. -0.1 ± 3.2 fibers/mm, P = 0.03). These results suggest preclinical injury to unmyelinated axons is potentially reversible, and that IENFD may be a responsive biomarker useful in future neuropathy prevention clinical trials.

Figures

Figure 1
Figure 1
Study progress, with numbers of participants screened, evaluated at baseline, assigned to study groups, and completing 12 month assessment.
Figure 2
Figure 2
Supervised exercise over 12 months improves intraepidermal nerve fiber density (IENFD) in non-neuropathic patients with diabetes. Bars represent change in IENFD 0–12 months ± SEM at ankle or proximal thigh for participants assigned to supervised exercise (solid), or counseling (unfilled) groups. Participants receiving standard-of-care counseling showed stasis or slow decline in fiber density.

References

    1. Smith AG, Howard JR, Kroll R, et al. The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci. 2005;228:65–69.
    1. Lauria G, Bakkers M, Schmitz C, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15:202–207.
    1. Callaghan B, Feldman E. The metabolic syndrome and neuropathy: therapeutic challenges and opportunities. Ann Neurol. 2013;74:397–403.
    1. Smith AG, Singleton JR. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. J Diabetes Complications. 2013;27:436–442.
    1. Guilford BL, Ryals JM, Wright DE. Phenotypic changes in diabetic neuropathy induced by a high-fat diet in diabetic C57BL/6 mice. Exp Diabetes Res. 2011;2011:848307.
    1. Stenkamp-Strahm CM, Kappmeyer AJ, Schmalz JT, et al. High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes. Cell Tissue Res. 2013;354:381–394.
    1. Lupachyk S, Watcho P, Hasanova N, et al. Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative-nitrosative stress. Free Radic Biol Med. 2012;52:1255–1263.
    1. Vincent AM, Hayes JM, McLean LL, et al. Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes. 2009;58:2376–2385.
    1. Kluding PM, Pasnoor M, Singh R, et al. The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy. J Diabetes Complications. 2012;26:424–429.
    1. Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006;29:1294–1299.
    1. Feldman EL, Stevens MJ, Thomas PK, et al. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994;17:1281–1289.
    1. Singleton JR, Bixby B, Russell JW, et al. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008;13:218–227.
    1. American College of Sports Medicine. Guidelines for exercise testing and prescription. Philadelphia: Lea and Febiger; 1991.
    1. Beriault K, Carpentier AC, Gagnon C, et al. Reproducibility of the 6-minute walk test in obese adults. Int J Sports Med. 2009;30:725–727.
    1. Bassey EJ, Short AH. A new method for measuring power output in a single leg extension: feasibility, reliability and validity. Eur J Appl Physiol Occup Physiol. 1990;60:385–390.
    1. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343–1350.
    1. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377–381.
    1. Dyck PJ, Norell JE, Tritschler H, et al. Challenges in design of multicenter trials: end points assessed longitudinally for change and monotonicity. Diabetes Care. 2007;30:2619–2625.
    1. Boyd AL, Barlow PM, Pittenger GL, et al. Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2010;3:431–437.
    1. Arimura A, Deguchi T, Sugimoto K, et al. Intraepidermal nerve fiber density and nerve conduction study parameters correlate with clinical staging of diabetic polyneuropathy. Diabetes Res Clin Pract. 2013;99:24–29.

Source: PubMed

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