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03-06-2018 | Physical activity | Review | Article

The effects of exercise on vascular endothelial function in type 2 diabetes: a systematic review and meta-analysis

Journal: Diabetology & Metabolic Syndrome

Authors: Jung-Hoon Lee, Ruda Lee, Moon-Hyon Hwang, Marc T. Hamilton, Yoonjung Park

Publisher: BioMed Central




Vascular endothelial dysfunction induced by hyperglycemia and elevated insulin resistance is a potent risk factor for cardiovascular disease and likely contributes to multiple chronic disease complications associated with aging. The aim of this study was to systematically review and quantify the effects of exercise on endothelial function (EF) in type 2 diabetes (T2D).


Five electronic databases were searched (until June 2017) for studies that met the following criteria: (i) randomized controlled trials; (ii) T2D aged ≥ 18 years; (iii) measured EF by brachial artery flow-mediated dilation (FMD); (iv) structured and supervised exercise intervention for ≥ 8 weeks.


Thirteen cohorts, selected from eight studies (306 patients, average age 59 years), met the inclusion criteria. Exercise training significantly increased FMD (mean ES = 0.41, 95% CI 0.21–0.62, P < 0.001). Low to moderate intensity subgroups and aerobic exercise (AE) subgroups significantly increased FMD more than moderate to high intensity subgroups and combined AE and resistance exercise subgroups respectively (P < 0.01, P < 0.05). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments reported that quality of evidence for all outcomes was moderate except shear rate showing low. Egger’s test showed no significant publication bias for all outcomes.


Our results suggest that in patients with T2D, lower intensity exercise has physiological meaningful effects on EF, in support of the emerging concept that the lower efforts of exercise are not necessarily less cardioprotective than higher intensity training.
Fox CS, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the framingham heart study. Circulation. 2007;115(12):1544–50. CrossRefPubMed
Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007;3(6):853–76. PubMedPubMedCentral
Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am. 2008;37(3):685–711. CrossRefPubMedPubMedCentral
Thijssen DH, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol-Heart Circ Physiol. 2011;300(1):H2–12. CrossRefPubMed
Vita JA, Keaney JF. Endothelial function. Am Heart Assoc. 2002;106:640–2.
Corretti MC, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39(2):257–65. CrossRefPubMed
Vane JR, Änggård EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323(1):27–36. CrossRefPubMed
Ando J, Yamamoto K. Effects of shear stress and stretch on endothelial function. Antioxid Redox Signal. 2011;15(5):1389–403. CrossRefPubMed
Larisa Way K, et al. The effect of exercise on vascular function and stiffness in type 2 diabetes: a systematic review and meta-analysis. Curr Diabetes Rev. 2016;12(4):369–83. CrossRef
Montero D, et al. Effects of exercise training on arterial function in type 2 diabetes mellitus. Sports Med. 2013;43(11):1191–9. CrossRefPubMed
Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction. Circulation. 2007;115(10):1285–95. PubMed
Liberati A, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. CrossRefPubMedPubMedCentral
Guyatt GH, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clin Res ed.). 2008;336(7650):924–6. CrossRef
Andrews J, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol. 2013;66(7):719–25. CrossRefPubMed
Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010;26(6):631–40. CrossRefPubMed
Cochran WG. Some methods for strengthening the common χ 2 tests. Biometrics. 1954;10(4):417–51. CrossRef
Higgin J, et al. Measuring inconsistency in meta-analysis. BMJ. 2003;327:557–60. CrossRef
Cohen J. Statistical power analysis for the behavioral sciences Lawrence Earlbaum Associates. Hillsdale: NJ; 1988. p. 20–6.
Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. http://​www.​cochranehandbook​.​org.
Egger M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. CrossRefPubMedPubMedCentral
Green DJ, et al. Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations. Am J Physiol-Heart Circ Physiol. 2003;285(6):H2679–87. CrossRefPubMed
Green DJ, et al. Comparison of resistance and conduit vessel nitric oxide-mediated vascular function in vivo: effects of exercise training. J Appl Physiol. 2004;97(2):749–55. CrossRefPubMed
Madsen SM, et al. Functional and structural vascular adaptations following 8 weeks of low volume high intensity interval training in lower leg of type 2 diabetes patients and individuals at high risk of metabolic syndrome. Arch Physiol Biochem. 2015;121(5):178–86. CrossRefPubMed
da Silva CA, et al. High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus. Diabetes Res Clin Pract. 2012;95(2):237–45. CrossRefPubMed
Silva CAD, et al. Effect of high-intensity exercise on endothelial function in patients with T2DM. Revista Brasileira de Medicina do Esporte. 2016;22(2):126–30. CrossRef
Allen JD, et al. Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training. J Diabetes Complicat. 2014;28(2):219–25. CrossRefPubMed
Kluding PM, et al. Safety of aerobic exercise in people with diabetic peripheral neuropathy: single-group clinical trial. Phys Ther. 2015;95(2):223. CrossRefPubMed
Billinger SA, et al. Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy. Int J Neurosci. 2017;127(1):80–5. CrossRefPubMed
Maiorana A, et al. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol. 2001;38(3):860–6. CrossRefPubMed
Choi KM, et al. Effects of exercise on sRAGE levels and cardiometabolic risk factors in patients with type 2 diabetes: a randomized controlled trial. J Clin Endocrinol Metab. 2012;97(10):3751–8. CrossRefPubMed
Wycherley TP, et al. Effect of caloric restriction with and without exercise training on oxidative stress and endothelial function in obese subjects with type 2 diabetes. Diabetes Obes Metab. 2008;10(11):1062–73. CrossRefPubMed
Wycherley TP, et al. Long-term effects of weight loss with a very-low carbohydrate, low saturated fat diet on flow mediated dilatation in patients with type 2 diabetes: a randomised controlled trial. Atherosclerosis. 2016;252:28–31. CrossRefPubMed
Schreuder TH, et al. Life-long physical activity restores metabolic and cardiovascular function in type 2 diabetes. Eur J Appl Physiol. 2014;114(3):619–27. CrossRefPubMed
Xinghai L. Effect of Qigong Baduanjin on endothelium-dependent arterial dilation of type 2 diabetes. J Shenyang Sport Univ. 2009;1:013.
Rittig K, et al. Reducing visceral adipose tissue mass is essential for improving endothelial function in type 2 diabetes prone individuals. Atherosclerosis. 2010;212(2):575–9. CrossRefPubMed
Han KA, et al. Effects of moderate versus vigorous intensity exercise training on inflammatory markers, endothelial function, and insulin resistance in the patients with type 2 diabetes: longitudinal study in diabetes. Alexandria: Amer Diabetes Assoc; 2009.
Dhungana R, et al. Exercise effects on a novel marker of local shear stress and brachial artery flow-mediated dilation. J Am Coll Cardiol. 2012;59(13):E1746. CrossRef
Suntraluck S, Tanaka H, Suksom D. The relative efficacy of land-based and water-based exercise training on macro-and micro-vascular functions in older patients with type 2 diabetes. J Aging Phys Act. 2017;25(3):446–52. CrossRefPubMed
Francois ME, Durrer C, Little J. High-intensity interval training with or without post-exercise milk consumption improves cardiovascular function in patients with type 2 diabetes. FASEB J. 2017;31(1 Supplement):1035.2.
Schreuder TH, et al. Impact of hypoxic versus normoxic training on physical fitness and vasculature in diabetes. High Alt Med Biol. 2014;15(3):349–55. CrossRefPubMed
Schreuder TH, et al. Randomized controlled trial using bosentan to enhance the impact of exercise training in subjects with type 2 diabetes mellitus. Exp Physiol. 2014;99(11):1538–47. CrossRefPubMed
Gainey A, et al. Effects of Buddhist walking meditation on glycemic control and vascular function in patients with type 2 diabetes. Complement Ther Med. 2016;26:92–7. CrossRefPubMed
Kwon HR. Effects of aerobic exercise vs resistance training on endothelial function in women with type 2 diabetes mellitus. Diabetes Metab J. 2011;35(4):364–73. CrossRefPubMedPubMedCentral
Okada S, et al. Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes. J Atheroscler Thromb. 2010;17(8):828–33. CrossRefPubMed
Schreuder TH, et al. Time-course of vascular adaptations during 8 weeks of exercise training in subjects with type 2 diabetes and middle-aged controls. Eur J Appl Physiol. 2015;115(1):187–96. CrossRefPubMed
Barone Gibbs B, et al. A randomized trial of exercise for blood pressure reduction in type 2 diabetes: effect on flow-mediated dilation and circulating biomarkers of endothelial function. Atherosclerosis. 2012;224(2):446–53. CrossRefPubMedPubMedCentral
Mitranun W, et al. Continuous vs interval training on glycemic control and macro- and microvascular reactivity in type 2 diabetic patients. Scand J Med Sci Sports. 2014;24(2):e69–76. CrossRefPubMed
Ignarro L. Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol. 2002;53(4):503–14. PubMed
Tousoulis D, et al. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2012;10(1):4–18. CrossRefPubMed
Di Francescomarino S, et al. The effect of physical exercise on endothelial function. Sports Med. 2009;39(10):797. CrossRefPubMed
Higashi Y, Yoshizumi M. Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther. 2004;102(1):87–96. CrossRefPubMed
Hwang M-H, Kim S. Type 2 diabetes: endothelial dysfunction and exercise. J Exerc Nutr Biochem. 2014;18(3):239. CrossRef
Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci. 2005;109(2):143–59. CrossRefPubMed
Thijssen DH, et al. Impact of inactivity and exercise on the vasculature in humans. Eur J Appl Physiol. 2010;108(5):845–75. CrossRefPubMed
Green DJ, et al. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol. 2004;561(1):1–25. CrossRefPubMedPubMedCentral
Tinken TM, et al. Shear stress mediates endothelial adaptations to exercise training in humans. Hypertension. 2010;55(2):312–8. CrossRefPubMed
Thijssen D, et al. Exercise training modulates the pattern of diameter change of the flow-mediated dilation in healthy young men. Acta Physiol. 2011;201:427–34. CrossRef
Newcomer SC, Thijssen DH, Green DJ. Effects of exercise on endothelium and endothelium/smooth muscle cross talk: role of exercise-induced hemodynamics. J Appl Physiol. 2011;111(1):311–20. CrossRefPubMed
Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J Physiol. 2005;568(2):357–69. CrossRefPubMedPubMedCentral
Alzheimer’s A. Alzheimer’s disease facts and figures. Alzheimer’s Dementia. 2013;9(2):1–71. CrossRef
Yoshizawa M, et al. Effect of 12 weeks of moderate—intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32–59 years. Br J Sports Med. 2009;43(8):615–8. CrossRefPubMed
Miyachi M. Effects of resistance training on arterial stiffness: a meta-analysis. Br J Sports Med. 2013;47(6):393–6. CrossRefPubMed
Joris PJ, Zeegers MP, Mensink RP. Weight loss improves fasting flow-mediated vasodilation in adults: a meta-analysis of intervention studies. Atherosclerosis. 2015;239(1):21–30. CrossRefPubMed
Sampaio RAC, et al. Arterial stiffness is associated with low skeletal muscle mass in Japanese community-dwelling older adults. Geriatr Gerontol Int. 2014;14(S1):109–14. CrossRefPubMed
Kim TN, et al. Skeletal muscle mass to visceral fat area ratio is associated with metabolic syndrome and arterial stiffness: the Korean sarcopenic obesity study (KSOS). Diabetes Res Clin Pract. 2011;93(2):285–91. CrossRefPubMed
Ohara M, et al. Sarcopenic obesity and arterial stiffness, pressure wave reflection and central pulse pressure: the J-SHIPP study. Int J Cardiol. 2014;174(1):214–7. CrossRefPubMed
Miller W, Sherman W, Ivy J. Effect of strength training on glucose tolerance and post-glucose insulin response. Med Sci Sports Exerc. 1984;16(6):539–43. CrossRefPubMed
American Diabetes Association. Statistics about diabetes. 2017. http://​www.​diabetes.​org/​diabetes-basics/​statistics/​. Accessed 5 Apr 2017.
Lindle RS, et al. Age and gender comparisons of muscle strength in 654 women and men aged 20–93 year. J Appl Physiol. 1997;83(5):1581–7. CrossRefPubMed
Baumgartner RN, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147(8):755–63. CrossRefPubMed

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