Effects of metformin and exercise training, alone or in association, on cardio-pulmonary performance and quality of life in insulin resistance patients

Cardiovascular Diabetology

Giuseppe Mercuro¹  Marco Giorgio Baroni¹  Efisio Cossu¹  Stefano Bandinu¹  Orru Fabio¹  Alessandro Bina¹  Martino Deidda¹  Cugusi Lucia¹  Silvio Nocco¹  Christian Cadeddu¹ 

[1] Department of Medical Sciences “M. Aresu”, University Hospital of Cagliari, SS 554, Km 4.500, 09042 Monserrato, Italy

关键词: Quality of life;    Exercise training;    Metformin;    Cardiopulmonary exercise test;    Insulin resistance;   

Others  :  792954
DOI  :  10.1186/1475-2840-13-93

 received in 2014-01-02, accepted in 2014-05-03,  发布年份 2014

【 摘 要 】

Background

Metformin (MET) therapy exerts positive effects improving glucose tolerance and preventing the evolution toward diabetes in insulin resistant patients. It has been shown that adding MET to exercise training does not improve insulin sensitivity. The aim of this study was to determine the effect of MET and exercise training alone or in combination on maximal aerobic capacity and, as a secondary end-point on quality of life indexes in individuals with insulin resistance.

Methods

75 insulin resistant patients were enrolled and subsequently assigned to MET (M), MET with exercise training (MEx), and exercise training alone (Ex). 12-weeks of supervised exercise-training program was carried out in both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks of treatment.

Results

Cardiopulmonary exercise test showed a significant increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (∆ VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ∆ VO2 MEx +0.19 [0.33 to 0.05] l/min; ∆ VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the MEx (58.3 ± 19 vs 77.3 ± 16; p < 0.01) and Ex (62.1 ± 17 vs 73.7 ± 12; p < 0.005) groups.

Conclusions

We evidenced that cardiopulmonary negative effects showed by MET therapy may be counterbalanced with the combination of exercise training. Given that exercise training associated with MET produced similar effects to exercise training alone in terms of maximal aerobic capacity and HRQoL, programmed exercise training remains the first choice therapy in insulin resistant patients.

【 授权许可】

   
2014 Cadeddu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Reaven GM: Role of insulin resistance in human disease. Banting Lecture 1988 Diab 1988, 37:1595-607.
• [2]Miyatake N, Saito T, Wada J, Miyachi M, Tabata I, Matsumoto S, Nishikawa H, Makino H, Numata T: Comparison of ventilatory threshold and exercise habits between Japanese men with and without metabolic syndrome. Diabetes Res Clin Pract 2007, 77:314-9.
• [3]Ingelsson E, Sundström J, Arnlöv J, Zethelius B, Lind L: Insulin resistance and risk of congestive heart failure. JAMA 2005, 294:334-41.
• [4]Tuunanen H, Knuuti J: Metabolic remodelling in human heart failure. Cardiovasc Res 2011, 90:251-7.
• [5]Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403.
• [6]Rhee MK, Herrick K, Ziemer DC, Vaccarino V, Weintraub WS, Narayan KM, Kolm P, Twombly JG, Phillips LS: Many Americans have pre-diabetes and should be considered for metformin therapy. Diabetes Care 2010, 33:49-54.
• [7]Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B: European Association for Study of Diabetes: medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the study of diabetes. Diabetes Care 2009, 32:193-203.
• [8]Braun B, Eze P, Stephens BR, Hagobian TA, Sharoff CG, Chipkin SR, Goldstein B: Impact of metformin on peak aerobic capacity. Appl Physiol Nutr Metab 2008, 33:61-7.
• [9]Cadeddu C, Nocco S, Deidda M, Cadeddu F, Bina A, Demuru P, Cossu E, Baroni M, Mercuro G: Cardiopulmonary and endothelial effects of metformin treatment in an insulin resistant population. Int J Cardiol 2012, 158:302-4.
• [10]Cadeddu C, Deidda M, Nocco S, Locci E, Cossu E, Baroni M, Atzori L, Mercuro G: Effects of Metformin treatment on Myocardial and Endothelial functionin insulin resistance patients: a metabolomic study. Diabetes Metab 2013, 158:302-4.
• [11]Wong AKF, Symon R, AlZadjali MA, Ang DSC, Ogston S, Choy A, Petrie JR, Struthers AD, Lang CC: The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail 2012, 14:1303-10.
• [12]Malin SK, Gerber R, Chipkin SR, Braun B: Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care 2012, 35:131-6.
• [13]Tapp RJ, Dunstan DW, Phillips P, Tonkin A, Zimmet PZ, Shaw JE, AusDiab Study Group: Association between impaired glucose metabolism and quality of life: results from the Australian diabetes obesity and lifestyle study. Diabetes Res Clin Pract 2006, 74:154-61.
• [14]Taylor LM, Spence JC, Raine K, Plotnikoff RC, Vallance JK, Sharma AM: Physical activity and health-related quality of life in individuals with prediabetes. Diabetes Res Clin Pract 2010, 90:15-21.
• [15]Ackermann RT, Barrett-Connor E, Linda Delahanty MS RD, Saudek CD, Goldberg RB: Impact of lifestyle intervention and metformin on health-related quality of life: the Diabetes Prevention Program Randomized Trial. J Gen Intern Med 2012, 27:1594-1601.
• [16]Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, Alberiche M, Bonadonna RC, Muggeo M: Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998, 47:1643-9.
• [17]Cadeddu C, Nocco S, Deidda M, Cadeddu F, Bina A, Demuru P, Cossu E, Baroni M, Mercuro G: Relationship between high values of HOMA-IR and cardiovascular response to metformin. Int J Cardiol 2012, 167:282.
• [18]Wasserman K, Hansen JE, Sue DY, Whipp BJ: Normal values. In Principles of exercise testing and interpretation. Edited by Lea L. Philadelphia: Lea, Fabiger; 1987:72-85.
• [19]Ware JE, Gandek B, Kosinski M, Aaronson NK, Apolone G, Brazier J, Bullinger M, Kaasa S, Leplège A, Prieto L, Sullivan M, Thunedborg K: The equivalence of SF-36 summary health scores estimated using standard and country-specific algorithms in 10 countries: results from the IQOLA Project International Quality of Life Assessment. J Clin Epidemiol 1998, 51:1167-70.
• [20]Mosconi P, Torri V, Cifani S, Ruggiata R, Meyerowitz BE, Apolone G, Liberati A: The multi-centre assessment of quality of life: the Interdisciplinary Group for Cancer Care Evaluation (GIVIO) experience in Italy. Stat Med 1998, 17:577-85.
• [21]Colberg SR, Albright AL, Blissmer BJ, Braun B, Chasan-Taber L, Fernhall B, Regensteiner JG, Rubin RR, Sigal RJ: American Diabetes Association: exercise and type 2 diabetes: American College of Sports Medicine and the American Diabetes Association: joint position statement. exercise and type 2 diabetes. Med Sci Sports Exerc 2010, 42:2282-303.
• [22]Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE: Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002, 346:793-801.
• [23]Witteles RM, Fowler MB: Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol 2008, 51:93-102.
• [24]Wheatcroft SB, Williams IL, Shah AM, Kearney MT: Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 2003, 20:255-68.
• [25]Cadeddu C, Nocco S, Piano D, Deidda M, Cossu E, Baroni MG, Mercuro G: Early impairment of contractility reserve in patients with insulin resistance in comparison with healthy subjects. Cardiovasc Diabetol 2013, 12:66. BioMed Central Full Text
• [26]Cadeddu C, Nocco S, Piano D, Deidda M, Cossu E, Baroni MG, Mercuro G: Early ventricular dysfunction in type ii diabetes: role of Metabolic Unbalance. J Diab Metab 2013, S13:004.
• [27]Bethel MA, Califf RM: Role of lifestyle and oral anti-diabetic agents to prevent type 2 diabetes mellitus and cardiovascular disease. Am J Cardiol 2007, 99:726-31.
• [28]Dasgupta K, Grover SA, Da Costa D, Lowensteyn I, Yale JF, Rahme E: Impact of modified glucose target and exercise interventions on vascular risk factors. Diabetes Res Clin Pract 2006, 72:53-60.
• [29]Batandier C, Guigas B, Detaille D, El-Mir MY, Fontaine E, Rigoulet M, Leverve XM: The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr 2006, 38:33-42.
• [30]Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, Fontaine E, Wiernsperger NF: Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab 2003, 29:6S88-94.
• [31]Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S: Diabetes Prevention Program Research Group: 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.
• [32]Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Finnish Diabetes Prevention Study Group: prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001, 344:1343-50.
• [33]Love-Osborne K, Sheeder J, Zeitler P: Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr 2008, 152:817-22.
• [34]Snehalatha C, Mary S, Selvam S, Sathish Kumar CK, Shetty SB, Nanditha A, Ramachandran A: Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian diabetes prevention programme-1 (IDPP-1). Diabetes Care 2009, 32:1796-801.
• [35]Sharoff CG, Hagobian TA, Malin SK, Chipkin SR, Yu H, Hirshman MF, Goodyear LJ, Braun B: Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals. Am J Physiol Endocrinol Metab 2010, 298:E815-23.
• [36]Narkar VA: AMPK and PPAR delta agonists are exercise mimetics. Cell 2008, 134:405-15.
• [37]Jadhav S, Ferrell W, Greer IA, Petrie JR, Cobbe SM, Sattar N: Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2006, 48:956-63.
• [38]Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GMC: Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 2005, 258:250-256.