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Sports Medicine

, Volume 43, Issue 11, pp 1191–1199 | Cite as

Effects of Exercise Training on Arterial Function in Type 2 Diabetes Mellitus

A Systematic Review and Meta-Analysis
  • David MonteroEmail author
  • Guillaume Walther
  • Eric Benamo
  • Antonia Perez-Martin
  • Agnès Vinet
Systematic Review

Abstract

Background and Objective

Controversy exists among trials assessing whether exercise can improve arterial function in type 2 diabetes mellitus (T2DM) subjects. Therefore the aim of this study was to systematically review and quantify the effects of exercise on arterial function in T2DM subjects.

Methods

MEDLINE, Cochrane, Scopus and Web of Science were searched up until January 2013 for randomized controlled trials evaluating the effects of exercise interventions lasting 4 weeks or more on arterial function in T2DM subjects. Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial conduit artery were considered for assessment of arterial endothelial function and smooth muscle function, respectively.

Results

Five randomized trials comparing exercise and control groups (overall n = 217) met the inclusion criteria. The mean exercise characteristics were as follows: 3.6 sessions per week, 67.5 min per session, intensity at 74.4 % of the maximum heart rate (HRmax), for 14 weeks. The post-intervention mean difference in FMD favoured the exercise groups over the control groups (2.23 %; P < 0.0001). No significant post-intervention mean difference in NMD (1.22 %; P = 0.29) was found between the groups. Neither heterogeneity nor publication bias was detected among the trials.

Conclusion

Exercise training alone improved FMD, showing its capacity to restore arterial endothelial function in T2DM subjects. However, further research is needed to determine whether longer and/or more intense exercise interventions could enhance arterial smooth muscle function in this population.

Keywords

Exercise Training Arterial Function Exercise Training Intervention Smooth Muscle Dysfunction Cuff Placement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The study was supported by grants from the French Society of Vascular Medicine in 2010–2012 (to A.V. and A.P.M.).

The authors have no conflicts of interest that are directly relevant to the content of this article.

Supplementary material

40279_2013_85_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 32 kb)

References

  1. 1.
    Sigal RJ, Kenny GP, Wasserman DH, et al. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(6):1433–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Boule NG, Haddad E, Kenny GP, et al. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001;286(10):1218–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Balducci S, Leonetti F, Di Mario U, et al. Is a long-term aerobic plus resistance training program feasible for and effective on metabolic profiles in type 2 diabetic patients? Diabetes Care. 2004;27(3):841–2.PubMedCrossRefGoogle Scholar
  4. 4.
    Boule NG, Kenny GP, Haddad E, et al. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46(8):1071–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Hakim AA, Petrovitch H, Burchfiel CM, et al. Effects of walking on mortality among nonsmoking retired men. N Engl J Med. 1998;338(2):94–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Hu FB, Stampfer MJ, Solomon C, et al. Physical activity and risk for cardiovascular events in diabetic women. Ann Intern Med. 2001;134(2):96–105.PubMedCrossRefGoogle Scholar
  7. 7.
    Wei M, Gibbons LW, Kampert JB, et al. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med. 2000;132(8):605–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Mora S, Cook N, Buring JE, et al. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation. 2007;116(19):2110–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Joyner MJ, Green DJ. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol. 2009;587(Pt 23):5551–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Ignarro LJ. Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol. 2002;53(4 Pt 1):503–14.PubMedGoogle Scholar
  11. 11.
    Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115(10):1285–95.PubMedGoogle Scholar
  12. 12.
    Corretti MC, Anderson TJ, Benjamin EJ, 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Harris RA, Nishiyama SK, Wray DW, et al. Ultrasound assessment of flow-mediated dilation. Hypertension. 2010;55(5):1075–85.PubMedCrossRefGoogle Scholar
  15. 15.
    Thijssen DH, Black MA, Pyke KE, 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Shechter M, Issachar A, Marai I, et al. Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol. 2009;134(1):52–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Yeboah J, Folsom AR, Burke GL, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120(6):502–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Kullo IJ, Malik AR, Bielak LF, et al. Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults. Clin Sci (Lond). 2007;112(3):175–82.CrossRefGoogle Scholar
  19. 19.
    Akamatsu D, Sato A, Goto H, et al. Nitroglycerin-mediated vasodilatation of the brachial artery may predict long-term cardiovascular events irrespective of the presence of atherosclerotic disease. J Atheroscler Thromb. 2010;17(12):1266–74.PubMedCrossRefGoogle Scholar
  20. 20.
    Kawano N, Emoto M, Mori K, et al. Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients. J Atheroscler Thromb. 2012;19(3):276–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Bruno RM, Penno G, Daniele G, et al. Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia. 2012;55(6):1847–55.PubMedCrossRefGoogle Scholar
  22. 22.
    Tan KC, Chow WS, Ai VH, et al. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care. 2002;25(6):1055–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Hamdy O, Ledbury S, Mullooly C, et al. Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome. Diabetes Care. 2003;26(7):2119–25.PubMedCrossRefGoogle Scholar
  24. 24.
    Barone Gibbs B, Dobrosielski DA, Bonekamp S, Stewart KJ, Clark JM. 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. doi: 10.1016/j.atherosclerosis.2012.07.035.Google Scholar
  25. 25.
    Kwon HR, Min KW, Ahn HJ, et al. 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Maiorana A, O’Driscoll G, Cheetham C, 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Okada S, Hiuge A, Makino H, 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Ainsworth BE, Haskell WL, Herrmann SD, et al. 2011 compendium of physical activities: a second update of codes and MET values. Med Sci Sports Exerc. 2011;43(8):1575–81.PubMedCrossRefGoogle Scholar
  30. 30.
    Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334–59.PubMedCrossRefGoogle Scholar
  31. 31.
    Bhogal SK, Teasell RW, Foley NC, et al. The PEDro scale provides a more comprehensive measure of methodological quality than the Jadad scale in stroke rehabilitation literature. J Clin Epidemiol. 2005;58(7):668–73.PubMedCrossRefGoogle Scholar
  32. 32.
    de Morton NA. The PEDro scale is a valid measure of the methodological quality of clinical trials: a demographic study. Aust J Physiother. 2009;55(2):129–33.PubMedCrossRefGoogle Scholar
  33. 33.
    Maher CG, Sherrington C, Herbert RD, et al. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83(8):713–21.PubMedGoogle Scholar
  34. 34.
    Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions: version 5.1.0 [updated March 2011]. The Cochrane Collaboration (2011). http://www.cochrane-handbook.org. Accessed 24 Jul 2013.
  35. 35.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.PubMedCrossRefGoogle Scholar
  36. 36.
    Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Sixt S, Beer S, Bluher M, et al. Long- but not short-term multifactorial intervention with focus on exercise training improves coronary endothelial dysfunction in diabetes mellitus type 2 and coronary artery disease. Eur Heart J. 2010;31(1):112–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Wycherley TP, Brinkworth GD, Noakes M, 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.PubMedCrossRefGoogle Scholar
  39. 39.
    Green DJ, Maiorana AJ, Tschakovsky ME, et al. Relationship between changes in brachial artery flow-mediated dilation and basal release of nitric oxide in subjects with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2006;291(3):H1193–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Green DJ, Walsh JH, Maiorana A, 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.PubMedGoogle Scholar
  41. 41.
    Middlebrooke AR, Elston LM, Macleod KM, et al. Six months of aerobic exercise does not improve microvascular function in type 2 diabetes mellitus. Diabetologia. 2006;49(10):2263–71.PubMedCrossRefGoogle Scholar
  42. 42.
    Choi KM, Han KA, Ahn HJ, 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Enderle MD, Benda N, Schmuelling RM, et al. Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects. Diabetes Care. 1998;21(2):271–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Ifrim S, Vasilescu R. Early detection of atherosclerosis in type 2 diabetic patients by endothelial dysfunction and intima-media thickness. Rom J Intern Med. 2004;42(2):343–54.PubMedGoogle Scholar
  45. 45.
    Ihlemann N, Stokholm KH, Eskildsen PC. Impaired vascular reactivity is present despite normal levels of von Willebrand factor in patients with uncomplicated type 2 diabetes. Diabet Med. 2002;19(6):476–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Woodman RJ, Watts GF, Puddey IB, et al. Leukocyte count and vascular function in type 2 diabetic subjects with treated hypertension. Atherosclerosis. 2002;163(1):175–81.PubMedCrossRefGoogle Scholar
  47. 47.
    Brooks BA, Franjic B, Ban CR, et al. Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes. Diabetes Obes Metab. 2008;10(9):739–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Vehkavaara S, Yki-Jarvinen H. 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2004;24(2):325–30.PubMedCrossRefGoogle Scholar
  49. 49.
    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.PubMedCrossRefGoogle Scholar
  50. 50.
    Tinken TM, Thijssen DH, Black MA, et al. Time course of change in vasodilator function and capacity in response to exercise training in humans. J Physiol. 2008;586(Pt 20):5003–12.PubMedCrossRefGoogle Scholar
  51. 51.
    Tinken TM, Thijssen DH, Hopkins N, et al. Shear stress mediates endothelial adaptations to exercise training in humans. Hypertension. 2010;55(2):312–8.PubMedCrossRefGoogle Scholar
  52. 52.
    da Silva CA, Ribeiro JP, Canto JC, 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.PubMedCrossRefGoogle Scholar
  53. 53.
    Miche E, Herrmann G, Nowak M, et al. Effect of an exercise training program on endothelial dysfunction in diabetic and non-diabetic patients with severe chronic heart failure. Clin Res Cardiol. 2006;95(Suppl 1):i117–24.PubMedCrossRefGoogle Scholar
  54. 54.
    Thijssen DH, Dawson EA, Black MA, et al. Brachial artery blood flow responses to different modalities of lower limb exercise. Med Sci Sports Exerc. 2009;41(5):1072–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Green DJ, Bilsborough W, Naylor LH, et al. Comparison of forearm blood flow responses to incremental handgrip and cycle ergometer exercise: relative contribution of nitric oxide. J Physiol. 2005;562(Pt 2):617–28.PubMedCrossRefGoogle Scholar
  56. 56.
    Ayer JG, Harmer JA, David C, et al. Severe obesity is associated with impaired arterial smooth muscle function in young adults. Obesity (Silver Spring). 2011;19(1):54–60.CrossRefGoogle Scholar
  57. 57.
    Leeson P, Thorne S, Donald A, et al. Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart. 1997;78(1):22–7.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • David Montero
    • 1
    • 3
    Email author
  • Guillaume Walther
    • 1
  • Eric Benamo
    • 1
  • Antonia Perez-Martin
    • 2
  • Agnès Vinet
    • 1
  1. 1.Avignon UniversityAvignonFrance
  2. 2.Vascular Medicine UnitNimes University HospitalNimesFrance
  3. 3.Applied Biology Department, Nutrition/Institute of BioengineeringMiguel Hernandez UniversityElcheSpain

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