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The Effects of Exercise Training on the Brain-Derived Neurotrophic Factor (BDNF) in the Patients with Type 2 Diabetes: A Systematic Review of the Randomized Controlled Trials

Abstract

Purpose

Glucose dysregulation is one of the distinctive features of type 2 diabetes that is associated with an increased risk of cognitive impairment and dementia. The low concentrations of brain-derived neurotrophic factor (BDNF) are reported in people with insulin resistance, metabolic syndrome, and type 2 diabetes. BDNF can be increased by an adjustment in lifestyle including caloric restriction and exercise training. Studies have reported controversial findings about physical activity and its association with BDNF, but there is no comprehensive conclusions on this issue. The aim of this study was to systematically review the effects of exercise training on BDNF levels in patients with type 2 diabetes.

Methods

The electronic databases of Embase, Pedro, PubMed, Medline, Cochrane Library, as well as the Google Scholar search engine were used to obtain the related data about the role of exercise training on BDNF levels in patients with type 2 diabetes. The search period was set from inception to August 2019. Keywords of “exercise”, “training”, “physical activity”, “brain-derived neurotrophic factor”, “type 2 diabetes”, and “randomized clinical trials”, were used in persian and English. The PEDro scale was used to evaluate the quality of the included articles. Results. Finally, 11 articles (four human and seven animal articles) with medium to high quality were included in the study which 5 articles reported elevation (one human and four animal articles), 4 articles reported a reduction (one human and three animal articles), and 2 articles reported no changes (both of them in human articles) in BDNF level following the exercise training.

Conclusion

Decreased energy intake and increased energy expenditure through exercise training may modulate BDNF levels in patients with type 2 diabetes.

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Fig. 1

References

  1. 1.

    Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr. 2005;25:391–406. https://doi.org/10.1146/annurev.nutr.24.012003.132155.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–49. https://doi.org/10.1016/j.diabres.2013.11.002.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26:S5–20. https://doi.org/10.2337/diacare.26.2007.s5.

    Article  Google Scholar 

  4. 4.

    Duron E, Hanon O. Vascular risk factors, cognitive decline, and dementia. Vasc Health Risk Manag. 2008;4(2):363–81. https://doi.org/10.2147/vhrm.s1839.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100(10):1134–46. https://doi.org/10.1161/01.cir.100.10.1134.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Languren G, Montiel T, Julio-Amilpas A, Massieu L. Neuronal damage and cognitive impairment associated with hypoglycemia: an integrated view. Neurochem Int. 2013;63(4):331–43. https://doi.org/10.1016/j.neuint.2013.06.018.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Moreira RO, Soldera AL, Cury B, Meireles C, Kupfer R. Is cognitive impairment associated with the presence and severity of peripheral neuropathy in patients with type 2 diabetes mellitus? Diabetology & metabolic syndrome. 2015;7:51. https://doi.org/10.1186/s13098-015-0045-0.

    Article  Google Scholar 

  8. 8.

    Carsten RE, Whalen LR, Ishii DN. Impairment of spinal cord conduction velocity in diabetic rats. Diabetes. 1989;38(6):730–6. https://doi.org/10.2337/diab.38.6.730.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Yasuda H, Terada M, Maeda K, Kogawa S, Sanada M, Haneda M, et al. Diabetic neuropathy and nerve regeneration. Prog Neurobiol. 2003;69(4):229–85. https://doi.org/10.1016/s0301-0082(03)00034-0.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2015;11(6):718–26. https://doi.org/10.1016/j.jalz.2015.05.016.

    Article  Google Scholar 

  11. 11.

    Stewart R, Liolitsa D. Type 2 diabetes mellitus, cognitive impairment and dementia. Diabetic medicine : a journal of the British Diabetic Association. 1999;16(2):93–112. https://doi.org/10.1046/j.1464-5491.1999.00027.x.

    CAS  Article  Google Scholar 

  12. 12.

    Eslami R, Gharakhanlou R, Parnow A-H. The Response of Skeletal Muscle-Expressed Neurotrophins to Acute Resistance Exercise in Male Wistar Rats. Ann Appl Sport Sci. 2018;6(2):45–53. https://doi.org/10.29252/aassjournal.6.2.45.

    Article  Google Scholar 

  13. 13.

    Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736. https://doi.org/10.1146/annurev.neuro.24.1.677.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Rahmati-Ahmadabad S, Azarbayjani M, Nasehi M. The Effects of High-Intensity Interval Training with Supplementation of Flaxseed Oil on BDNF mRNA Expression and Pain Feeling in Male Rats. Ann Appl Sport Sci. 2017;5(4):1–12. https://doi.org/10.29252/aassjournal.5.4.1.

    Article  Google Scholar 

  15. 15.

    Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience. 2005;133(3):853–61. https://doi.org/10.1016/j.neuroscience.2005.03.026.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Phillips HS, Hains JM, Laramee GR, Rosenthal A, Winslow JW. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. Science. 1990;250(4978):290–4. https://doi.org/10.1126/science.1688328.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Fleischer A, Ghadiri A, Dessauge F, Duhamel M, Rebollo MP, Alvarez-Franco F, et al. Modulating apoptosis as a target for effective therapy. Mol Immunol. 2006;43(8):1065–79. https://doi.org/10.1016/j.molimm.2005.07.013.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Pedersen BK, Pedersen M, Krabbe KS, Bruunsgaard H, Matthews VB, Febbraio MA. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. Exp Physiol. 2009;94(12):1153–60. https://doi.org/10.1113/expphysiol.2009.048561.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Rashidlamir A, Hoseinzadeh M, Zeiaddini DL. The Effects of Resistance and Endurance Training on the Liver Tissue FNDC5 mRNA Gene Expression in Male Rats. Ann Appl Sport Sci. 2017;5(2):51–60. https://doi.org/10.18869/acadpub.aassjournal.5.2.51.

    Article  Google Scholar 

  20. 20.

    Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S. New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev. 2008;59(1):201–20. https://doi.org/10.1016/j.brainresrev.2008.07.007.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M. Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Brain Res Mol Brain Res. 1997;49(1–2):71–81. https://doi.org/10.1016/s0169-328x(97)00125-3.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Krabbe KS, Mortensen EL, Avlund K, Pedersen AN, Pedersen BK, Jorgensen T, et al. Brain-derived neurotrophic factor predicts mortality risk in older women. J Am Geriatr Soc. 2009;57(8):1447–52. https://doi.org/10.1111/j.1532-5415.2009.02345.x.

    Article  PubMed  Google Scholar 

  23. 23.

    Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007;101(1–3):239–44. https://doi.org/10.1016/j.jad.2006.11.005.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011;10(3):209–19. https://doi.org/10.1038/nrd3366.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Fujinami A, Ohta K, Obayashi H, Fukui M, Hasegawa G, Nakamura N, et al. Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem. 2008;41(10–11):812–7. https://doi.org/10.1016/j.clinbiochem.2008.03.003.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, et al. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007;50(2):431–8. https://doi.org/10.1007/s00125-006-0537-4.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Karczewska-Kupczewska M, Straczkowski M, Adamska A, Nikolajuk A, Otziomek E, Gorska M, et al. Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity. Clin Biochem. 2011;44(10–11):817–20. https://doi.org/10.1016/j.clinbiochem.2011.05.008.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Suwa M, Kishimoto H, Nofuji Y, Nakano H, Sasaki H, Radak Z, et al. Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabolism. 2006;55(7):852–7. https://doi.org/10.1016/j.metabol.2006.02.012.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403. https://doi.org/10.1056/NEJMoa012512.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Craft S. Insulin resistance and Alzheimer's disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res. 2007;4(2):147–52. https://doi.org/10.2174/156720507780362137.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Gasparini L, Xu H. Potential roles of insulin and IGF-1 in Alzheimer's disease. Trends Neurosci. 2003;26(8):404–6. https://doi.org/10.1016/s0166-2236(03)00163-2.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, et al. Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol. 2009;66(3):343–8. https://doi.org/10.1001/archneur.66.3.343.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hanninen T, et al. Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ (Clinical research ed). 1997;315(7115):1045–9. https://doi.org/10.1136/bmj.315.7115.1045.

    CAS  Article  Google Scholar 

  34. 34.

    Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat. 2006;20(4):216–23. https://doi.org/10.1016/j.jdiacomp.2005.07.005.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Cohen ND, Dunstan DW, Robinson C, Vulikh E, Zimmet PZ, Shaw JE. Improved endothelial function following a 14-month resistance exercise training program in adults with type 2 diabetes. Diabetes Res Clin Pract. 2008;79(3):405–11. https://doi.org/10.1016/j.diabres.2007.09.020.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Dinenno FA, Tanaka H, Monahan KD, Clevenger CM, Eskurza I, DeSouza CA, et al. Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men. J Physiol. 2001;534(Pt 1):287–95. https://doi.org/10.1111/j.1469-7793.2001.00287.x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017–22. https://doi.org/10.1073/pnas.1015950108.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Leckie RL, Oberlin LE, Voss MW, Prakash RS, Szabo-Reed A, Chaddock-Heyman L, et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci. 2014;8:985. https://doi.org/10.3389/fnhum.2014.00985.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kermani P, Rafii D, Jin DK, Whitlock P, Schaffer W, Chiang A, et al. Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors. J Clin Invest. 2005;115(3):653–63. https://doi.org/10.1172/jci22655.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell. 2007;130(4):691–703. https://doi.org/10.1016/j.cell.2007.06.054.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Mason JL, Xuan S, Dragatsis I, Efstratiadis A, Goldman JE. Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. J Neurosci. 2003;23(20):7710–8.

    CAS  Article  Google Scholar 

  42. 42.

    Messi ML, Delbono O. Target-derived trophic effect on skeletal muscle innervation in senescent mice. J Neurosci. 2003;23(4):1351–9.

    CAS  Article  Google Scholar 

  43. 43.

    Ola MS, Nawaz MI, El-Asrar AA, Abouammoh M, Alhomida AS. Reduced levels of brain derived neurotrophic factor (BDNF) in the serum of diabetic retinopathy patients and in the retina of diabetic rats. Cell Mol Neurobiol. 2013;33(3):359–67. https://doi.org/10.1007/s10571-012-9901-8.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Kishi T, Sunagawa K. Exercise training plus calorie restriction causes synergistic protection against cognitive decline via up-regulation of BDNF in hippocampus of stroke-prone hypertensive rats. Conference proceedings : Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual Conference. 2012;2012:6764–7. https://doi.org/10.1109/embc.2012.6347547.

    CAS  Article  Google Scholar 

  45. 45.

    Lee SS, Yoo JH, Kang S, Woo JH, Shin KO, Kim KB, et al. The effects of 12 weeks regular aerobic exercise on brain-derived Neurotrophic factor and inflammatory factors in juvenile obesity and type 2 diabetes mellitus. J Phys Ther Sci. 2014;26(8):1199–204. https://doi.org/10.1589/jpts.26.1199.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience. 2006;140(3):823–33. https://doi.org/10.1016/j.neuroscience.2006.02.084.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Mattson MP, Duan W, Wan R, Guo Z. Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx. 2004;1(1):111–6. https://doi.org/10.1602/neurorx.1.1.111.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Mattson MP, Maudsley S, Martin B. A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin. Ageing Res Rev. 2004;3(4):445–64. https://doi.org/10.1016/j.arr.2004.08.001.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996;726(1–2):49–56.

    CAS  Article  Google Scholar 

  50. 50.

    Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci. 2008;28(11):2278–87. https://doi.org/10.1111/j.1460-9568.2008.06524.x.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Vaynman S, Ying Z, Wu A, Gomez-Pinilla F. Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity. Neuroscience. 2006;139(4):1221–34. https://doi.org/10.1016/j.neuroscience.2006.01.062.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Johnson RA, Rhodes JS, Jeffrey SL, Garland T Jr, Mitchell GS. Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience. 2003;121(1):1–7. https://doi.org/10.1016/s0306-4522(03)00422-6.

    Article  PubMed  Google Scholar 

  53. 53.

    Rezaei M, Salarpor Kamarzard T, Najafian RM. The Effects of Neurofeedback, Yoga Interventions on Memory and Cognitive Activity in Children with Attention Deficit/Hyperactivity Disorder: A Randomized Controlled Trial. Ann Appl Sport Sci. 2018;6(4):17–27. https://doi.org/10.29252/aassjournal.6.4.17.

    Article  Google Scholar 

  54. 54.

    Castellano V, White LJ. Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis. J Neurol Sci. 2008;269(1–2):85–91. https://doi.org/10.1016/j.jns.2007.12.030.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Goekint M, Roelands B, De Pauw K, Knaepen K, Bos I, Meeusen R. Does a period of detraining cause a decrease in serum brain-derived neurotrophic factor? Neurosci Lett. 2010;486(3):146–9. https://doi.org/10.1016/j.neulet.2010.09.032.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Griffin EW, Mullally S, Foley C, Warmington SA, O'Mara SM, Kelly AM. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiol Behav. 2011;104(5):934–41. https://doi.org/10.1016/j.physbeh.2011.06.005.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Schiffer T, Schulte S, Hollmann W, Bloch W, Struder HK. Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2009;41(3):250–4. doi:https://doi.org/10.1055/s-0028-1093322.

  58. 58.

    Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2008;59(Suppl 7):119–32.

    Google Scholar 

  59. 59.

    Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83(8):713–21.

    Article  Google Scholar 

  60. 60.

    Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, et al. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. Journal of Alzheimer's disease : JAD. 2010;22(2):569–79. https://doi.org/10.3233/jad-2010-100768.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Stomby A, Otten J, Ryberg M, Nyberg L, Olsson T, Boraxbekk CJ. A Paleolithic diet with and without combined aerobic and resistance exercise increases functional brain responses and hippocampal volume in subjects with type 2 diabetes. Front Aging Neurosci. 2017;9:391. https://doi.org/10.3389/fnagi.2017.00391.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Swift DL, Johannsen NM, Myers VH, Earnest CP, Smits JA, Blair SN, et al. The effect of exercise training modality on serum brain derived neurotrophic factor levels in individuals with type 2 diabetes. PLoS One. 2012;7(8):e42785. https://doi.org/10.1371/journal.pone.0042785.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    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-e. https://doi.org/10.5812/ircmj.37757.

    Article  Google Scholar 

  64. 64.

    Hajizadeh Moghaddam A, Fallah Mohammadi Z, Sheikh P, Mirzaei S. The effect of voluntary jogging training on rotundum and allium paradoxoxium extracts on brain-derived neurotrophic factor levels in the hippocampus of alloxan-induced diabetic rats. Iranian Journal of Diabetes and Metabolism. 2012;11(4):350–7 [Article in persian].

    Google Scholar 

  65. 65.

    Kim H-J, So B, Son JS, Song HS, Oh SL, Seong JK, et al. Resistance training inhibits the elevation of skeletal muscle derived-BDNF level concomitant with improvement of muscle strength in zucker diabetic rat. J Exerc Nutrition Biochem. 2015;19(4):281–8. https://doi.org/10.5717/jenb.2015.15112402.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Rashidi Molaei R, Kazemi A, Rahmati M. The effect of a 6-week endurance training on BDNF and TrKB gene expression in the soleus of rats with diabetic neuropathy. J Kerman Univ Med Sci. 2016;23(6):741–53.

    Google Scholar 

  67. 67.

    Salehi I, Farajnia S, Mohammadi M, Sabouri Ghannad M. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats. Iranian Journal of Basic Medical Sciences. 2010;13(3):146–153. doi:https://doi.org/10.22038/ijbms.2010.5104.

  68. 68.

    Salehi OR, Hoseini A. The Effects of Endurance Trainings on Serum BDNF and Insulin Levels in Streptozotocin-Induced Diabetic Rats. The Neuroscience Journal of Shefaye-Khatam. 2017;5(2):52–61. https://doi.org/10.18869/acadpub.shefa.5.2.52.

    Article  Google Scholar 

  69. 69.

    Stranahan AM, Lee K, Martin B, Maudsley S, Golden E, Cutler RG, et al. Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus. 2009;19(10):951–61. https://doi.org/10.1002/hipo.20577.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Szuhany KL, Bugatti M, Otto MW. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatr Res. 2015;60:56–64. https://doi.org/10.1016/j.jpsychires.2014.10.003.

    Article  PubMed  Google Scholar 

  71. 71.

    Yarrow JF, White LJ, McCoy SC, Borst SE. Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF). Neurosci Lett. 2010;479(2):161–5. https://doi.org/10.1016/j.neulet.2010.05.058.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Karczewska-Kupczewska M, Kowalska I, Nikolajuk A, Adamska A, Zielinska M, Kaminska N, et al. Circulating brain-derived neurotrophic factor concentration is downregulated by intralipid/heparin infusion or high-fat meal in young healthy male subjects. Diabetes Care. 2012;35(2):358–62. https://doi.org/10.2337/dc11-1295.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33(12):e147–67. https://doi.org/10.2337/dc10-9990.

    Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, et al. Effects of exercise training on glucose homeostasis: the HERITAGE family study. Diabetes Care. 2005;28(1):108–14. https://doi.org/10.2337/diacare.28.1.108.

    Article  PubMed  Google Scholar 

  75. 75.

    King DS, Baldus PJ, Sharp RL, Kesl LD, Feltmeyer TL, Riddle MS. Time course for exercise-induced alterations in insulin action and glucose tolerance in middle-aged people. Journal of applied physiology (Bethesda, Md : 1985). 1995;78(1):17–22. doi:https://doi.org/10.1152/jappl.1995.78.1.17.

  76. 76.

    Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39(8):1423–34. https://doi.org/10.1249/mss.0b013e3180616b27.

    Article  PubMed  Google Scholar 

  77. 77.

    Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39(8):1435–45. https://doi.org/10.1249/mss.0b013e3180616aa2.

    Article  PubMed  Google Scholar 

  78. 78.

    Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee report, 2008. To the Secretary of Health and Human Services. Part A: executive summary. Nutrition reviews. 2009;67(2):114–20. doi:https://doi.org/10.1111/j.1753-4887.2008.00136.x.

  79. 79.

    Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews. 2015;4:1. https://doi.org/10.1186/2046-4053-4-1.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Shahnaz Shahrbanian or Seyed Morteza Tayebi.

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Jamali, A., Shahrbanian, S. & Morteza Tayebi, S. The Effects of Exercise Training on the Brain-Derived Neurotrophic Factor (BDNF) in the Patients with Type 2 Diabetes: A Systematic Review of the Randomized Controlled Trials. J Diabetes Metab Disord 19, 633–643 (2020). https://doi.org/10.1007/s40200-020-00529-w

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Keywords

  • Exercise
  • Training
  • Brain-derived Neurotrophic factor
  • Type 2 diabetes
  • Systematic review