Physical activity and dietary interventions in diabetic neuropathy: a systematic review
Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes.
The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome.
Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures.
Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.
KeywordsDiabetic neuropathy Exercise Diet Dysautonomia Sirtuins
Supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1R01DK107007-01A1, the Office of Research Development, Department of Veterans Affairs (Biomedical and Laboratory Research Service and Rehabilitation Research and Development, 101RX001030), the Diabetes Action Research and Education Foundation, and the Baltimore GRECC (JWR), 1K2RX001651 (LAZ).
- 1.Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281Google Scholar
- 2.Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’Brien PC, Melton LJ III, Service FJ (1993) The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43:817–824CrossRefGoogle Scholar
- 3.Dyck PJB, Dyck PJ (1999) Diabetic polyneuropathy. In: Dyck PJ, Thomas PK (eds) Diabetic neuropathy. W.B. Saunders Company, Philadelphia, pp 255–278Google Scholar
- 4.Albers JW, Herman WH, Pop-Busui R, Martin CL, Cleary P, Waberski B (2007) Subclinical neuropathy among Diabetes Control and Complications Trial participants without diagnosable neuropathy at trial completion: possible predictors of incident neuropathy? Diabetes Care 30:2613–2618CrossRefGoogle Scholar
- 15.Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J, European Federation of Neurological Societies, Peripheral Nerve Society (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 17:903–912 (e944–909) Google Scholar
- 17.Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O’Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D (2003) The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care 26:770–776Google Scholar
- 20.Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ (2011) Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 34:2054–2060CrossRefGoogle Scholar
- 21.Chandrasekaran KCC, Sagi AR, Russell JW (2016) A nicotinamide adenine nucleotide (NAD+) precursor is a potential therapy for diabetic neuropathy (abstract). In: ICNMD 2016: abstract book for the 14th International Congress on Neuromuscular Diseases, July 5–9, 2016 Toronto, Canada. J Neuromuscul Dis 3:S86Google Scholar
- 23.Liu D, Gharavi R, Pitta M, Gleichmann M, Mattson MP (2009) Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons. Neuromolecular Med 11:28–42Google Scholar
- 24.Min SW, Sohn PD, Cho SH, Swanson RA, Gan L (2013) Sirtuins in neurodegenerative diseases: an update on potential mechanisms. Front Aging Neurosci 5:53Google Scholar
- 26.Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J (2012) The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab 15:838–847CrossRefGoogle Scholar
- 27.Avinash Rao S, Priyanka S, Chen C, Chandrasekaran K, Russell JW (2015) Administration of either nicotinamide mononucleotide (NMN) or over expression of SIRT1 prevents and treats peripheral neuropathy in type 1 and type 2 diabetic mouse models (abstract). In: 3rd International Conference and Exhibition on Neurology and Therapeutics. J Neurol Neurophysiol 6:3Google Scholar
- 29.Russell JW, Chandrasekaran K, Choi J, Chen H (2013) Nicotinamide adenine nucleotide (NAD+) regulation of sirtuin 1 (SIRT1) in the treatment of diabetic neuropathy (abstract). Ann Neurol p S95Google Scholar
- 37.Pritchard N, Edwards K, Russell AW, Perkins BA, Malik RA, Efron N (2015) Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care 38:671–675Google Scholar
- 47.Müller-Stich BP, Fischer L, Kenngott HG, Gondan M, Senft J, Clemens G, Nickel F, Fleming T, Nawroth PP, Büchler MW (2013) Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization—results of a prospective cohort study (DiaSurg 1 study). Ann Surg 258:760–765 (discussion 765–766) CrossRefGoogle Scholar
- 55.Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P (2011) Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 27:639–653Google Scholar
- 56.Grisé KN, Olver TD, McDonald MW, Dey A, Jiang M, Lacefield JC, Shoemaker JK, Noble EG, Melling CW (2016) High intensity aerobic exercise training improves deficits of cardiovascular autonomic function in a rat model of type 1 diabetes mellitus with moderate hyperglycemia. J Diabetes Res 2016:8164518CrossRefGoogle Scholar
- 61.The Diabetes Control and Complications Trial Research Group (1998) The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia 41:416–423Google Scholar
- 62.Pop-Busui R, Low PA, Waberski BH, Martin CL, Albers JW, Feldman EL, Sommer C, Cleary PA, Lachin JM, Herman WH (2009) Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation 119:2886–2893Google Scholar
- 67.Bhagyalakshmi S, Nagaraja H, Anupama B, Ramesh B, Prabha A, Niranjan M, Shreedhara A (2007) Effect of supervised integrated exercise on heart rate variability in type 2 diabetes mellitus. Kardiol Pol 65:363–368 (discussion 369) Google Scholar
- 71.American Diabetes Association (2018) 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018. Diabetes Care 41:S13–S27Google Scholar
- 75.Burr JF, Shephard RJ, Riddell MC (2012) Physical activity in type 1 diabetes mellitus: assessing risks for physical activity clearance and prescription. Can Fam Physician 58:533–535Google Scholar
- 78.Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B, American College of Sports Medicine, American Diabetes Association (2010) Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement executive summary. Diabetes Care 33:2692–2696Google Scholar