Exercise as Treatment for Neuropathy in the Setting of Diabetes and Prediabetic
Metabolic Syndrome: A Review of Animal Models and Human Trials

J.    Robinson    Singleton; Stormy       Foster-Palmer; Robin    L.    Marcus
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.
[1] 
Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol  2015; 3(11): 866-75.
[http://dx.doi.org/10.1016/S2213-8587(15)00291-0] [PMID: 26377054] 
[2] 
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med  2002; 346(6): 393-403.
[http://dx.doi.org/10.1056/NEJMoa012512] [PMID: 11832527] 
[3] 
Nathan DM, Genuth S, Lachin J, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med  1993; 329(14): 977-86.
[http://dx.doi.org/10.1056/NEJM199309303291401] [PMID: 8366922] 
[4] 
Callaghan BC, Little A, Feldman E, Hughes R. Enhanced glycemic control for preventing and treating diabetic neuropathy.  Cochrane Database Syst Rev 2012; 6(6): CD007543.
[http://dx.doi.org/10.1002/14651858.CD007543.pub2] [PMID: 22696371] 
[5] 
Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial. Lancet  2010; 376(9739): 419-30.
[http://dx.doi.org/10.1016/S0140-6736(10)60576-4] [PMID: 20594588] 
[6] 
Navarro X, Sutherland DE, Kennedy WR. Long-term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol  1997; 42(5): 727-36.
[http://dx.doi.org/10.1002/ana.410420509] [PMID: 9392572] 
[7] 
Mehra S, Tavakoli M, Kallinikos PA, et al. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care  2007; 30(10): 2608-12.
[http://dx.doi.org/10.2337/dc07-0870] [PMID: 17623821] 
[8] 
Tavakoli M, Mitu-Pretorian M, Petropoulos IN, et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes  2013; 62(1): 254-60.
[http://dx.doi.org/10.2337/db12-0574] [PMID: 23002037] 
[9] 
Yagihashi S, Yamagishi SI, Wada Ri R, et al. Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor. Brain  2001; 124(Pt 12): 2448-58.
[http://dx.doi.org/10.1093/brain/124.12.2448] [PMID: 11701599] 
[10] 
Krentz AJ, Honigsberger L, Ellis SH, Hardman M, Nattrass M. A 12-month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy. Diabet Med  1992; 9(5): 463-8.
[http://dx.doi.org/10.1111/j.1464-5491.1992.tb01818.x] [PMID: 1611835] 
[11] 
Coppey LJ, Davidson EP, Rinehart TW, et al. ACE inhibitor or angiotensin II receptor antagonist attenuates diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetes  2006; 55(2): 341-8.
[http://dx.doi.org/10.2337/diabetes.55.02.06.db05-0885] [PMID: 16443766] 
[12] 
Malik R, Williamson S, Abbott C. Effect of the angiotensin converting enzyme inhibitor trandalopril on human diabetic neuropathy: A randomised controlled trial. Lancet  1998; 352: 1978-81.
[http://dx.doi.org/10.1016/S0140-6736(98)02478-7] [PMID: 9872248] 
[13] 
Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes  1997; 46(Suppl. 2): S62-6.
[http://dx.doi.org/10.2337/diab.46.2.S62] [PMID: 9285502] 
[14] 
Ziegler D, Sohr CG, Nourooz-Zadeh J. Oxidative stress and antioxidant defense in relation to the severity of diabetic polyneuropathy and cardiovascular autonomic neuropathy. Diabetes Care  2004; 27(9): 2178-83.
[http://dx.doi.org/10.2337/diacare.27.9.2178] [PMID: 15333481] 
[15] 
Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia  2001; 44(11): 1973-88.
[http://dx.doi.org/10.1007/s001250100001] [PMID: 11719828] 
[16] 
Greene DA, Arezzo JC, Brown MB. Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Neurology  1999; 53(3): 580-91.
[http://dx.doi.org/10.1212/WNL.53.3.580] [PMID: 10449124] 
[17] 
Kihara M, Mitsui Y, Shioyama M, et al. Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in experimental diabetic neuropathy of rat. Neurosci Lett  2001; 310(2-3): 81-4.
[http://dx.doi.org/10.1016/S0304-3940(01)02052-3] [PMID: 11585572] 
[18] 
Pfeifer MA, Schumer MP. Clinical trials of diabetic neuropathy: past, present, and future. Diabetes  1995; 44(12): 1355-61.
[http://dx.doi.org/10.2337/diab.44.12.1355] [PMID: 7589838] 
[19] 
Dyck PJ, Overland CJ, Low PA, et al. Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve  2010; 42(2): 157-64.
[http://dx.doi.org/10.1002/mus.21661] [PMID: 20658599] 
[20] 
Mojaddidi M, Quattrini C, Tavakoli M, Malik RA. Recent developments in the assessment of efficacy in clinical trials of diabetic neuropathy. Curr Diab Rep  2005; 5(6): 417-22.
[http://dx.doi.org/10.1007/s11892-005-0048-6] [PMID: 16316591] 
[21] 
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(1): 65-9.
[http://dx.doi.org/10.1016/j.jns.2004.09.032] [PMID: 15607212] 
[22] 
Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes  2003; 52(12): 2867-73.
[http://dx.doi.org/10.2337/diabetes.52.12.2867] [PMID: 14633845] 
[23] 
Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig  2017; 8(5): 646-55.
[http://dx.doi.org/10.1111/jdi.12650] [PMID: 28267267] 
[24] 
Ruegsegger GN, Booth FW. Health Benefits of Exercise. Cold Spring Harb Perspect Med  2018; 8(7): a029694.
[http://dx.doi.org/10.1101/cshperspect.a029694] [PMID: 28507196] 
[25] 
Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med  2002; 346(11): 793-801.
[http://dx.doi.org/10.1056/NEJMoa011858] [PMID: 11893790] 
[26] 
Kokkinos P, Myers J, Faselis C, et al. Exercise capacity and mortality in older men: A 20-year follow-up study. Circulation  2010; 122(8): 790-7.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.938852] [PMID: 20697029] 
[27] 
Greene DA, Lattimer SA, Sima AAF. Pathogenesis and prevention of diabetic neuropathy. Diabetes Metab Rev  1988; 4(3): 201-21.
[http://dx.doi.org/10.1002/dmr.5610040303] [PMID: 3293948] 
[28] 
Greene DA, Sima AA, Stevens MJ, Feldman EL, Lattimer SA. Complications: neuropathy, pathogenetic considerations. Diabetes Care  1992; 15(12): 1902-25.
[http://dx.doi.org/10.2337/diacare.15.12.1902] [PMID: 1464245] 
[29] 
Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics  2009; 6(4): 638-47.
[http://dx.doi.org/10.1016/j.nurt.2009.07.004] [PMID: 19789069] 
[30] 
Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology  2009; 57(4): 456-62.
[http://dx.doi.org/10.1016/j.neuropharm.2009.06.013] [PMID: 19555701] 
[31] 
Britland ST, Young RJ, Sharma AK, Clarke BF. Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy. Diabetes  1990; 39(8): 909-13.
[http://dx.doi.org/10.2337/diab.39.8.909] [PMID: 2373263] 
[32] 
Dyck PJ, Hansen S, Karnes J, et al. Capillary number and percentage closed in human diabetic sural nerve. Proc Natl Acad Sci USA  1985; 82(8): 2513-7.
[http://dx.doi.org/10.1073/pnas.82.8.2513] [PMID: 3857597] 
[33] 
Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes  1997; 46(Suppl. 2): S31-7.
[http://dx.doi.org/10.2337/diab.46.2.S31] [PMID: 9285496] 
[34] 
King RHM. The role of glycation in the pathogenesis of diabetic polyneuropathy. Mol Pathol  2001; 54(6): 400-8.
[PMID: 11724915] 
[35] 
Juranek JK, Geddis MS, Rosario R, Schmidt AM. Impaired slow axonal transport in diabetic peripheral nerve is independent of RAGE. Eur J Neurosci  2013; 38(8): 3159-68.
[http://dx.doi.org/10.1111/ejn.12333] [PMID: 23941591] 
[36] 
Vincent AM, Hayes JM, McLean LL, Vivekanandan-Giri A, Pennathur S, Feldman EL. Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes  2009; 58(10): 2376-85.
[http://dx.doi.org/10.2337/db09-0047] [PMID: 19592619] 
[37] 
Vincent AM, Hinder LM, Pop-Busui R, Feldman EL. Hyperlipidemia: A new therapeutic target for diabetic neuropathy. J Peripher Nerv Syst  2009; 14(4): 257-67.
[http://dx.doi.org/10.1111/j.1529-8027.2009.00237.x] [PMID: 20021567] 
[38] 
Choe EY, Wang HJ, Kwon O, et al. Variants of the adiponectin gene and diabetic microvascular complications in patients with type 2 diabetes. Metabolism  2013; 62(5): 677-85.
[http://dx.doi.org/10.1016/j.metabol.2012.11.005] [PMID: 23260797] 
[39] 
Leinninger GM, Vincent AM, Feldman EL. The role of growth factors in diabetic peripheral neuropathy. J Peripher Nerv Syst  2004; 9(1): 26-53.
[http://dx.doi.org/10.1111/j.1085-9489.2004.09105.x] [PMID: 14871451] 
[40] 
Pierson CR, Zhang W, Murakawa Y, Sima AA. Early gene responses of trophic factors in nerve regeneration differ in experimental type 1 and type 2 diabetic polyneuropathies. J Neuropathol Exp Neurol  2002; 61(10): 857-71.
[http://dx.doi.org/10.1093/jnen/61.10.857] [PMID: 12387452] 
[41] 
Christianson JA, Riekhof JT, Wright DE. Restorative effects of neurotrophin treatment on diabetes-induced cutaneous axon loss in mice. Exp Neurol  2003; 179(2): 188-99.
[http://dx.doi.org/10.1016/S0014-4886(02)00017-1] [PMID: 12618126] 
[42] 
Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. J Diabetes Investig  2018; 9(6): 1239-54.
[http://dx.doi.org/10.1111/jdi.12833] [PMID: 29533535] 
[43] 
Edwards JL, Quattrini A, Lentz SI, et al. Diabetes regulates mitochondrial biogenesis and fission in mouse neurons. Diabetologia  2010; 53(1): 160-9.
[http://dx.doi.org/10.1007/s00125-009-1553-y] [PMID: 19847394] 
[44] 
Chandrasekaran K, Anjaneyulu M, Choi J, et al. Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD+-dependent SIRT1-PGC-1α-TFAM pathway. Int Rev Neurobiol  2019; 145: 177-209.
[http://dx.doi.org/10.1016/bs.irn.2019.04.002] [PMID: 31208524] 
[45] 
Biessels GJ, Bril V, Calcutt NA, et al. Phenotyping animal models of diabetic neuropathy: A consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab). J Peripher Nerv Syst  2014; 19(2): 77-87.
[http://dx.doi.org/10.1111/jns5.12072] [PMID: 24934510] 
[46] 
Nakos I, Kadoglou NPE, Gkeka P, et al. Exercise training attenuates the development of cardiac autonomic dysfunction in diabetic rats. In Vivo  2018; 32(6): 1433-41.
[http://dx.doi.org/10.21873/invivo.11396] [PMID: 30348698] 
[47] 
Davidson EP, Coppey LJ, Holmes A, et al. Characterization of diabetic neuropathy in the zucker diabetic sprague-dawley rat: a new animal model for type 2 diabetes. J Diabetes Res  2014; 2014: 714273.
[http://dx.doi.org/10.1155/2014/714273] [PMID: 25371906] 
[48] 
Davidson EP, Coppey LJ, Calcutt NA, Oltman CL, Yorek MA. Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction. Diabetes Metab Res Rev  2010; 26(4): 306-18.
[http://dx.doi.org/10.1002/dmrr.1088] [PMID: 20503263] 
[49] 
Drel VR, Mashtalir N, Ilnytska O, et al. The leptin-deficient (ob/ob) mouse: A new animal model of peripheral neuropathy of type 2 diabetes and obesity. Diabetes  2006; 55(12): 3335-43.
[http://dx.doi.org/10.2337/db06-0885] [PMID: 17130477] 
[50] 
Holmes A, Coppey LJ, Davidson EP, Yorek MA. Rat models of diet-induced obesity and high fat/low dose streptozotocin type 2 diabetes: effect of reversal of high fat diet compared to treatment with enalapril or menhaden oil on glucose utilization and neuropathic endpoints. J Diabetes Res  2015; 2015: 307285.
[http://dx.doi.org/10.1155/2015/307285] [PMID: 26229968] 
[51] 
A. The role of ceramide in insulin resistance. Front Endocrinol  2019; 10: 577.
[http://dx.doi.org/10.3389/fendo.2019.00577] 
[52] 
Lila M. Oyama, Eliane B. Ribeiro, Ana R. Dâmaso, Aline de Piano. Lipotoxicity: Effects of dietary saturated and transfatty acids. Mediators Inflamm  2013; 2013: 13.
[53] 
Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr  2009; 139(1): 1-4.
[http://dx.doi.org/10.3945/jn.108.098269] [PMID: 19056664] 
[54] 
Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res  2006; 45(1): 42-72.
[http://dx.doi.org/10.1016/j.plipres.2005.11.002] [PMID: 16445986] 
[55] 
Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord  2008; 9(4): 301-14.
[http://dx.doi.org/10.1007/s11154-008-9104-2] [PMID: 18709457] 
[56] 
Vincent AM, Olzmann JA, Brownlee M, Sivitz WI, Russell JW. Uncoupling proteins prevent glucose-induced neuronal oxidative stress and programmed cell death. Diabetes  2004; 53(3): 726-34.
[http://dx.doi.org/10.2337/diabetes.53.3.726] [PMID: 14988258] 
[57] 
Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxid Med Cell Longev  2013; 2013: 168039.
[http://dx.doi.org/10.1155/2013/168039] [PMID: 23738033] 
[58] 
Román-Pintos LMV-RG, Rodríguez-Carrizalez AD, Miranda-Díaz AG. CardonaMuñoz EG. Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function.  J Diabetes Res 2016; 2016: 3425617.
[http://dx.doi.org/10.1155/2016/3425617] [PMID: 28058263] 
[59] 
Albers J, Pop-Busui R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. Curr Neol Neurosci Rep  2014; 14(8)
[http://dx.doi.org/10.1007/s11910-014-0473-5] 
[60] 
Myslicki J, Shearer J, Hittel DS, Hughey CC, Belke DD. Diabetol Metab Syndr. 2014;6(1):96. Published 2014 Sep 9. O-GlcNAc modification is associated with insulin sensitivity in the whole blood of healthy young adult males. Diabetol Metab Syndr  2014; 6(1): 96.
[http://dx.doi.org/10.1186/1758-5996-6-96] [PMID: 25228926] 
[61] 
Kwak HB. Exercise and obesity-induced insulin resistance in skeletal muscle. Integr Med Res  2013; 2(4): 131-8.
[http://dx.doi.org/10.1016/j.imr.2013.09.004] [PMID: 28664064] 
[62] 
Loganathan R, Novikova L, Boulatnikov IG, Smirnova IV. Exercise-induced cardiac performance in autoimmune (type 1) diabetes is associated with a decrease in myocardial diacylglycerol. J Appl Physiol  2012; 113(5): 817-26.
[63] 
Tzeng HT, Chyuan IT, Chen WY. Shaping of innate immune response by fatty acid metabolite palmitate. Cells  2019; 8(12): 1633.
[http://dx.doi.org/10.3390/cells8121633] [PMID: 31847240] 
[64] 
Chavez JA, Knotts TA, Wang L-P, et al. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem  2003; 278(12): 10297-303.
[http://dx.doi.org/10.1074/jbc.M212307200] [PMID: 12525490] 
[65] 
Tzeng HT, Chyuan IT, Chen WY. Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate. Cells  2019; 8(12): E1633.
[http://dx.doi.org/10.3390/cells8121633] [PMID: 31847240] 
[66] 
Rumora AELG, LoGrasso G, Hayes JM, et al. The divergent roles of dietary saturated and monounsaturated fatty acids on nerve function in murine models of obesity. J Neurosci  2019; 39(19): 3770-81.
[http://dx.doi.org/10.1523/JNEUROSCI.3173-18.2019] [PMID: 30886017] 
[67] 
Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. Eur J Clin Invest  2017; 47(8): 600-11.
[http://dx.doi.org/10.1111/eci.12781] [PMID: 28722106] 
[68] 
Haley MJ, Mullard G, Hollywood K A, Cooper G J, Dunn W B, Lawrence C B. Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice. Dis Model Mech  2017; 10(10): 1229-43.
[http://dx.doi.org/10.1242/dmm.030411] 
[69] 
Schilling JD, Machkovech HM, He L, et al. Palmitate and lipopolysaccharide trigger synergistic ceramide production in primary macrophages. J Biol Chem  2013; 288(5): 2923-32.
[http://dx.doi.org/10.1074/jbc.M112.419978] [PMID: 23250746] 
[70] 
Holland WL, Brozinick JT, Wang L-P, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab  2007; 5(3): 167-79.
[http://dx.doi.org/10.1016/j.cmet.2007.01.002] [PMID: 17339025] 
[71] 
Bradley RL. Jeon, Justin Y., Liu, Fen-Fen, and Maratos-Flier, Eleftheria. Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in dietinduced obese mice. Am J Phys  2008; 295(3): E586-94.
[PMID: 18577694] 
[72] 
Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget  2017; 9(6): 7204-18.
[http://dx.doi.org/10.18632/oncotarget.23208] [PMID: 29467962] 
[73] 
Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis  2019; 10(2): 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589] 
[74] 
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci  2019; 20(13): 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572] 
[75] 
Chiu IM, von Hehn CA, Woolf CJ. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci  2012; 15(8): 1063-7.
[http://dx.doi.org/10.1038/nn.3144] [PMID: 22837035] 
[76] 
Di Cara F, Andreoletti P, Trompier D, et al. Peroxisomes in immune response and inflammation. Int J Mol Sci  2019; 20(16): 3877.
[http://dx.doi.org/10.3390/ijms20163877] [PMID: 31398943] 
[77] 
Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis  2015; 14(121): 121.
[http://dx.doi.org/10.1186/s12944-015-0123-1] [PMID: 26415887] 
[78] 
Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation.  Sig Transduct Target Ther 2017; p. 2.
[79] 
Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol  2009; 1(6): a001651.
[http://dx.doi.org/10.1101/cshperspect.a001651] [PMID: 20457564] 
[80] 
Wullaert A, Bonnet MC, Pasparakis M. NF-κB in the regulation of epithelial homeostasis and inflammation. Cell Res  2011; 21(1): 146-58.
[http://dx.doi.org/10.1038/cr.2010.175] [PMID: 21151201] 
[81] 
Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta  2010; 411(11-12): 785-93.
[http://dx.doi.org/10.1016/j.cca.2010.02.069] [PMID: 20188719] 
[82] 
You T, Arsenis NC, Disanzo BL, Lamonte MJ. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms. Sports Med  2013; 43(4): 243-56.
[http://dx.doi.org/10.1007/s40279-013-0023-3] [PMID: 23494259] 
[83] 
Suzuki K. Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules  2019; 9(6): 223.
[http://dx.doi.org/10.3390/biom9060223] [PMID: 31181700] 
[84] 
Zheng Guohua QP, Rui Xia, Lin Huiying, Ye Bingzhao, Jing Tao, Chen Lidian. Effect of aerobic exercise on inflammatory markers in healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials Frontiers in Aging Neuroscience  2019; 11: 98.
[http://dx.doi.org/10.3389/fnagi.2019.00098] 
[85] 
Schwartz EA, Zhang WY, Karnik SK, et al. Nutrient modification of the innate immune response: A novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler Thromb Vasc Biol  2010; 30(4): 802-8.
[http://dx.doi.org/10.1161/ATVBAHA.109.201681] [PMID: 20110572] 
[86] 
Dasu MRJI. Free fatty acids in the presence of high glucose amplify monocyte inflammationviaToll-like receptors. Am J Physiol Endocrinol Metab  2011; 300: E145E54.
[http://dx.doi.org/10.1152/ajpendo.00490.2010] 
[87] 
Chenxu G, Minxuan X, Yuting Q, et al. Loss of RIP3 initiates annihilation of high-fat diet initialized nonalcoholic hepatosteatosis: A mechanism involving Toll-like receptor 4 and oxidative stress. Free Radic Biol Med  2019; 134: 23-41.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.12.034] [PMID: 30599260] 
[88] 
Bernardi S, Marcuzzi A, Piscianz E, Tommasini A, Fabris B. The complex interplay between lipids, immune system and interleukins in cardio-metabolic diseases. Int J Mol Sci  2018; 19(12): 4058.
[http://dx.doi.org/10.3390/ijms19124058] [PMID: 30558209] 
[89] 
Zhang J-M, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin  2007; 45(2): 27-37.
[http://dx.doi.org/10.1097/AIA.0b013e318034194e] [PMID: 17426506] 
[90] 
Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev  2011; 22(4): 189-95.
[http://dx.doi.org/10.1016/j.cytogfr.2011.10.001] [PMID: 22019906] 
[91] 
Dembic Z. The Cytokines of the Immune System : The Role of Cytokines in Disease Related to Immune Response.Elsevier Science & Technology. 2015.
[92] 
 Ren K, Torres R. Role of interleukin-1β during pain and inflammation. Brain Res Rev 2009; 60(1): 57-64.
[http://dx.doi.org/10.1016/j.brainresrev.2008.12.020] 
[93] 
Leguisamo NMLA, Lehnen AM, Machado UF, et al. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome. Cardiovasc Diabetol  2012; 11(100): 100.
[http://dx.doi.org/10.1186/1475-2840-11-100] [PMID: 22897936] 
[94] 
 Li X, Zhu J, Liu N, Liu J, Zhang Z. TNF-Alpha in peripheral neuropathy patients with impaired glucose regulation. J Diabetes Res 2017; 2017: 7024024.
[http://dx.doi.org/10.1155/2017/7024024] [PMID: 28251164 ] 
[95] 
 Mu ZP, Wang YG, Li CQ, et al. Association between tumor necrosis factor-α and diabetic peripheral neuropathy in patients with type 2 diabetes: A meta-analysis. Mol Neurobiol 2017; 54(2): 983-96.
[http://dx.doi.org/10.1007/s12035-016-9702-z] [PMID: 26797519] 
[96] 
Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neuropathy: Where are we now and where to go? J Diabetes Investig  2011; 2(1): 18-32.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00070.x] [PMID: 24843457] 
[97] 
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(5): 424-9.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.05.007] [PMID: 22717465] 
[98] 
Yamakawa I, Kojima H, Terashima T, et al. Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab  2011; 301(5): E844-52.
[http://dx.doi.org/10.1152/ajpendo.00029.2011] [PMID: 21810933] 
[99] 
Vieira  VJ, Valentine RJ, Wilund KR, Antao N, Baynard T, Woods JA. Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice. Am J Physiol Endocrinol Metab  2009; 296(5): E1164-71.
[http://dx.doi.org/10.1152/ajpendo.00054.2009] [PMID: 19276393] 
[100] 
Broderick TL, Sennott JM, Gutkowska J, Jankowski M. Anti-inflammatory and angiogenic effects of exercise training in cardiac muscle of diabetic mice. Diabetes Metab Syndr Obes  2019; 12: 565-73.
[http://dx.doi.org/10.2147/DMSO.S197127] [PMID: 31118719] 
[101] 
Liu HW, Kao HH, Wu CH. Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice. Nutr Metab (Lond)  2019; 16(22): 22.
[http://dx.doi.org/10.1186/s12986-019-0349-4] [PMID: 30988688] 
[102] 
Kawanishi N, Yano H, Mizokami T, Takahashi M, Oyanagi E, Suzuki K. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice. Brain Behav Immun  2012; 26(6): 931-41.
[http://dx.doi.org/10.1016/j.bbi.2012.04.006] [PMID: 22554494] 
[103] 
Nadine Gehrke JB, Yvonne Huber, Beate K, Straub PR, Galle PS, Jörn M. Schattenberg Voluntary exercise in mice fed an obesogenic diet alters the hepatic immune phenotype and improves metabolic parameters- an animal model of life style intervention inf NAFLD. Sci Rep  2019; 9(4007)
[104] 
Belotto MFMJ, Magdalon J, Rodrigues HG, et al. Moderate exercise improves leucocyte function and decreases inflammation in diabetes. Clin Exp Immunol  2010; 162(2): 237-43.
[http://dx.doi.org/10.1111/j.1365-2249.2010.04240.x] [PMID: 20846161] 
[105] 
Roberto Codella GL. Codella R, Lanzoni G, Zoso A, et al. Moderate intensity training impact on the inflammatory status and glycemic profiles in nod mice. J Diabetes Res  2015; 2015: 11.
[http://dx.doi.org/10.1155/2015/737586] [PMID: 26347378] 
[106] 
Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab  2009; 94(6): 2157-63.
[http://dx.doi.org/10.1210/jc.2008-2385] [PMID: 19276232] 
[107] 
Pop-Busui R, Ang L, Holmes C, Gallagher K, Feldman EL. Inflammation as a therapeutic target for diabetic neuropathies. Curr Diab Rep  2016; 16(3): 29.
[http://dx.doi.org/10.1007/s11892-016-0727-5] [PMID: 26897744] 
[108] 
Ristikj-Stomnaroska D, Risteska-Nejashmikj V, Papazova M. Role of inflammation in the pathogenesis of diabetic peripheral neuropathy. Open Access Maced J Med Sci  2019; 7(14): 2267-70.
[http://dx.doi.org/10.3889/oamjms.2019.646] [PMID: 31592273] 
[109] 
Teixeira de Lemos E, Pinto R, Oliveira J, et al. Differential effects of acute (extenuating) and chronic (training) exercise on inflammation and oxidative stress status in an animal model of type 2 diabetes mellitus. Mediators Inflamm  2011; 2011: 253061.
[http://dx.doi.org/10.1155/2011/253061] [PMID: 22174491] 
[110] 
Golbidi S, Badran M, Laher I. Antioxidant and anti-inflammatory effects of exercise in diabetic patients. Exp Diabetes Res  2012; 2012: 941868.
[http://dx.doi.org/10.1155/2012/941868] [PMID: 22007193] 
[111] 
Groover AL, Ryals JM, Guilford BL, Wilson NM, Christianson JA, Wright DE. Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice. Pain  2013; 154(12): 2658-67.
[http://dx.doi.org/10.1016/j.pain.2013.07.052] [PMID: 23932909] 
[112] 
Marc D. Cook SAM, Collette Williams, Keith Whitlock, Matthew A Wallig, Brandt D Pence, Jeffrey A Woods. Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis. Brain Behav Immun  2013; 33: 46-56.
[http://dx.doi.org/10.1016/j.bbi.2013.05.005] 
[113] 
Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest  2001; 108(9): 1341-8.
[http://dx.doi.org/10.1172/JCI11235] [PMID: 11696579] 
[114] 
Stangel M, Zettl UK, Mix E, et al. H2O2 and nitric oxide-mediated oxidative stress induce apoptosis in rat skeletal muscle myoblasts. J Neuropathol Exp Neurol  1996; 55(1): 36-43.
[http://dx.doi.org/10.1097/00005072-199601000-00004] [PMID: 8558170] 
[115] 
Ukkola O, Santaniemi M. Adiponectin: A link between excess adiposity and associated comorbidities? J Mol Med (Berl)  2002; 80(11): 696-702.
[http://dx.doi.org/10.1007/s00109-002-0378-7] [PMID: 12436346] 
[116] 
Sonobe T, Tsuchimochi H, Schwenke DO, Pearson JT, Shirai M. Treadmill running improves hindlimb arteriolar endothelial function in type 1 diabetic mice as visualized by X-ray microangiography. Cardiovasc Diabetol  2015; 14: 51.
[http://dx.doi.org/10.1186/s12933-015-0217-0] [PMID: 25964060] 
[117] 
Chakraphan D, Sridulyakul P, Thipakorn B, Bunnag S, Huxley VH, Patumraj S. Attenuation of endothelial dysfunction by exercise training in STZ-induced diabetic rats. Clin Hemorheol Microcirc  2005; 32(3): 217-26.
[PMID: 15851841] 
[118] 
Zanjani SB, Chodari L, Bavil FM, Sadeghzadeh P, Shahabi P. Effect of voluntary exercise on intracellular signalling pathways of angiogenesis in the sciatic nerve of type 1 diabetic castrated male rats. Physiol Int  2019; 106(1): 39-47.
[http://dx.doi.org/10.1556/2060.106.2019.08] [PMID: 30888220] 
[119] 
Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: A review. Diabetologia  2001; 44(2): 129-46.
[http://dx.doi.org/10.1007/s001250051591] [PMID: 11270668] 
[120] 
Duran-Jimenez B, Dobler D, Moffatt S, et al. Advanced glycation end products in extracellular matrix proteins contribute to the failure of sensory nerve regeneration in diabetes. Diabetes  2009; 58(12): 2893-903.
[http://dx.doi.org/10.2337/db09-0320] [PMID: 19720799] 
[121] 
Sugimoto K, Yasujima M, Yagihashi S. Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des  2008; 14(10): 953-61.
[http://dx.doi.org/10.2174/138161208784139774] [PMID: 18473845] 
[122] 
de la Hoz CL, Cheng C, Fernyhough P, Zochodne DW. A model of chronic diabetic polyneuropathy: benefits from intranasal insulin are modified by sex and RAGE deletion. Am J Physiol Endocrinol Metab  2017; 312(5): E407-19.
[http://dx.doi.org/10.1152/ajpendo.00444.2016] [PMID: 28223295] 
[123] 
Tomlinson DR, Mayer JH. Defects of axonal transport in diabetes mellitus-a possible contribution to the aetiology of diabetic neuropathy. J Auton Pharmacol  1984; 4(1): 59-72.
[http://dx.doi.org/10.1111/j.1474-8673.1984.tb00434.x] [PMID: 6201487] 
[124] 
Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol  2017; 81(6): 772-81.
[http://dx.doi.org/10.1002/ana.24951] [PMID: 28486769] 
[125] 
Köchli S, Endes K, Trinkler M, Mondoux M, Zahner L, Hanssen H. Association of physical fitness with skin autofluorescence-derived advanced glycation end products in children. Pediatr Res  2020; 87(6): 1106-11.
[http://dx.doi.org/10.1038/s41390-019-0694-z] [PMID: 31791044] 
[126] 
Drenth H, Zuidema SU, Krijnen WP, et al. Advanced Glycation End Products Are Associated With Physical Activity and Physical Functioning in the Older Population. J Gerontol A Biol Sci Med Sci  2018; 73(11): 1545-51.
[http://dx.doi.org/10.1093/gerona/gly108] [PMID: 29718128] 
[127] 
Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ. Contribution of receptor for advanced glycation end products to vasculature-protecting effects of exercise training in aged rats. Eur J Pharmacol  2014; 741: 186-94.
[http://dx.doi.org/10.1016/j.ejphar.2014.08.017] [PMID: 25160740] 
[128] 
Delbin MA, Davel AP, Couto GK, et al. Interaction between advanced glycation end products formation and vascular responses in femoral and coronary arteries from exercised diabetic rats. PLoS One  2012; 7(12): e53318.
[http://dx.doi.org/10.1371/journal.pone.0053318] [PMID: 23285277] 
[129] 
Jasmin BJ, Lavoie PA, Gardiner PF. Fast axonal transport of labeled proteins in motoneurons of exercise-trained rats. Am J Physiol  1988; 255(6 Pt 1): C731-6.
[http://dx.doi.org/10.1152/ajpcell.1988.255.6.C731] [PMID: 2462358] 
[130] 
Jasmin BJ, Lavoie PA, Gardiner PF. Fast axonal transport of acetylcholinesterase in rat sciatic motoneurons is enhanced following prolonged daily running, but not following swimming. Neurosci Lett  1987; 78(2): 156-60.
[http://dx.doi.org/10.1016/0304-3940(87)90625-2] [PMID: 2442673] 
[131] 
Boucher TJ, McMahon SB. Neurotrophic factors and neuropathic pain. Curr Opin Pharmacol  2001; 1(1): 66-72.
[http://dx.doi.org/10.1016/S1471-4892(01)00010-8] [PMID: 11712538] 
[132] 
Syed N, Reddy K, Yang DP, et al. Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination. J Neurosci  2010; 30(17): 6122-31.
[http://dx.doi.org/10.1523/JNEUROSCI.1681-09.2010] [PMID: 20427670] 
[133] 
Guo G, Kan M, Martinez JA, Zochodne DW. Local insulin and the rapid regrowth of diabetic epidermal axons. Neurobiol Dis  2011; 43(2): 414-21.
[http://dx.doi.org/10.1016/j.nbd.2011.04.012] [PMID: 21530660] 
[134] 
Eslami R, Gharakhanlou R, Kazemi A, Dakhili AB, Sorkhkamanzadeh G, Sheikhy A. Does Endurance Training Compensate for Neurotrophin Deficiency Following Diabetic Neuropathy? Iran Red Crescent Med J  2016; 18(10): e37757.
[http://dx.doi.org/10.5812/ircmj.37757] [PMID: 28184326] 
[135] 
Chen YW, Chiu CC, Hsieh PL, Hung CH, Wang JJ. Treadmill training combined with insulin suppresses diabetic nerve pain and cytokines in rat sciatic nerve. Anesth Analg  2015; 121(1): 239-46.
[http://dx.doi.org/10.1213/ANE.0000000000000799] [PMID: 25993391] 
[136] 
Jin HY, Lee KA, Park TS. The effect of exercise on the peripheral nerve in streptozotocin (STZ)-induced diabetic rats. Endocrine  2015; 48(3): 826-33.
[http://dx.doi.org/10.1007/s12020-014-0422-8] [PMID: 25253638] 
[137] 
Selagzi H, Buyukakilli B, Cimen B, Yilmaz N, Erdogan S. Protective and therapeutic effects of swimming exercise training on diabetic peripheral neuropathy of streptozotocin-induced diabetic rats. J Endocrinol Invest  2008; 31(11): 971-8.
[http://dx.doi.org/10.1007/BF03345634] [PMID: 19169052] 
[138] 
Singleton JR, Marcus RL, Lessard MK, Jackson JE, Smith AG. Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients. Ann Neurol  2015; 77(1): 146-53.
[http://dx.doi.org/10.1002/ana.24310] [PMID: 25388934] 
[139] 
Malysz T, Ilha J, Severo do Nascimento P, et al. Exercise training improves the soleus muscle morphology in experimental diabetic nerve regeneration. Muscle Nerve  2011; 44(4): 571-82.
[http://dx.doi.org/10.1002/mus.22133] [PMID: 21922469] 
[140] 
Molteni R, Zheng JQ, Ying Z, Gómez-Pinilla F, Twiss JL. Voluntary exercise increases axonal regeneration from sensory neurons. Proc Natl Acad Sci USA  2004; 101(22): 8473-8.
[http://dx.doi.org/10.1073/pnas.0401443101] [PMID: 15159540] 
[141] 
Li H, Shen Z, Lu Y, Lin F, Wu Y, Jiang Z. Muscle NT-3 levels increased by exercise training contribute to the improvement in caudal nerve conduction velocity in diabetic rats. Mol Med Rep  2012; 6(1): 69-74.
[PMID: 22552353] 
[142] 
Mackay CP, Kuys SS, Brauer SG. The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis. Neural Plast  2017; 2017: 4716197.
[http://dx.doi.org/10.1155/2017/4716197] [PMID: 29057125] 
[143] 
Yajima Y, Narita M, Usui A, et al. Direct evidence for the involvement of brain-derived neurotrophic factor in the development of a neuropathic pain-like state in mice. J Neurochem  2005; 93(3): 584-94.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03045.x] [PMID: 15836617] 
[144] 
Singh B, Singh V, Krishnan A, et al. Regeneration of diabetic axons is enhanced by selective knockdown of the PTEN gene. Brain  2014; 137(Pt 4): 1051-67.
[http://dx.doi.org/10.1093/brain/awu031] [PMID: 24578546] 
[145] 
Yaghoob Nezhad F, Verbrugge SAJ, Schönfelder M, Becker L, Hrabě de Angelis M, Wackerhage H. Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review. Front Physiol  2019; 10: 262.
[http://dx.doi.org/10.3389/fphys.2019.00262] [PMID: 30967789] 
[146] 
Liu G, Detloff MR, Miller KN, Santi L, Houlé JD. Exercise modulates microRNAs that affect the PTEN/mTOR pathway in rats after spinal cord injury. Exp Neurol  2012; 233(1): 447-56.
[http://dx.doi.org/10.1016/j.expneurol.2011.11.018] [PMID: 22123082] 
[147] 
Valenti MT, Deiana M, Cheri S, et al. Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis. Cells  2019; 8(7): E742.
[http://dx.doi.org/10.3390/cells8070742] [PMID: 31330975] 
[148] 
Antunes-Correa LM, Trevizan PF, Bacurau AVN, et al. Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure. J Cachexia Sarcopenia Muscle  2020; 11(1): 89-102.
[http://dx.doi.org/10.1002/jcsm.12495] [PMID: 31743617] 
[149] 
Chandrasekaran K, Muragundla A, Demarest TG, et al. mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy. Ann Clin Transl Neurol  2017; 4(12): 844-58.
[http://dx.doi.org/10.1002/acn3.484] [PMID: 29296613] 
[150] 
Pinti MV, Fink GK, Hathaway QA, Durr AJ, Kunovac A, Hollander JM. Mitochondrial dysfunction in type 2 diabetes mellitus: An organ-based analysis. Am J Physiol Endocrinol Metab  2019; 316(2): E268-85.
[http://dx.doi.org/10.1152/ajpendo.00314.2018] [PMID: 30601700] 
[151] 
Kotronen A, Seppälä-Lindroos A, Bergholm R, Yki-Järvinen H. Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome. Diabetologia  2008; 51(1): 130-8.
[http://dx.doi.org/10.1007/s00125-007-0867-x] [PMID: 18008059] 
[152] 
Koliaki C, Szendroedi J, Kaul K, et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab  2015; 21(5): 739-46.
[http://dx.doi.org/10.1016/j.cmet.2015.04.004] [PMID: 25955209] 
[153] 
Phielix E, Schrauwen-Hinderling VB, Mensink M, et al. Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes  2008; 57(11): 2943-9.
[http://dx.doi.org/10.2337/db08-0391] [PMID: 18678616] 
[154] 
Beaudoin MS, Perry CG, Arkell AM, et al. Impairments in mitochondrial palmitoyl-CoA respiratory kinetics that precede development of diabetic cardiomyopathy are prevented by resveratrol in ZDF rats. J Physiol  2014; 592(12): 2519-33.
[http://dx.doi.org/10.1113/jphysiol.2013.270538] [PMID: 24639481] 
[155] 
Chowdhury SK, Smith DR, Fernyhough P. The role of aberrant mitochondrial bioenergetics in diabetic neuropathy. Neurobiol Dis  2013; 51: 56-65.
[http://dx.doi.org/10.1016/j.nbd.2012.03.016] [PMID: 22446165] 
[156] 
López-Lluch G, Hunt N, Jones B, et al. Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA  2006; 103(6): 1768-73.
[http://dx.doi.org/10.1073/pnas.0510452103] [PMID: 16446459] 
[157] 
Rasbach KA, Schnellmann RG. Signaling of mitochondrial biogenesis following oxidant injury. J Biol Chem  2007; 282(4): 2355-62.
[http://dx.doi.org/10.1074/jbc.M608009200] [PMID: 17116659] 
[158] 
Pacifici F, Di Cola D, Pastore D, et al. Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis. Int J Mol Sci  2019; 20(19): E4748.
[http://dx.doi.org/10.3390/ijms20194748] [PMID: 31557786] 
[159] 
Choi J, Chandrasekaran K, Inoue T, Muragundla A, Russell JW. PGC-1α regulation of mitochondrial degeneration in experimental diabetic neuropathy. Neurobiol Dis  2014; 64: 118-30.
[http://dx.doi.org/10.1016/j.nbd.2014.01.001] [PMID: 24423644] 
[160] 
Chandrasekaran K, Salimian M, Konduru SR, et al. Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy. Brain  2019; 142(12): 3737-52.
[http://dx.doi.org/10.1093/brain/awz324] [PMID: 31754701] 
[161] 
Gliemann L, Nyberg M, Hellsten Y. Effects of exercise training and resveratrol on vascular health in aging. Free Radic Biol Med  2016; 98: 165-76.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.037] [PMID: 27085843] 
[162] 
Cao Y, Jiang X, Ma H, Wang Y, Xue P, Liu Y. SIRT1 and insulin resistance. J Diabetes Complications  2016; 30(1): 178-83.
[http://dx.doi.org/10.1016/j.jdiacomp.2015.08.022] [PMID: 26422395] 
[163] 
Ferrara N, Rinaldi B, Corbi G, et al. Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res  2008; 11(1): 139-50.
[http://dx.doi.org/10.1089/rej.2007.0576] [PMID: 18069916] 
[164] 
Radak Z, Suzuki K, Posa A, Petrovszky Z, Koltai E, Boldogh I. The systemic role of SIRT1 in exercise mediated adaptation. Redox Biol  2020; 35: 101467.
[http://dx.doi.org/10.1016/j.redox.2020.101467] [PMID: 32086007] 
[165] 
Brenmoehl J, Walz C, Renne U, et al. Metabolic adaptations in the liver of born long-distance running mice. Med Sci Sports Exerc  2013; 45(5): 841-50.
[http://dx.doi.org/10.1249/MSS.0b013e31827e0fca] [PMID: 23247708] 
[166] 
Gurd BJ, Perry CG, Heigenhauser GJ, Spriet LL, Bonen A. High-intensity interval training increases SIRT1 activity in human skeletal muscle. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme  2010; 35(3): 350-7.
[http://dx.doi.org/10.1139/H10-030] 
[167] 
Aditya R, Kiran AR, Varma DS, Vemuri R, Gundamaraju R. A Review on SIRtuins in Diabetes. Curr Pharm Des  2017; 23(16): 2299-307.
[http://dx.doi.org/10.2174/1381612823666170125153334] [PMID: 28128062] 
[168] 
Wall CE, Yu RT, Atkins AR, Downes M, Evans RM. Nuclear receptors and AMPK: can exercise mimetics cure diabetes? J Mol Endocrinol  2016; 57(1): R49-58.
[http://dx.doi.org/10.1530/JME-16-0073] [PMID: 27106806] 
[169] 
Lin J, Puigserver P, Donovan J, Tarr P, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem  2002; 277(3): 1645-8.
[http://dx.doi.org/10.1074/jbc.C100631200] [PMID: 11733490] 
[170] 
Short KR, Vittone JL, Bigelow ML, et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes  2003; 52(8): 1888-96.
[http://dx.doi.org/10.2337/diabetes.52.8.1888] [PMID: 12882902] 
[171] 
Cooper MA, Ryals JM, Wu PY, Wright KD, Walter KR, Wright DE. Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation. J Peripher Nerv Syst  2017; 22(1): 39-46.
[http://dx.doi.org/10.1111/jns.12199] [PMID: 27935216] 
[172] 
Cooper MA, Menta BW, Perez-Sanchez C, et al. A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice. Exp Neurol  2018; 306: 149-57.
[http://dx.doi.org/10.1016/j.expneurol.2018.05.011] [PMID: 29763602] 
[173] 
von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron  2012; 73(4): 638-52.
[http://dx.doi.org/10.1016/j.neuron.2012.02.008] [PMID: 22365541] 
[174] 
Campbell JNMR, Meyer RA. Mechanisms of neuropathic pain. Neuron  2006; 52(1): 77-92.
[http://dx.doi.org/10.1016/j.neuron.2006.09.021] [PMID: 17015228] 
[175] 
Costigan M, Scholz J, Woolf CJ. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu Rev Neurosci  2009; 32(1): 1-32.
[http://dx.doi.org/10.1146/annurev.neuro.051508.135531] [PMID: 19400724] 
[176] 
Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain  2006; 7(4): 281-9.
[http://dx.doi.org/10.1016/j.jpain.2005.11.008] [PMID: 16618472] 
[177] 
Ueda H. Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination. Mol Pain  2008; 4(11): 11.
[http://dx.doi.org/10.1186/1744-8069-4-11] [PMID: 18377664] 
[178] 
Chattopadhyay M, Zhou Z, Hao S, Mata M, Fink DJ. Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy. Mol Pain  2012; 8(1): 17.
[http://dx.doi.org/10.1186/1744-8069-8-17] [PMID: 22439790] 
[179] 
Aghdam AM, Shahabi P, Karimi-Sales E, et al. Swimming Exercise Induced Reversed Expression of miR-96 and Its Target Gene NaV1.3 in Diabetic Peripheral Neuropathy in Rats. Chin J Physiol  2018; 61(2): 124-9.
[http://dx.doi.org/10.4077/CJP.2018.BAG531] [PMID: 29689688] 
[180] 
Ma XQ, Qin J, Li HY, Yan XL, Zhao Y, Zhang LJ. Role of Exercise Activity in Alleviating Neuropathic Pain in DiabetesviaInhibition of the Pro-Inflammatory Signal Pathway. Biol Res Nurs  2019; 21(1): 14-21.
[http://dx.doi.org/10.1177/1099800418803175] [PMID: 30304943] 
[181] 
Chhaya SJ, Quiros-Molina D, Tamashiro-Orrego AD, Houlé JD, Detloff MR. Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury. J Neurotrauma  2019; 36(6): 877-90.
[http://dx.doi.org/10.1089/neu.2018.5819] [PMID: 30152715] 
[182] 
Liang L, Tao B, Fan L, Yaster M, Zhang Y, Tao YX. mTOR and its downstream pathway are activated in the dorsal root ganglion and spinal cord after peripheral inflammation, but not after nerve injury. Brain Res  2013; 1513: 17-25.
[http://dx.doi.org/10.1016/j.brainres.2013.04.003] [PMID: 23583278] 
[183] 
Ma X, Liu S, Liu D, Wang Q, Li H, Zhao Z. Exercise intervention attenuates neuropathic pain in diabetesviamechanisms of mammalian target of rapamycin (mTOR). Arch Physiol Biochem  2020; 126(1): 41-8.
[http://dx.doi.org/10.1080/13813455.2018.1489851] [PMID: 30317878] 
[184] 
McDaid EA, Monaghan B, Parker AI, Hayes JR, Allen JA. Peripheral autonomic impairment in patients newly diagnosed with type II diabetes. Diabetes Care  1994; 17(12): 1422-7.
[http://dx.doi.org/10.2337/diacare.17.12.1422] [PMID: 7882811] 
[185] 
Stevens MJ, Raffel DM, Allman KC, et al. Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation  1998; 98(10): 961-8.
[http://dx.doi.org/10.1161/01.CIR.98.10.961] [PMID: 9737515] 
[186] 
Pop-Busui R. Cardiac autonomic neuropathy in diabetes: A clinical perspective. Diabetes Care  2010; 33(2): 434-41.
[http://dx.doi.org/10.2337/dc09-1294] [PMID: 20103559] 
[187] 
Stables CL, Glasser RL, Feldman EL. Diabetic cardiac autonomic neuropathy: insights from animal models. Auton Neurosci  2013; 177(2): 74-80.
[http://dx.doi.org/10.1016/j.autneu.2013.03.001] [PMID: 23562143] 
[188] 
VanHoose L, Sawers Y, Loganathan R, et al. Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat. Cardiovasc Diabetol  2010; 9: 56.
[http://dx.doi.org/10.1186/1475-2840-9-56] [PMID: 20860788] 
[189] 
Lu B, Hu J, Wen J, et al. Determination of peripheral neuropathy prevalence and associated factors in Chinese subjects with diabetes and pre-diabetes - ShangHai Diabetic neuRopathy Epidemiology and Molecular Genetics Study (SH-DREAMS). PLoS One  2013; 8(4): e61053.
[http://dx.doi.org/10.1371/journal.pone.0061053] [PMID: 23613782] 
[190] 
Schlesinger S, Herder C, Kannenberg JM, et al. General and Abdominal Obesity and Incident Distal Sensorimotor Polyneuropathy: Insights Into Inflammatory Biomarkers as Potential Mediators in the KORA F4/FF4 Cohort. Diabetes Care  2019; 42(2): 240-7.
[http://dx.doi.org/10.2337/dc18-1842] [PMID: 30523031] 
[191] 
Andersen ST, Witte DR, Dalsgaard EM, et al. Risk Factors for Incident Diabetic Polyneuropathy in a Cohort With Screen-Detected Type 2 Diabetes Followed for 13 Years: ADDITION-Denmark. Diabetes Care  2018; 41(5): 1068-75.
[http://dx.doi.org/10.2337/dc17-2062] [PMID: 29487078] 
[192] 
Callaghan BC, Xia R, Reynolds E, et al. Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population. JAMA Neurol  2016; 73(12): 1468-76.
[http://dx.doi.org/10.1001/jamaneurol.2016.3745] [PMID: 27802497] 
[193] 
Callaghan BC, Gao L, Li Y, et al. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy. Ann Clin Transl Neurol  2018; 5(4): 397-405.
[http://dx.doi.org/10.1002/acn3.531] [PMID: 29687018] 
[194] 
Callaghan BC, Xia R, Banerjee M, et al. Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care  2016; 39(5): 801-7.
[http://dx.doi.org/10.2337/dc16-0081] [PMID: 26965720] 
[195] 
Hanewinckel R, Drenthen J, Ligthart S, et al. Metabolic syndrome is related to polyneuropathy and impaired peripheral nerve function: A prospective population-based cohort study. J Neurol Neurosurg Psychiatry  2016; 87(12): 1336-42.
[http://dx.doi.org/10.1136/jnnp-2016-314171] [PMID: 27656045] 
[196] 
Callaghan BC, Reynolds E, Banerjee M, Kerber KA, Skolarus LE, Burke JF. Longitudinal pattern of pain medication utilization in peripheral neuropathy patients. Pain 2018.
[PMID: 30418352] 
[197] 
Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care  2001; 24(8): 1448-53.
[http://dx.doi.org/10.2337/diacare.24.8.1448] [PMID: 11473085] 
[198] 
Novella SP, Inzucchi SE, Goldstein JM. The frequency of undiagnosed diabetes and impaired glucose tolerance in patients with idiopathic sensory neuropathy. Muscle Nerve  2001; 24(9): 1229-31.
[http://dx.doi.org/10.1002/mus.1137] [PMID: 11494278] 
[199] 
Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology  2003; 60(1): 108-11.
[http://dx.doi.org/10.1212/WNL.60.1.108] [PMID: 12525727] 
[200] 
Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care  1998; 21(4): 518-24.
[http://dx.doi.org/10.2337/diacare.21.4.518] [PMID: 9571335] 
[201] 
Bonadonna R, Cucinotta D, Fedele D, Riccardi G, Tiengo A, Tiengo A. The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care  2006; 29(12): 2701-7.
[http://dx.doi.org/10.2337/dc06-0942] [PMID: 17130208] 
[202] 
Ylitalo KR, Sowers M, Heeringa S. Peripheral vascular disease and peripheral neuropathy in individuals with cardiometabolic clustering and obesity: National Health and Nutrition Examination Survey 2001-2004. Diabetes Care  2011; 34(7): 1642-7.
[http://dx.doi.org/10.2337/dc10-2150] [PMID: 21593304] 
[203] 
Isomaa B, Henricsson M, Almgren P, Tuomi T, Taskinen MR, Groop L. The metabolic syndrome influences the risk of chronic complications in patients with type II diabetes. Diabetologia  2001; 44(9): 1148-54.
[http://dx.doi.org/10.1007/s001250100615] [PMID: 11596670] 
[204] 
Costa LA, Canani LH, Lisbôa HR, Tres GS, Gross JL. Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes. Diabet Med  2004; 21(3): 252-5.
[http://dx.doi.org/10.1111/j.1464-5491.2004.01124.x] [PMID: 15008835] 
[205] 
Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev  2012; 28(Suppl. 1): 8-14.
[http://dx.doi.org/10.1002/dmrr.2239] [PMID: 22271716] 
[206] 
Smith AG, Singleton JR. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. J Diabetes Complications  2013; 27(5): 436-42.
[http://dx.doi.org/10.1016/j.jdiacomp.2013.04.003] [PMID: 23731827] 
[207] 
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(10): 2619-25.
[http://dx.doi.org/10.2337/dc06-2479] [PMID: 17513707] 
[208] 
Cerletti P, Keidel D, Imboden M, Schindler C, Probst-Hensch N. The modifying role of physical activity in the cross-sectional and longitudinal association of health-related quality of life with physiological functioning-based latent classes and metabolic syndrome. Health Qual Life Outcomes  2020; 18(1): 345.
[http://dx.doi.org/10.1186/s12955-020-01557-z] [PMID: 33081800] 
[209] 
Davidson LE, Hudson R, Kilpatrick K, et al. Effects of exercise modality on insulin resistance and functional limitation in older adults: A randomized controlled trial. Arch Intern Med  2009; 169(2): 122-31.
[http://dx.doi.org/10.1001/archinternmed.2008.558] [PMID: 19171808] 
[210] 
Healy GN, Wijndaele K, Dunstan DW, et al. Objectively measured sedentary time, physical activity, and metabolic risk: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Diabetes Care  2008; 31(2): 369-71.
[http://dx.doi.org/10.2337/dc07-1795] [PMID: 18000181] 
[211] 
Myers J, Kokkinos P, Nyelin E. Physical Activity, Cardiorespiratory Fitness, and the Metabolic Syndrome. Nutrients  2019; 11(7): E1652.
[http://dx.doi.org/10.3390/nu11071652] [PMID: 31331009] 
[212] 
Larose J, Sigal RJ, Boulé NG, et al. Effect of exercise training on physical fitness in type II diabetes mellitus. Med Sci Sports Exerc  2010; 42(8): 1439-47.
[http://dx.doi.org/10.1249/MSS.0b013e3181d322dd] [PMID: 20639722] 
[213] 
Booth FW, Roberts CK, Thyfault JP, Ruegsegger GN, Toedebusch RG. Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms. Physiol Rev  2017; 97(4): 1351-402.
[http://dx.doi.org/10.1152/physrev.00019.2016] [PMID: 28814614] 
[214] 
Laaksonen DE, Lindström J, Lakka TA, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes  2005; 54(1): 158-65.
[http://dx.doi.org/10.2337/diabetes.54.1.158] [PMID: 15616024] 
[215] 
Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care  1997; 20(4): 537-44.
[http://dx.doi.org/10.2337/diacare.20.4.537] [PMID: 9096977] 
[216] 
Colberg SR. Key Points from the Updated Guidelines on Exercise and Diabetes. Front Endocrinol (Lausanne)  2017; 8(33): 33.
[http://dx.doi.org/10.3389/fendo.2017.00033] [PMID: 28265261] 
[217] 
Tucker PSF-WK, Fisher-Wellman K, Bloomer RJ. Can exercise minimize postprandial oxidative stress in patients with type 2 diabetes? Curr Diabetes Rev  2008; 4(4): 309-19.
[http://dx.doi.org/10.2174/157339908786241160] [PMID: 18991599] 
[218] 
Nimmo MA, Leggate M, Viana JL, King JA. The effect of physical activity on mediators of inflammation. Diabetes Obes Metab  2013; 15(s3)(Suppl. 3): 51-60.
[http://dx.doi.org/10.1111/dom.12156] [PMID: 24003921] 
[219] 
Roque FR, Hernanz R, Salaices M, Briones AM. Exercise training and cardiometabolic diseases: focus on the vascular system. Curr Hypertens Rep  2013; 15(3): 204-14.
[http://dx.doi.org/10.1007/s11906-013-0336-5] [PMID: 23519745] 
[220] 
Vinik EJ, Hayes RP, Oglesby A, et al. The development and validation of the Norfolk QOL-DN, a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther  2005; 7(3): 497-508.
[http://dx.doi.org/10.1089/dia.2005.7.497] [PMID: 15929681] 
[221] 
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(3): 218-27.
[http://dx.doi.org/10.1111/j.1529-8027.2008.00180.x] [PMID: 18844788] 
[222] 
Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care  1994; 17(11): 1281-9.
[http://dx.doi.org/10.2337/diacare.17.11.1281] [PMID: 7821168] 
[223] 
Streckmann F, Zopf EM, Lehmann HC, et al. Exercise intervention studies in patients with peripheral neuropathy: A systematic review. Sports Med  2014; 44(9): 1289-304.
[http://dx.doi.org/10.1007/s40279-014-0207-5] [PMID: 24927670] 
[224] 
Melese H, Alamer A, Hailu Temesgen M, Kahsay G. Effectiveness of Exercise Therapy on Gait Function in Diabetic Peripheral Neuropathy Patients: A Systematic Review of Randomized Controlled Trials. Diabetes Metab Syndr Obes  2020; 13: 2753-64.
[http://dx.doi.org/10.2147/DMSO.S261175] [PMID: 32848436] 
[225] 
Gu Y, Dennis SM, Kiernan MC, Harmer AR. Aerobic exercise training may improve nerve function in type 2 diabetes and pre-diabetes: A systematic review. Diabetes Metab Res Rev  2019; 35(2): e3099.
[PMID: 30462877] 
[226] 
Zilliox LA, Russell JW. Physical activity and dietary interventions in diabetic neuropathy: A systematic review. Clin Auton Res  2019; 29(4): 443-55.
[http://dx.doi.org/10.1007/s10286-019-00607-x] [PMID: 31076938] 
[227] 
Yoo M. Pilot Study of Exercise Therapy on Painful Diabetic Peripheral Neuropathy.Pain Med.  The Oxford University Press 2015; 16: pp. (8)1482-9.
[228] 
Jamal A, Ahmad I, Ahamed N, Azharuddin M, Alam F, Hussain ME. Whole body vibration showed beneficial effect on pain, balance measures and quality of life in painful diabetic peripheral neuropathy: A randomized controlled trial. J Diabetes Metab Disord  2019; 19(1): 61-9.
[http://dx.doi.org/10.1007/s40200-019-00476-1] [PMID: 32550157] 
[229] 
Dong Y, Wang W, Zheng J, Chen S, Qiao J, Wang X. Whole Body Vibration Exercise for Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Arch Phys Med Rehabil  2019; 100(11): 2167-78.
[http://dx.doi.org/10.1016/j.apmr.2019.03.011] [PMID: 31004565] 
[230] 
Gomes-Neto M, de Sá-Caputo DDC, Paineiras-Domingos LL, et al. Effects of Whole-Body Vibration in Older Adult Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Can J Diabetes  2019; 43(7): 524-529.e2.
[http://dx.doi.org/10.1016/j.jcjd.2019.03.008] [PMID: 31104903] 
[231] 
Kessler NJLM, Lockard MM, Fischer J. Whole body vibration improves symptoms of diabetic peripheral neuropathy. J Bodyw Mov Ther  2020; 24(2): 1-3.
[http://dx.doi.org/10.1016/j.jbmt.2020.01.004] [PMID: 32507132] 
[232] 
Ahn S, Song R. Effects of Tai Chi Exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy. J Altern Complement Med  2012; 18(12): 1172-8.
[http://dx.doi.org/10.1089/acm.2011.0690] [PMID: 22985218] 
[233] 
Dixit S, Maiya AG, Shastry BA. Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: A single blind, parallel group randomized controlled trial. J Diabetes Complications  2014; 28(3): 332-9.
[http://dx.doi.org/10.1016/j.jdiacomp.2013.12.006] [PMID: 24507164] 
[234] 
Balducci S, Iacobellis G, Parisi L, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications  2006; 20(4): 216-23.
[http://dx.doi.org/10.1016/j.jdiacomp.2005.07.005] [PMID: 16798472] 
[235] 
Gholami F, Nazari H, Alimi M. Cycle Training improves vascular function and neuropathic symptoms in patients with type 2 diabetes and peripheral neuropathy: A randomized controlled trial. Exp Gerontol  2020; 131: 110799.
[http://dx.doi.org/10.1016/j.exger.2019.110799] [PMID: 31899340] 
[236] 
Singleton JR, Smith AG, Marcus RL. Exercise as Therapy for Diabetic and Prediabetic Neuropathy. Curr Diab Rep  2015; 15(12): 120.
[http://dx.doi.org/10.1007/s11892-015-0682-6] [PMID: 26538074] 
[237] 
Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care  2006; 29(6): 1294-9.
[http://dx.doi.org/10.2337/dc06-0224] [PMID: 16732011] 
[238] 
Venkataraman K, Tai BC, Khoo EYH, et al. Short-term strength and balance training does not improve quality of life but improves functional status in individuals with diabetic peripheral neuropathy: A randomised controlled trial. Diabetologia  2019; 62(12): 2200-10.
[http://dx.doi.org/10.1007/s00125-019-04979-7] [PMID: 31468106] 
[239] 
Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care  2002; 25(12): 2165-71.
[http://dx.doi.org/10.2337/diacare.25.12.2165] [PMID: 12453955] 
[240] 
Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial. Ann Neurol  1995; 38(6): 869-80.
[http://dx.doi.org/10.1002/ana.410380607] [PMID: 8526459] 
[241] 
Albers JW, Herman WH, Pop-Busui R, et al. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes Care  2010; 33(5): 1090-6.
[http://dx.doi.org/10.2337/dc09-1941] [PMID: 20150297] 
[242] 
Look ARG. Effects of a long-term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2 diabetes: the Look AHEAD study. Diabetologia  2017; 60(6): 980-8.
[http://dx.doi.org/10.1007/s00125-017-4253-z] [PMID: 28349174] 
[243] 
Singleton JR, Marcus RL, Jackson JE, K Lessard M, Graham TE, Smith AG. Exercise increases cutaneous nerve density in diabetic patients without neuropathy. Ann Clin Transl Neurol  2014; 1(10): 844-9.
[http://dx.doi.org/10.1002/acn3.125] [PMID: 25493275] 
[244] 
Billinger SA, Sisante JV, Alqahtani AS, Pasnoor M, Kluding PM. Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy. Int J Neurosci  2017; 127(1): 80-5.
[http://dx.doi.org/10.3109/00207454.2016.1144056] [PMID: 26785723] 
[245] 
Gholami F, Nikookheslat S, Salekzamani Y, Boule N, Jafari A. Effect of aerobic training on nerve conduction in men with type 2 diabetes and peripheral neuropathy: A randomized controlled trial. Neurophysiol Clin  2018; 48(4): 195-202.
[http://dx.doi.org/10.1016/j.neucli.2018.03.001] [PMID: 29606547] 
[246] 
Fisher MA, Langbein WE, Collins EG, Williams K, Corzine L. Physiological improvement with moderate exercise in type II diabetic neuropathy. Electromyogr Clin Neurophysiol  2007; 47(1): 23-8.
[PMID: 17375878] 
[247] 
Hung JW, Liou CW, Wang PW, et al. Effect of 12-week tai chi chuan exercise on peripheral nerve modulation in patients with type 2 diabetes mellitus. J Rehabil Med  2009; 41(11): 924-9.
[http://dx.doi.org/10.2340/16501977-0445] [PMID: 19841845] 
[248] 
Stubbs EB Jr, Fisher MA, Miller CM, et al. Randomized Controlled Trial of Physical Exercise in Diabetic Veterans With Length-Dependent Distal Symmetric Polyneuropathy. Front Neurosci  2019; 13(51): 51.
[http://dx.doi.org/10.3389/fnins.2019.00051] [PMID: 30804739] 
[249] 
Schwartz AVVE, Vittinghoff E, Sellmeyer DE, et al. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care  2008; 31(3): 391-6.
[http://dx.doi.org/10.2337/dc07-1152] [PMID: 18056893] 
[250] 
Pijpers E, Ferreira I, de Jongh RT, et al. Older individuals with diabetes have an increased risk of recurrent falls: Analysis of potential mediating factors: the Longitudinal Ageing Study Amsterdam. Age Ageing  2012; 41(3): 358-65.
[http://dx.doi.org/10.1093/ageing/afr145] [PMID: 22156559] 
[251] 
Crews RT YS, Fleischer AE, Wu SC. A growing troubling triad: diabetes, aging, and falls. J Aging Res  2013; 2013
[252] 
Strotmeyer ES, de Rekeneire N, Schwartz AV, et al. The relationship of reduced peripheral nerve function and diabetes with physical performance in older white and black adults: the Health, Aging, and Body Composition (Health ABC) study. Diabetes Care  2008; 31(9): 1767-72.
[http://dx.doi.org/10.2337/dc08-0433] [PMID: 18535192] 
[253] 
Alsubiheen A, Petrofsky J, Yu W, Lee H. Effect of Tai Chi Combined with Mental Imagery on Cutaneous Microcirculatory Function and Blood Pressure in a Diabetic and Elderly Population. Healthcare (Basel)  2020; 8(3): 342.
[http://dx.doi.org/10.3390/healthcare8030342] [PMID: 32947783] 
[254] 
Quigley PABT, Bulat T, Schulz B, et al. Exercise interventions, gait, and balance in older subjects with distal symmetric polyneuropathy: A three-group randomized clinical trial. Am J Phys Med Rehabil  2014; 93(1): 1-12.
[http://dx.doi.org/10.1097/PHM.0000000000000052] [PMID: 24355993] 
[255] 
Morrison S, Colberg SR, Parson HK, Vinik AI. Exercise improves gait, reaction time and postural stability in older adults with type 2 diabetes and neuropathy. J Diabetes Complications  2014; 28(5): 715-22.
[http://dx.doi.org/10.1016/j.jdiacomp.2014.04.007] [PMID: 24929798] 
[256] 
Allet L, Armand S, de Bie RA, et al. The gait and balance of patients with diabetes can be improved: A randomised controlled trial. Diabetologia  2010; 53(3): 458-66.
[http://dx.doi.org/10.1007/s00125-009-1592-4] [PMID: 19921145] 
[257] 
Song CH, Petrofsky JS, Lee SW, Lee KJ, Yim JE. Effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies. Diabetes Technol Ther  2011; 13(8): 803-11.
[http://dx.doi.org/10.1089/dia.2011.0036] [PMID: 21561371] 
[258] 
Richardson JK, Sandman D, Vela S. A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. Arch Phys Med Rehabil  2001; 82(2): 205-9.
[http://dx.doi.org/10.1053/apmr.2001.19742] [PMID: 11239311] 
[259] 
Akbari M, Jafari H, Moshashaee A, Forugh B. Do diabetic neuropathy patients benefit from balance training? J Rehabil Res Dev  2012; 49(2): 333-8.
[http://dx.doi.org/10.1682/JRRD.2010.10.0197] [PMID: 22773533] 
[260] 
Rojhani-Shirazi Z, Barzintaj F, Salimifard MR. Comparison the effects of two types of therapeutic exercises Frenkele vs. Swiss ball on the clinical balance measures in patients with type II diabetic neuropathy. Diabetes Metab Syndr  2017; 11(Suppl. 1): S29-32.
[http://dx.doi.org/10.1016/j.dsx.2016.08.020] [PMID: 27720359] 
[261] 
Lee K, Lee S, Song C. Whole-body vibration training improves balance, muscle strength and glycosylated hemoglobin in elderly patients with diabetic neuropathy. Tohoku J Exp Med  2013; 231(4): 305-14.
[http://dx.doi.org/10.1620/tjem.231.305] [PMID: 24334483] 
[262] 
Gu Y, Dennis SM. Are falls prevention programs effective at reducing the risk factors for falls in people with type-2 diabetes mellitus and peripheral neuropathy: A systematic review with narrative synthesis. J Diabetes Complications  2017; 31(2): 504-16.
[http://dx.doi.org/10.1016/j.jdiacomp.2016.10.004] [PMID: 27825536] 
[263] 
Parasoglou P, Rao S, Slade JM. Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy. Clin Ther  2017; 39(6): 1085-103.
[http://dx.doi.org/10.1016/j.clinthera.2017.05.001] [PMID: 28571613] 
[264] 
Vinik AIET, Erbas T. Diabetic autonomic neuropathy. Handb Clin Neurol  2013; 117: 279-94.
[http://dx.doi.org/10.1016/B978-0-444-53491-0.00022-5] [PMID: 24095132] 
[265] 
Valensi P, Pariès J, Attali JR. Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications-the French multicenter study. Metabolism  2003; 52(7): 815-20.
[http://dx.doi.org/10.1016/S0026-0495(03)00095-7] [PMID: 12870154] 
[266] 
Low PAB-LL, Benrud-Larson LM, Sletten DM, et al. Autonomic symptoms and diabetic neuropathy: A population-based study. Diabetes Care  2004; 27(12): 2942-7.
[http://dx.doi.org/10.2337/diacare.27.12.2942] [PMID: 15562211] 
[267] 
Eleftheriadou A, Williams S, Nevitt S, et al. The prevalence of cardiac autonomic neuropathy in prediabetes: A systematic review. Diabetologia  2021; 64(2): 288-303.
[http://dx.doi.org/10.1007/s00125-020-05316-z] [PMID: 33164108] 
[268] 
Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes  2014; 5(1): 17-39.
[http://dx.doi.org/10.4239/wjd.v5.i1.17] [PMID: 24567799] 
[269] 
Lièvre MMMP, Moulin P, Thivolet C, et al. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening. Trials  2011; 12(23): 23.
[http://dx.doi.org/10.1186/1745-6215-12-23] [PMID: 21269454] 
[270] 
Wackers FJYL, Young LH, Inzucchi SE, et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care  2004; 27(8): 1954-61.
[http://dx.doi.org/10.2337/diacare.27.8.1954] [PMID: 15277423] 
[271] 
Carnethon MRPR, Prineas RJ, Temprosa M, Zhang ZM, Uwaifo G, Molitch ME. The association among autonomic nervous system function, incident diabetes, and intervention arm in the Diabetes Prevention Program. Diabetes Care  2006; 29(4): 914-9.
[http://dx.doi.org/10.2337/diacare.29.04.06.dc05-1729] [PMID: 16567837] 
[272] 
Voulgari C, Pagoni S, Vinik A, Poirier P. Exercise improves cardiac autonomic function in obesity and diabetes. Metabolism  2013; 62(5): 609-21.
[http://dx.doi.org/10.1016/j.metabol.2012.09.005] [PMID: 23084034] 
[273] 
Buse JBGH, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: A scientific statement from the American Heart Association and the American Diabetes Association. Circulation  2007; 115(1): 114-26.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.179294] [PMID: 17192512] 
[274] 
Cerqueira É, Marinho DA, Neiva HP, Lourenço O. Inflammatory Effects of High and Moderate Intensity Exercise-A Systematic Review. Front Physiol  2020; 10(1550): 1550.
[http://dx.doi.org/10.3389/fphys.2019.01550] [PMID: 31992987] 
[275] 
Polydefkis M, Hauer P, Griffin JW, McArthur JC. Skin biopsy as a tool to assess distal small fiber innervation in diabetic neuropathy. Diabetes Technol Ther  2001; 3(1): 23-8.
[http://dx.doi.org/10.1089/152091501750219994] [PMID: 11469706] 
[276] 
Polydefkis M, Sirdofsky M, Hauer P, Petty BG, Murinson B, McArthur JC. Factors influencing nerve regeneration in a trial of timcodar dimesylate. Neurology  2006; 66(2): 259-61.
[http://dx.doi.org/10.1212/01.wnl.0000194209.37604.57] [PMID: 16434669] 
[277] 
Schiffmann R, Hauer P, Freeman B, et al. Enzyme replacement therapy and intraepidermal innervation density in Fabry disease. Muscle Nerve  2006; 34(1): 53-6.
[http://dx.doi.org/10.1002/mus.20550] [PMID: 16583374] 
[278] 
Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain  2004; 127(Pt 7): 1606-15.
[http://dx.doi.org/10.1093/brain/awh175] [PMID: 15128618] 
[279] 
Johnson CE, Takemoto JK. A Review of Beneficial Low-Intensity Exercises in Diabetic Peripheral Neuropathy Patients. J Pharm Pharm Sci  2019; 22(1): 22-7.
[http://dx.doi.org/10.18433/jpps30151] [PMID: 30599819] 
[280] 
President’s Council on Sports FN. Physical Activity Guidelines for Americans 2017.  Available from:https://www.hhs.gov/fitness/be-active/physicalactivty- guidelines-for-americans/index.html
[281] 
Donnelly JEGJ, Greene JL, Gibson CA, et al. Physical Activity Across the Curriculum (PAAC): A randomized controlled trial to promote physical activity and diminish overweight and obesity in elementary school children. Prev Med  2009; 49(4): 336-41.
[http://dx.doi.org/10.1016/j.ypmed.2009.07.022] [PMID: 19665037] 
[282] 
Praet SF, van Loon LJ. Exercise: the brittle cornerstone of type 2 diabetes treatment. Diabetologia  2008; 51(3): 398-401.
[http://dx.doi.org/10.1007/s00125-007-0910-y] [PMID: 18183362] 
[283] 
Tremblay MS LA, Carson V, Choquette L, et al. Canadian Sedentary Behaviour Guidelines for the Early Years (aged 0-4 years). Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme  2012; 37(2): 370-91.
[284] 
Koster A, Caserotti P, Patel KV, et al. Association of sedentary time with mortality independent of moderate to vigorous physical activity. PLoS One  2012; 7(6): e37696.
[http://dx.doi.org/10.1371/journal.pone.0037696] [PMID: 22719846] 
[285] 
Bey L, Hamilton MT. Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: A molecular reason to maintain daily low-intensity activity. J Physiol  2003; 551(Pt 2): 673-82.
[http://dx.doi.org/10.1113/jphysiol.2003.045591] [PMID: 12815182] 
[286] 
Hamilton MT, Hamilton DG, Zderic TW. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes  2007; 56(11): 2655-67.
[http://dx.doi.org/10.2337/db07-0882] [PMID: 17827399] 
[287] 
Harrison M, O’Gorman DJ, McCaffrey N, et al. Influence of acute exercise with and without carbohydrate replacement on postprandial lipid metabolism. J Appl Physiol  2009; 106(3): 943-9.
[http://dx.doi.org/10.1152/japplphysiol.91367.2008] [PMID: 19112157] 
[288] 
Stephens BRGK, Granados K, Zderic TW, Hamilton MT, Braun B. Effects of 1 day of inactivity on insulin action in healthy men and women: interaction with energy intake. Metabolism  2011; 60(7): 941-9.
[http://dx.doi.org/10.1016/j.metabol.2010.08.014] [PMID: 21067784] 
[289] 
Alicia A, Thorp P. Neville Owen, PhD, Maike Neuhaus, MS, David W. Dunstan, PhD. Sedentary Behaviors and Subsequent Health Outcomes in Adults A Systematic Review of Longitudinal Studies, 1996 –2011. Am J Prev Med  2011; 41(2): 207-15.
[PMID: 21767729] 
[290] 
Duvivier BMSN, Schaper NC, Bremers MA, et al. Minimal intensity physical activity (standing and walking) of longer duration improves insulin action and plasma lipids more than shorter periods of moderate to vigorous exercise (cycling) in sedentary subjects when energy expenditure is comparable. PLoS One  2013; 8(2): e55542.
[http://dx.doi.org/10.1371/journal.pone.0055542] [PMID: 23418444] 
[291] 
Swartz AMSL, Squires L, Strath SJ. Energy expenditure of interruptions to sedentary behavior. Int J Behav Nutr Phys Act  2011; 8(69): 69.
[http://dx.doi.org/10.1186/1479-5868-8-69] [PMID: 21708007] 
[292] 
Nygaard H TS, Høstmark AT. Slow postmeal walking reduces postprandial glycemia in middle-aged women. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme  2009; 34(6): 1087-92.
[http://dx.doi.org/10.1139/H09-110] 
[293] 
Dunstan DWKB, Kingwell BA, Larsen R, et al. Breaking up prolonged sitting reduces postprandial glucose and insulin responses. Diabetes Care  2012; 35(5): 976-83.
[http://dx.doi.org/10.2337/dc11-1931] [PMID: 22374636] 
[294] 
Cooper ARSS, Sebire S, Montgomery AA, et al. Sedentary time, breaks in sedentary time and metabolic variables in people with newly diagnosed type 2 diabetes. Diabetologia  2012; 55(3): 589-99.
[http://dx.doi.org/10.1007/s00125-011-2408-x] [PMID: 22167127] 
[295] 
Riebe D, Franklin BA, Thompson PD, et al. Updating ACSM’s Recommendations for Exercise Preparticipation Health Screening. Med Sci Sports Exerc  2015; 47(11): 2473-9.
[http://dx.doi.org/10.1249/MSS.0000000000000664] [PMID: 26473759] 
[296] 
Kruse RL, Lemaster JW, Madsen RW. Fall and balance outcomes after an intervention to promote leg strength, balance, and walking in people with diabetic peripheral neuropathy: “feet first” randomized controlled trial. Phys Ther  2010; 90(11): 1568-79.
[http://dx.doi.org/10.2522/ptj.20090362] [PMID: 20798179] 
[297] 
Mueller MJ, Tuttle LJ, Lemaster JW, et al. Weight-bearing versus nonweight-bearing exercise for persons with diabetes and peripheral neuropathy: A randomized controlled trial. Arch Phys Med Rehabil  2013; 94(5): 829-38.
[http://dx.doi.org/10.1016/j.apmr.2012.12.015] [PMID: 23276801] 
[298] 
Lemaster JWMM, Mueller MJ, Reiber GE, Mehr DR, Madsen RW, Conn VS. Effect of weight-bearing activity on foot ulcer incidence in people with diabetic peripheral neuropathy: feet first randomized controlled trial. Phys Ther  2008; 88(11): 1385-98.
[http://dx.doi.org/10.2522/ptj.20080019] [PMID: 18801859] 
[299] 
Kluding PMPM, Pasnoor M, Singh R, et al. Safety of aerobic exercise in people with diabetic peripheral neuropathy: single-group clinical trial. Phys Ther  2015; 95(2): 223-34.
[http://dx.doi.org/10.2522/ptj.20140108] [PMID: 25278335] 
[300] 
Piercy KLTR, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA  2018; 320(19): 2020-8.
[http://dx.doi.org/10.1001/jama.2018.14854] [PMID: 30418471] 
[301] 
Katzmarzyk PT, Powell KE, Jakicic JM, Troiano RP, Piercy K, Tennant B. Sedentary Behavior and Health: Update from the 2018 Physical Activity Guidelines Advisory Committee. Med Sci Sports Exerc  2019; 51(6): 1227-41.
[http://dx.doi.org/10.1249/MSS.0000000000001935] [PMID: 31095080] 
[302] 
Kluding PM, Bareiss SK, Hastings M, Marcus RL, Sinacore DR, Mueller MJ. Physical Training and Activity in People With Diabetic Peripheral Neuropathy: Paradigm Shift. Phys Ther  2017; 97(1): 31-43.
[PMID: 27445060] 
[303] 
Wilmot EG, Edwardson CL, Achana FA, et al. Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis. Diabetologia  2012; 55(11): 2895-905.
[http://dx.doi.org/10.1007/s00125-012-2677-z] [PMID: 22890825] 
[304] 
Edwardson CLGT, Gorely T, Davies MJ, et al. Association of sedentary behaviour with metabolic syndrome: A meta-analysis. PLoS One  2012; 7(4): e34916.
[http://dx.doi.org/10.1371/journal.pone.0034916] [PMID: 22514690] 
[305] 
van der Velde JHPM, Schaper NC, Stehouwer CDA, et al. Which is more important for cardiometabolic health: sedentary time, higher intensity physical activity or cardiorespiratory fitness? The Maastricht Study. Diabetologia  2018; 61(12): 2561-9.
[http://dx.doi.org/10.1007/s00125-018-4719-7] [PMID: 30198051] 
[306] 
Kozey Keadle S LK, Staudenmayer J, et al. he independent and combined effects of exercise training and reducing sedentary behavior on cardiometabolic risk factors. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme  2014; 39(7): 770-80.
[http://dx.doi.org/10.1139/apnm-2013-0379] 
[307] 
Gardiner PA, Eakin EG, Healy GN, Owen N. Feasibility of reducing older adults’ sedentary time. Am J Prev Med  2011; 41(2): 174-7.
[http://dx.doi.org/10.1016/j.amepre.2011.03.020] [PMID: 21767725] 
[308] 
Albers JW, Chaudhry V, Cavaletti G, Donehower RC. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database Syst Rev  2014; (3): CD005228.
[http://dx.doi.org/10.1002/14651858.CD005228.pub4] [PMID: 24687190] 
[309] 
Kadoglou NPE, Moustardas P, Kapelouzou A, et al. The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis. Eur J Histochem  2013; 57(1): e3.
[http://dx.doi.org/10.4081/ejh.2013.e3] [PMID: 23549462] 
[310] 
Hamed NSRN. Effect of high intensity interval training on diabetic obese women with polyneuropathy: A randomized controlled clinical trial. Phys Ther Rehabil 2014.
[http://dx.doi.org/10.7243/2055-2386-1-4] 
[311] 
Taveggia G, Villafañe JH, Vavassori F, Lecchi C, Borboni A, Negrini S. Multimodal treatment of distal sensorimotor polyneuropathy in diabetic patients: A randomized clinical trial. J Manipulative Physiol Ther  2014; 37(4): 242-52.
[http://dx.doi.org/10.1016/j.jmpt.2013.09.007] [PMID: 24656867] 
[312] 
Salsabili H, Bahrpeyma F, Esteki A. The effects of Task-Oriented Motor Training on gait characteristics of patients with type 2 diabetes neuropathy. J Diabetes Metab Disord  2016; 15: 14.
[http://dx.doi.org/10.1186/s40200-016-0236-8] [PMID: 27231683] 
[313] 
Ahmad I, Noohu MM, Verma S, Singla D, Hussain ME. Effect of sensorimotor training on balance measures and proprioception among middle and older age adults with diabetic peripheral neuropathy. Gait Posture  2019; 74: 114-20.
[http://dx.doi.org/10.1016/j.gaitpost.2019.08.018] [PMID: 31499405] 
[314] 
Cox ER, Gajanand T, Burton NW, Coombes JS, Coombes BK. Effect of different exercise training intensities on musculoskeletal and neuropathic pain in inactive individuals with type 2 diabetes - Preliminary randomised controlled trial. Diabetes Res Clin Pract  2020; 164: 108168.
[http://dx.doi.org/10.1016/j.diabres.2020.108168] [PMID: 32360399] 
Rights & Permissions Print Cite
Article Metrics
31
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1573399817666210923125832	Print ISSN 1573-3998
Publisher Name Bentham Science Publisher	Online ISSN 1875-6417
Current Diabetes Reviews

Exercise as Treatment for Neuropathy in the Setting of Diabetes and Prediabetic Metabolic Syndrome: A Review of Animal Models and Human Trials

Abstract

Related Journals

Related Books

Related Articles
