Current Diabetes Reports

, 15:120 | Cite as

Exercise as Therapy for Diabetic and Prediabetic Neuropathy

  • J. Robinson SingletonEmail author
  • A. Gordon Smith
  • Robin L. Marcus
Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Microvascular Complications—Neuropathy


Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function.


Diabetic neuropathy Exercise Metabolic syndrome Human trials Sedentary behavior Actigraphy 



All authors of this paper have funding from NIH that is supporting this work (NIH R01 DK064814).

Compliance with Ethics Guidelines

Conflict of Interest

J. Robinson Singleton, A. Gordon Smith, and Robin L. Marcus declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Dyck PJ, Kratz JM, Karnes JL, et al. 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. 1993;43:817–24.CrossRefPubMedGoogle Scholar
  2. 2.
    Pop-Busui R, Lu J, Lopes N, et al. Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort. J Peripher Nerv Syst. 2009;14:1–13.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Gordois A, Scuffham P, Shearer A, et al. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003;26:1790–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Guy RJ, Clark CA, Malcolm PN, et al. Evaluation of thermal and vibration sensation in diabetic neuropathy. Diabetologia. 1985;28:131–7.PubMedGoogle Scholar
  5. 5.
    Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997;46 Suppl 2:S54–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Kennedy JM, Zochodne DW. Experimental diabetic neuropathy with spontaneous recovery: is there irreparable damage? Diabetes. 2005;54:830–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Griffin JW, Thompson WJ. Biology and pathology of nonmyelinating Schwann cells. Glia. 2008;56:1518–31.CrossRefPubMedGoogle Scholar
  8. 8.
    Smith AG, Howard JR, Kroll R, et al. The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci. 2005;228:65–9.CrossRefPubMedGoogle Scholar
  9. 9.
    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;15:202–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Lauria G, Hsieh ST, Johansson O, et al. 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. 2010;17:903–12. e944-909.CrossRefPubMedGoogle Scholar
  11. 11.
    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;30:2619–25.CrossRefPubMedGoogle Scholar
  12. 12.
    Costa LA, Canani LH, Lisboa HR, et al. Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in type 2 diabetes. Diabet Med. 2004;21:252–5.CrossRefPubMedGoogle Scholar
  13. 13.•
    Smith AG, Singleton JR. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. J Diabetes Complicat. 2013;27:436–42. This study demonstrates the epidemiological link between nonglycemic features of metabolic syndrome and diabetic neuropathy.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia. 1996;39:1377–84.CrossRefPubMedGoogle Scholar
  15. 15.
    Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383–93.CrossRefPubMedGoogle Scholar
  16. 16.
    Straub RH, Thum M, Hollerbach C, et al. Impact of obesity on neuropathic late complications in NIDDM. Diabetes Care. 1994;17:1290–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Tesfaye S, Selvarajah D. The Eurodiab Study: what has this taught us about diabetic peripheral neuropathy? Curr Diab Rep. 2009;9:432–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Callaghan B, Feldman E. The metabolic syndrome and neuropathy: therapeutic challenges and opportunities. Ann Neurol. 2013;74:397–403.CrossRefPubMedGoogle Scholar
  19. 19.
    Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics. 2009;6:638–47.CrossRefPubMedGoogle Scholar
  20. 20.
    Watcho P, Stavniichuk R, Ribnicky DM, et al. High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L. Mediat Inflamm. 2010;2010:268547.CrossRefGoogle Scholar
  21. 21.
    Davidson EP, Coppey LJ, Calcutt NA, et al. Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction. Diabetes Metab Res Rev. 2010;26:306–18.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    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;52:1255–63.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.•
    Groover AL, Ryals JM, Guilford BL, et al. Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice. Pain. 2013;154:2658–67. Behavioral therapy improves indices of neuropathic pain in a mouse model of prediabetic neuropathy.CrossRefPubMedGoogle Scholar
  24. 24.
    Vincent AM, Hayes JM, McLean LL, et al. Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes. 2009;58:2376–85.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    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.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Singleton JR, Smith AG, Russell JW, et al. Microvascular complications of impaired glucose tolerance. Diabetes. 2003;52:2867–73.CrossRefPubMedGoogle Scholar
  27. 27.
    Lewis GF, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002;23:201–29.CrossRefPubMedGoogle Scholar
  28. 28.
    Oltman CL, Coppey LJ, Gellett JS, et al. Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats. Am J Physiol Endocrinol Metab. 2005;289:E113–22.CrossRefPubMedGoogle Scholar
  29. 29.
    Obrosova IG, Drel VR, Oltman CL, et al. Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats. Am J Physiol Endocrinol Metab. 2007;293:E1645–55.CrossRefPubMedGoogle Scholar
  30. 30.
    Esenabhalu VE, Schaeffer G, Graier WF. Free fatty acid overload attenuates Ca(2+) signaling and NO production in endothelial cells. Antioxid Redox Signal. 2003;5:147–53.CrossRefPubMedGoogle Scholar
  31. 31.
    Pleiner J, Schaller G, Mittermayer F, et al. FFA-induced endothelial dysfunction can be corrected by vitamin C. J Clin Endocrinol Metab. 2002;87:2913–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Vincent AM, McLean LL, Backus C, et al. Short-term hyperglycemia produces oxidative damage and apoptosis in neurons. FASEB J. 2005;19:638–40.PubMedGoogle Scholar
  33. 33.
    Ahmed FN, Naqvi FN, Shafiq F. Lipid peroxidation and serum antioxidant enzymes in patients with type 2 diabetes mellitus. Ann N Y Acad Sci. 2006;1084:481–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Cruz NG, Sousa LP, Sousa MO, et al. The linkage between inflammation and type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;99:85–92.CrossRefPubMedGoogle Scholar
  35. 35.
    Boyanovsky B, Karakashian A, King K, et al. Uptake and metabolism of low density lipoproteins with elevated ceramide content by human microvascular endothelial cells: implications for the regulation of apoptosis. J Biol Chem. 2003;278:26992–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Cheng HT, Dauch JR, Hayes JM, et al. Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes. Neurobiol Dis. 2012;45:280–7.PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Casanova-Molla J, Morales M, Planas-Rigol E, et al. Epidermal Langerhans cells in small fiber neuropathies. Pain. 2012;153:982–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Dauch JR, Bender DE, Luna-Wong LA, et al. Neurogenic factor-induced Langerhans cell activation in diabetic mice with mechanical allodynia. J Neuroinflammation. 2013;10:64.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995;122:561.CrossRefGoogle Scholar
  40. 40.
    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;376:419–30.PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Callaghan BC, Little A, Feldman E, et al. Enhanced glycemic control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012; in press.Google Scholar
  42. 42.
    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;124:2448–58.CrossRefPubMedGoogle Scholar
  43. 43.
    Krentz AJ, Honigsberger L, Ellis SH, et al. A 12-month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy. Diabet Med. 1992;9:463–8.CrossRefPubMedGoogle Scholar
  44. 44.
    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;55:341–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Malik R, Williamson S, Abbott C. Effect of the angiotensin converting enzyme inhibitor trandoalapril on human diabetic neuropathy: a randomised controlled trial. Lancet. 1998;352:1978–81.CrossRefPubMedGoogle Scholar
  46. 46.
    Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997;46:S62–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004;21:114–21.CrossRefPubMedGoogle Scholar
  48. 48.
    Cameron N, Tuck S, McCabe L, et al. Effects of the hydroxyl radical scavenger, dimethylthiorurea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes. Diabetologia. 2001;44:1161–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Greene DA, Arezzo JC, Brown MB. Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group. Neurology. 1999;53:580–91.CrossRefPubMedGoogle Scholar
  50. 50.
    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;310:81–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Pfeifer MA, Schumer MP. Clinical trials of diabetic neuropathy: past present and future. Diabetes. 1995;44:1355–61.CrossRefPubMedGoogle Scholar
  52. 52.
    Mojaddidi M, Quattrini C, Tavakoli M, et al. Recent developments in the assessment of efficacy in clinical trials of diabetic neuropathy. Curr Diab Rep. 2005;5:417–22.CrossRefPubMedGoogle Scholar
  53. 53.
    Malik RA, Tesfaye S, Newrick PG, et al. Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia. 2005;48:578–85.CrossRefPubMedGoogle Scholar
  54. 54.
    Simone DA, Nolano M, Johnson T, et al. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998;18:8947–59.PubMedGoogle Scholar
  55. 55.
    Polydefkis M, Hauer P, Sheth S, et al. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain. 2004;127:1606–15.CrossRefPubMedGoogle Scholar
  56. 56.•
    Singleton JR, Marcus RL, Lessard MK, et al. Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients. Ann Neurol. 2015;77:146–53. Exercise alters the biology of cutaneous nociceptive fibers in the absence of neuropathy disease state.CrossRefPubMedGoogle Scholar
  57. 57.
    Huang HH, Farmer K, Windscheffel J, et al. Exercise increases insulin content and basal secretion in pancreatic islets in type 1 diabetic mice. Exp Diabetes Res. 2011;2011:481427.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Kiraly MA, Bates HE, Yue JT, et al. Attenuation of type 2 diabetes mellitus in the male Zucker diabetic fatty rat: the effects of stress and non-volitional exercise. Metabolism. 2007;56:732–44.CrossRefPubMedGoogle Scholar
  59. 59.
    Chen YW, Li YT, Chen YC, et al. Exercise training attenuates neuropathic pain and cytokine expression after chronic constriction injury of rat sciatic nerve. Anesth Analg. 2012;114:1330–7.CrossRefPubMedGoogle Scholar
  60. 60.
    Sharma NK, Ryals JM, Gajewski BJ, et al. Aerobic exercise alters analgesia and neurotrophin-3 synthesis in an animal model of chronic widespread pain. Phys Ther. 2010;90:714–25.PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Selagzi H, Buyukakilli B, Cimen B, et al. Protective and therapeutic effects of swimming exercise training on diabetic peripheral neuropathy of streptozotocin-induced diabetic rats. J Endocrinol Investig. 2008;31:971–8.CrossRefGoogle Scholar
  62. 62.
    Orchard TJ, Temprosa M, Goldberg R, et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005;142:611–9.PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    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;346:393–403.CrossRefPubMedGoogle Scholar
  64. 64.
    Tuomilehto J, Del Prato S. Mealtime glucose regulation in type 2 diabetes. Int J Clin Pract. 2001;55:380–3.PubMedGoogle Scholar
  65. 65.•
    Balducci S, Iacobellis G, Parisi L, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat. 2006;20:216–23. First study to show effect of exercise on diabetic neuropathy prevention.CrossRefPubMedGoogle Scholar
  66. 66.
    Singleton JR, Marcus RL, Jackson JE, et al. Exercise increases cutaneous nerve density in diabetic patients without neuropathy. Ann Clin Transl Neurol. 2014;1:844–9.PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    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;53:458–66.PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    The Expert Panel on Detection and Treatment of High Blood Cholesterol in Adults, The Third Report of the ATP III. NIH publication 01-3670., Bethesda Maryland: National Institutes of Health National Heart Lung and Blood Institute.
  69. 69.
    Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006;29:1294–9.CrossRefPubMedGoogle Scholar
  70. 70.•
    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 Complicat. 2012. First human study to demonstrate improvement in diabetic neuropathy indices with exercise. Google Scholar
  71. 71.
    Kluding PM, Pasnoor M, Singh R, et al. Safety of aerobic exercise in people with diabetic peripheral neuropathy: single-group clinical trial. Phys Ther. 2015;95:223–34.CrossRefPubMedGoogle Scholar
  72. 72.
    Yoo M, D’Silva LJ, Martin K, et al. Pilot study of exercise therapy on painful diabetic peripheral neuropathy. Pain Med. 2015;16:1482–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Morrison S, Colberg SR, Parson HK, et al. Exercise improves gait, reaction time and postural stability in older adults with type 2 diabetes and neuropathy. J Diabetes Complicat. 2014;28:715–22.CrossRefPubMedGoogle Scholar
  74. 74.•
    Handsaker JC, Brown SJ, Bowling FL, et al. Contributory factors to unsteadiness during walking up and down stairs in patients with diabetic peripheral neuropathy. Diabetes Care. 2014;37:3047–53. Careful study of physical contributors to altered balance in diabetic neuropathy.CrossRefPubMedGoogle Scholar
  75. 75.
    Handsaker JC, Brown SJ, Bowling FL, et al. Resistance exercise training increases lower limb speed of strength generation during stair ascent and descent in people with diabetic peripheral neuropathy. Diabet Med. 2015. doi: 10.1111/dme.12841.Google Scholar
  76. 76.
    Streckmann F, Zopf EM, Lehmann HC, et al. Exercise intervention studies in patients with peripheral neuropathy: a systematic review. Sports Med. 2014;44:1289–304.CrossRefPubMedGoogle Scholar
  77. 77.
    Lemaster JW, Mueller MJ, Reiber GE, et al. Effect of weight-bearing activity on foot ulcer incidence in people with diabetic peripheral neuropathy: feet first randomized controlled trial. Phys Ther. 2008;88:1385–98.CrossRefPubMedGoogle Scholar
  78. 78.
    Armstrong DG, Lavery LA, Holtz-Neiderer K, et al. Variability in activity may precede diabetic foot ulceration. Diabetes Care. 2004;27:1980–4.CrossRefPubMedGoogle Scholar
  79. 79.
    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;90:1568–79.CrossRefPubMedGoogle Scholar
  80. 80.
    Donnelly JE, Blair SN, Jakicic JM, et al. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41:459–71.CrossRefPubMedGoogle Scholar
  81. 81.
    Praet SF, van Rooij ES, Wijtvliet A, et al. Brisk walking compared with an individualised medical fitness programme for patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2008;51:736–46.PubMedCentralCrossRefPubMedGoogle Scholar
  82. 82.
    Tremblay M, Sedentary Behaviour Research N. Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”. Appl Physiol Nutr Metab. 2012;37:540–2.CrossRefGoogle Scholar
  83. 83.
    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, e37696.PubMedCentralCrossRefPubMedGoogle Scholar
  84. 84.
    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;551:673–82.PubMedCentralCrossRefPubMedGoogle Scholar
  85. 85.
    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;56:2655–67.CrossRefPubMedGoogle Scholar
  86. 86.
    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 (1985). 2009;106:943–9.CrossRefGoogle Scholar
  87. 87.
    Stephens BR, Granados K, Zderic TW, et al. Effects of 1 day of inactivity on insulin action in healthy men and women: interaction with energy intake. Metabolism. 2011;60:941–9.CrossRefPubMedGoogle Scholar
  88. 88.
    Thorp AA, Owen N, Neuhaus M, et al. Sedentary behaviors and subsequent health outcomes in adults a systematic review of longitudinal studies, 1996-2011. Am J Prev Med. 2011;41:207–15.CrossRefPubMedGoogle Scholar
  89. 89.
    Duvivier BM, 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, e55542.PubMedCentralCrossRefPubMedGoogle Scholar
  90. 90.
    Swartz AM, Squires L, Strath SJ. Energy expenditure of interruptions to sedentary behavior. Int J Behav Nutr Phys Act. 2011;8:69.PubMedCentralCrossRefPubMedGoogle Scholar
  91. 91.
    Nygaard H, Tomten SE, Hostmark AT. Slow postmeal walking reduces postprandial glycemia in middle-aged women. Appl Physiol Nutr Metab. 2009;34:1087–92.CrossRefPubMedGoogle Scholar
  92. 92.
    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;31:369–71.CrossRefPubMedGoogle Scholar
  93. 93.
    Dunstan DW, Kingwell BA, Larsen R, et al. Breaking up prolonged sitting reduces postprandial glucose and insulin responses. Diabetes Care. 2012;35:976–83.PubMedCentralCrossRefPubMedGoogle Scholar
  94. 94.
    Cooper JN, Columbus ML, Shields KJ, et al. Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults. Metabolism. 2012;61:1589–97.PubMedCentralCrossRefPubMedGoogle Scholar
  95. 95.
    Gardiner PA, Eakin EG, Healy GN, et al. Feasibility of reducing older adults’ sedentary time. Am J Prev Med. 2011;41:174–7.CrossRefPubMedGoogle Scholar
  96. 96.
    De Greef KP, Deforche BI, Ruige JB, et al. The effects of a pedometer-based behavioral modification program with telephone support on physical activity and sedentary behavior in type 2 diabetes patients. Patient Educ Couns. 2011;84:275–9.CrossRefPubMedGoogle Scholar
  97. 97.
    Lyden K, Kozey Keadle SL, Staudenmayer JW, et al. Validity of two wearable monitors to estimate breaks from sedentary time. Med Sci Sports Exerc. 2012;44:2243–52.PubMedCentralCrossRefPubMedGoogle Scholar
  98. 98.
    Kozey-Keadle S, Libertine A, Lyden K, et al. Validation of wearable monitors for assessing sedentary behavior. Med Sci Sports Exerc. 2011;43:1561–7.CrossRefPubMedGoogle Scholar
  99. 99.
    Kozey-Keadle S, Libertine A, Staudenmayer J, et al. The feasibility of reducing and measuring sedentary time among overweight, non-exercising office workers. J Obes 2012; 2012: 282303.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • J. Robinson Singleton
    • 1
    Email author
  • A. Gordon Smith
    • 1
  • Robin L. Marcus
    • 2
  1. 1.Department of NeurologyUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Physical TherapyUniversity of UtahSalt Lake CityUSA

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