The Effect of 3 Months of Aerobic Training on TNF-α and Insulin Resistance in Obese Men with Type 2 Diabetes

Document Type : Research Paper


1 Assistant Professor of Exercise Physiology, Faculty of Humanities, Islamic Azad University, Saveh Branch, Saveh, Iran

2 Associate Professor of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Islamic Azad University, Islamshahr Branch, Islamshahr, Iran


This study aimed at determining the effect of aerobic training on Tumor necrosis factor-alpha (TNF-α) and insulin resistance in males with type 2 diabetes. 30 inactive adult obese men (30≤BMI≤36) with type 2 diabetes were randomly divided into experimental (n=15) and control (n=15) groups. The experimental subjects participated in three months of aerobic training (3 sessions per week) at %60–75 HRmax. Serum levels of TNF-α, glucose and insulin resistance were measured before and 48 hours after the last training session. Independent t test was used to compare variables at baseline. Paired t test was used to determine the effect of training program on variables. Kolmogorov-Smirnov was applied to determine the normal distribution of data. Aerobic intervention significantly decreased glucose (P=0.001) and insulin resistance (P=0.034) and did not change TNF-α (P=0.83). Despite the lack of change in TNF-α, 3 months of aerobic training was accompanied with a significant improvement in glucose and insulin resistance in type 2 diabetes patients. Based on our findings and other available evidence, improvement in glycemic profile and insulin resistance can be attributed to the changes in other hormonal or metabolic mediators that needs more studies in this area.


1.   Klöting N FM, Dietrich A, Kovacs P, Schön MR, Kern M. Insulin sensitive obesity. American Journal of  Physiology Endocrinol Metabolic. 2010. [Epub ahead of print].
2.   Gustafson B. Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb. 2010;17(4):332-41.
3.   Samaras K BN, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity 2010;18(5):884-9.
4.   Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab. 2009;94(9):3171-82.
5.   Stefanyk LE, Dyck DJ. The interaction between adipokines, diet and exercise on muscle insulin sensitivity. Curr Opin Clin Nutr Metab Care. 2010;13(3):255-9.
6.   Abd El-Kader S, Gari A, Salah El-Den A. Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial. Afr Health Sci. 2013;13(4):857-63.
7.   Jovinge S, Hamsten A, Tornvall P, Proudler A, Båvenholm P, Ericsson CG, et al. Evidence for a role of tumor necrosis factor alpha in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease. Metabolism. 1998;47(1):113-8.
8.   Nilsson-Ohman J, Fredrikson GN, Nilsson-Berglund LM, Gustavsson C, Bengtsson E, Smith ML, et al. Tumor necrosis factor-alpha does not mediate diabetes-induced vascular inflammation in mice. Arterioscler Thromb Vasc Biol. 2009;29(10):1465-70.
9.   Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res. 2002;10(11):1104-10.
10. Phillips MD, Patrizi RM, Cheek DJ, Wooten JS, Barbee JJ, Mitchell JB. Resistance training reduces subclinical inflammation in obese, postmenopausal women. Med Sci Sports Exerc. 2012;44(11):2099-110.
11. You T AN, 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.
12. Pedersen BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem. 2006;42:105-17.
13. Wenning P, Kreutz T, Schmidt A, Opitz D, Graf C, Voss S, et al. Endurance exercise alters cellular immune status and resistin concentrations in men suffering from non-insulin-dependent type 2 diabetes. Exp Clin Endocrinol Diabetes. 2013;121(8):475-82.
14. Lebon J, Riesco E, Tessier D, Dionne IJ. Additive effects of isoflavones and exercise training on inflammatory cytokines and body composition in overweight and obese postmenopausal women: a randomized controlled trial. Menopause. 2014;21(8):869-75.
15. Oh EG, Bang SY, Kim SH, Hyun SS, Chu SH, Jeon JY, et al. Therapeutic lifestyle modification program reduces plasma levels of the chemokines CRP and MCP-1 in subjects with metabolic syndrome. Biol Res Nurs. 2013;15(1):48-55.
16. Arslan M, Ipekci SH, Kebapcilar L, Dogan Dede N, Kurban S, Erbay E, Gonen MS. Effect of Aerobic Exercise Training on MDA and TNF- α Levels in Patients with Type 2 Diabetes Mellitus. Int Sch Res Notices. 2014:820387.
17. Many G, Hurtado ME, Tanner C, Houmard J, Gordish-Dressman H, Park JJ, et al. Pediatr Exerc Sci. Moderate-intensity aerobic training program improves insulin sensitivity and inflammatory markers in a pilot study of morbidly obese minority teens. Pediatr Exerc Sci. 2013;25(1):12-26.
18. Michael IP, John D, Smith G, Richard G. Accuracy of the Omron HBF-500 Body Composition Monitor in Male and Female College Students. Int J Exerc Sci. 2011;4(1):93-101.
19. Afreen AC, Krishnananda P. An Association of High Sensitive C Reactive Protein and Lipid Profile Parameters in South Indian Population. International Journal of Scientific and Research Publications. 2013;3(7):1-3.
20. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical activity/ exercise and type 2 diabetes. Diabetes Care. 2004;27(10):2518-39.
21. Abd El-Kader SM, Al-Jiffri OH, Al-Shreef FM. Aerobic exercises alleviate symptoms of fatigue related to inflammatory cytokines in obese patients with type 2 diabetes. Afr Health Sci. 2015;15(4):1142-8.
22. Pederson BK. Exercise and cytokines. Immonology and Cell Biology. 2000;5: 532-5.
23. Kadoglou NP, Iliadis F, Angelopoulou N, Perrea D, Ampatzidis G, Liapis CD, Alevizos M. The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. Eur J Cardiovasc Prev Rehabil. 2007;14(6):837-43.
24. Zoppini G, Targher G, Zamboni C, Venturi C, Cacciatori V, Moghetti P, Muggeo M. Effects of moderate-intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes. Nutr Metab Cardiovasc Dis. 2006;16(8):543-9.
25. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316(2):129-39.
26. Merghani TH, Alawad AO, Ballal MA. Plasma TNF-α in obese patient with diabetes and its relation to resting metabolic rate. Journal of Diabetology. 2014;5(1):1-6.
27. Yamagishi S, Adachi H, Matsui T, Nakamura K, Enomoto M, Fukami A, et al. Decreased high-density lipoprotein cholesterol level is an independent correlate of circulating tumor necrosis factor-alpha in a general population. Clin Cardiol. 2009;32(9):29-32.
28. Liang H, Yin B, Zhang H, Zhang S, Zeng Q, Wang J, et al. Blockade of Tumor necrosis factor (TNF) receptor type 1-mediated TNF-α signaling protected wistar rats from diet-induced obesity and insulin resistance. Endocrinology. 2008;149(6):2943-51.
29. Skolnik EY, Marcusohn J. Inhibition of insulin receptor signaling by TNF: potential role in obesity and non-insulin-dependent diabetes mellitus. Cytokine Growth Factor Rev. 1996;7(2):161-73.
30. Moller DE. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabete. Trends Endocrinol Metab. 2000;11(6):212-7.
31. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest. 1995;95(5):2409-15.
32. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87-91.
33. Hofmann C, Lorenz K, Braithwaite SS, Colca JR, Palazuk BJ, Hotamisligil GS, Spiegelman BM.  Altered gene expression for tumor necrosis factor-α and its receptors during drug and dietary modulation of insulin resistance. Endocrinology. 1994;134(1):264-70.
34. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-α in serum of obese patients: fall with weight loss. J Clin Endocrinol Metab. 1998;83(8):2907-10.
35. Abd El-Kader MS, Al-Jiffri O, Ashmawy EM. Impact of weight loss on markers of systemic inflammation in obese Saudi children with asthma. Afr Health Sci. 2013;13(3):682-8.
36. Zwetsloot KA, John CS, Lawrence MM, Battista RA, Shanely RA. High-intensity interval training induces a modest systemic inflammatory response in active, young men. J Inflamm Res. 2014;9(7):9-17.
37. AAuerbach P, Nordby P, Bendtsen LQ, Mehlsen JL, Basnet SK, Vestergaard H, et al. Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am J Physiol Regul Integr Comp Physiol. 2013;305(5):490-8.
38. Bouchonville M, Armamento-Villareal R, Shah K, Napoli N, Sinacore DR, Qualls C, Villareal DT. Weight loss, exercise or both and cardiometabolic risk factors in obese older adults: results of a randomized controlled trial. Int J Obes 2014;38(3):423-31.
39. Riesco E, Tessier S, Lacaille M, Pérusse F, Côté M, Després JP, et al. Impact of a moderate-intensity walking program on cardiometabolic risk markers in overweight to obese women: is there any influence of menopause? . Menopause. 2013;20(2):185-93.
40. Eisanezhad A, Hassan Saraf Z, Mahdavi M, Ghakhanlu R. The Effect of Aerobic Exercise Training on Serum Levels of TNF-α, IL - 1β, IL-6 and Hsp70 in Rats. Journal of Sport Biosciences. 2013;4(15):91-106.
41. Cavagnolli DA, Esteves AM, Ackel-D'Elia C, Maeda MY, de Faria AP, Tufik S, de Mello MT.  Aerobic exercise does not change C-reactive protein levels in non-obese patients with obstructive sleep apnoea. Eur J Sport Sci. 2014;14(1):142-7.
42. Wei SS, Liang DD. The effect of exercises on TNF-alpha, IL-6 and adiponectin in different fat diet rats. 2013;29(3):280-2.
43. Johnson WD, Brashear MM, Gupta AK, Rood JC, Ryan DH. Incremental weight loss improves cardiometabolic risk in extremely obese adults. Am J Med. 2011;1124(10):931-8.
44. Donges CE, Duffield R, Guelfi KJ, Smith GC, Adams DR, Edge JA. Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men. Appl Physiol Nutr Metab. 2013;38(7):779-88.
45. Czajkowska JB, Shutty B, Zito S. Development of Low Blood Glucose Readings in Nine Non-patients with diabetes Treated With Tumor Necrosis Factor-alpha Inhibitors. J Med Case Rep. 2012;6:5.
46. Lechleitner M, Herold M, Dzien-Bischinger C, Hoppichler F, Dzien A. Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years. Diabet Med. 2002;19(11):949-53.
47. Gielen S, Adams V, Möbius-Winkler S, Linke A, Erbs S, Yu J, et al. Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol. 2003;42(5):861-8.
48. Pashaei S, Bakhtiyari S, Haghani K, Maleki F A. Investigating the Effects of TNF-α knockdown Gene on Insulin Resistance in C2C12 Muscle Cells in the Presence and Absence of Palmitate. Iranian Journal of Endocrinology and Metabolism. 2013;15(4):387-94.
49. Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z. Review on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br J Sports Med. 2010;44(9):620-30.
50. Kraemer RR, Aboudehen KS, Carruth AK, Durand RT, Acevedo EO, Hebert EP, et al. Adiponectin responses to continuous and progressively intense intermittent exercise. Med Sci Sports Exerc. 2003;35(8):1320-5.