Exercise in type 2 diabetes: Genetic, metabolic and neuromuscular adaptations. A review of the evidence

British Journal of Sports Medicine

Volumn 51, Issue 21, 2017, Pages 1533-1538

  Zanuso, Silvano ^a   Sacchetti, Massimo ^b   Sundberg, Carl Johan ^c   Orlando, Giorgio ^b   Benvenuti, Paolo ^d   Balducci, Stefano ^e  

^a Faculty of Engineering and Computing   (United Kingdom)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c KAROLINSKA INSTITUTE   (Sweden)

^d UNIVERSITY OF VERONA   (Italy)

^e Metabolic Fitness Association   (Italy)

Author keywords

Aerobics; Anaerobic; Diabetes; Exercise Training

Indexed keywords

ADAPTATION; CARDIOVASCULAR DISEASE; EXERCISE; GENETIC EPIGENESIS; HUMAN; INSULIN RESISTANCE; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOPHYSIOLOGY; PHYSIOLOGY; RESISTANCE TRAINING; SKELETAL MUSCLE;

ADAPTATION, PHYSIOLOGICAL; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; EPIGENESIS, GENETIC; EXERCISE; HUMANS; INSULIN RESISTANCE; METABOLISM; MUSCLE, SKELETAL; RESISTANCE TRAINING;

EID: 85026326389     PISSN: 03063674     EISSN: 14730480     Source Type: Journal    
DOI: 10.1136/bjsports-2016-096724     Document Type: Review

References (99)

1. Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
2. Tuomilehto J, Lindström J, Eriksson JG, et al; 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.
3. Colberg SR, Sigal RJ, Fernhall B, et al; American College of Sports Medicine, American Diabetes Association. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 2010;33:e147-e167.
4. Sigal RJ, Kenny GP, Boulè NG, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 2007;147:357-69.
5. Church TS, Blair SN, Cocreham S, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010;304:2253-62.
6. Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011;305:1790-9.
7. Balducci S, Zanuso S, Nicolucci A, et al; Italian Diabetes Exercise Study (IDES) Investigators. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the italian diabetes and exercise study (IDES). Arch Intern Med 2010;170:1794-803.
8. Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013;17:162-84.
9. Strasser B, Pesta D. Resistance training for diabetes prevention and therapy: experimental findings and molecular mechanisms. Biomed Res Int 2013;2013:1-8.
10. Bianchi L, Zuliani G, Volpato S. Physical disability in the elderly with diabetes: epidemiology and mechanisms. Curr Diab Rep 2013;13:824-30.
11. Orlando G, Balducci S, Bazzucchi I, et al. Neuromuscular dysfunction in type 2 diabetes: underlying mechanisms and effect of resistance training. Diabetes Metab Res Rev 2016;32:40-50.
12. Albers PH, Pedersen AJ, Birk JB, et al. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes. Diabetes 2015;64:485-97.
13. Balducci S, Sacchetti M, Orlando G, et al; Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes SAMBA Investigators. Correlates of muscle strength in diabetes: the study on the assessment of determinants of muscle and bone strength abnormalities in diabetes (SAMBA). Nutr Metab Cardiovasc Dis 2014;24:18-26.
14. Sacchetti M, Scotto Sacchetti M, Balducci S, et al. Neuromuscular dysfunction in diabetes: role of nerve impairment and training status. Med Sci Sports Exerc 2013;45:52-9.
15. Bodine SC, Stitt TN, Gonzalez M, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 2001;3:1014-9.
16. Philp A, Hamilton DL, Baar K. Signals mediating skeletal muscle remodeling by resistance exercise: pi3-kinase independent activation of mTORC1. J Appl Physiol 2011;110:561-8.
17. Gustafsson T. Vascular remodelling in human skeletal muscle. Biochem Soc Trans 2011;39:1628-32.
18. Olfert IM, Howlett RA, Wagner PD, et al. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 2010;299:R1059-67.
19. Hood DA, Tryon LD, Vainshtein A, et al. Exercise and the regulation of mitochondrial turnover. Prog Mol Biol Transl Sci 2015;135:99-127.
20. Richter EA, Hargreaves M, Exercise HM. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 2013;93:993-1017.
21. Timmons JA, Larsson O, Jansson E, et al. Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy. FASEB J 2005;19:750-60.
22. Lindholm ME, Marabita F, Gomez-Cabrero D, et al. An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training. Epigenetics 2014;9:1557-69.
23. Perry CG, Lally J, Holloway GP, et al. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol 2010;588:4795-810.
24. Latouche C, Jowett JB, Carey AL, et al. Effects of breaking up prolonged sitting on skeletal muscle gene expression. J Appl Physiol 2013;114:453-60.
25. Gibala MJ, McGee SL, Garnham AP, et al. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol 2009;106:929-34.
26. Sriwijitkamol A, Coletta DK, Wajcberg E, et al. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and doseresponse study. Diabetes 2007;56:836-48.
27. Little JP, Gillen JB, Percival ME, et al. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol 2011;111:1554-60.
28. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74.
29. Keller P, Vollaard NB, Gustafsson T, et al. A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype. J Appl Physiol 2011;110:46-59.
30. Bork-Jensen J, Scheele C, Christophersen DV, et al. Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes. Diabetologia 2015;58:363-73.
31. Barrès R, Yan J, Egan B, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 2012;15:405-11.
32. Rönn T, Ling C. DNA methylation as a diagnostic and therapeutic target in the battle against type 2 diabetes. Epigenomics 2015;7:451-60.
33. Nitert MD, Dayeh T, Volkov P, et al. Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes 2012;61:3322-32.
34. Bouchard C, Antunes-Correa LM, Ashley EA, et al. Personalized preventive medicine: genetics and the response to regular exercise in preventive interventions. Prog Cardiovasc Dis 2015;57:337-46.
35. Vollaard NB, Constantin-Teodosiu D, Fredriksson K, et al. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol 2009;106:1479-86.
36. Bouchard C, An P, Rice T, et al. Familial aggregation of VO2max response to exercise training: results from the HERITAGE family study. J Appl Physiol 1999;87:1003-8.
37. Timmons JA, Jansson E, Fischer H, et al. Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans. BMC Biol 2005;3:19.
38. Timmons JA, Knudsen S, Rankinen T, et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 2010;108:1487-96
39. Bouchard C, Sarzynski MA, Rice TK, et al. Genomic predictors of the maximal O2 uptake response to standardized exercise training programs. J Appl Physiol 2011;110:1160-70.
40. Bouchard C, Blair SN, Church TS, et al. Adverse metabolic response to regular exercise: is it a rare or common occurrence? PLoS One 2012;7:e37887.
41. Pandey A, Swift DL, McGuire DK, et al. Metabolic effects of exercise training among fitness-nonresponsive patients with type 2 diabetes: the HART-D study. Diabetes Care 2015;38:1494-501.
42. Stephens NA, Xie H, Johannsen NM, et al. A transcriptional signature of "exercise resistance" in skeletal muscle of individuals with type 2 diabetes mellitus. Metabolism 2015;64:999-1004.
43. DeFronzo RA, Jacot E, Jequier E, et al. The effect of insulin on the disposal of intravenous glucose. results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 1981;30:1000-7.
44. Janssen I, Heymsfield SB, Wang ZM, et al. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol 2000;89:81-8.
45. Zurlo F, Larson K, Bogardus C, et al. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 1990;86:1423-7.
46. Boulè 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;286:1218-27.
47. Kelley GA, Kelley KS. Effects of aerobic exercise on lipids and lipoproteins in adults with type 2 diabetes: a meta-analysis of randomized-controlled trials. Public Health 2007;121:643-55.
48. Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011;305:1790-9.
49. Zanuso S, Jimenez A, Pugliese G, et al. Exercise for the management of type 2 diabetes: a review of the evidence. Acta Diabetol 2010;47:15-22.
50. Goodyear LJ. AMP-activated protein kinase: a critical signaling intermediary for exercise-stimulated glucose transport? Exerc Sport Sci Rev 2000;28:113-6.
51. Trevellin E, Scorzeto M, Olivieri M, et al. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOSdependent mechanisms. Diabetes 2014;63:2800-11.
52. Meex RC, Schrauwen-Hinderling VB, Moonen-Kornips E, et al. Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity. Diabetes 2010;59:572-9.
53. Roden M. Exercise in type 2 diabetes: to resist or to endure? Diabetologia 2012;55:1235-9.
54. Yaspelkis BB. Resistance training improves insulin signalling and action in skeletal muscle. Exerc Sport Sci Rev 2006;33:42-6.
55. Kuk JL, Kilpatrick K, Davidson LE, et al. Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women. Appl Physiol Nutr Metab 2008;33:769-74.
56. Schiaffino S, Mammucari C. Regulation of skeletal muscle growth by the IGF1-Akt/ PKB pathway: insights from genetic models. Skelet Muscle 2011;1:4.
57. Case N, Thomas J, Sen B, et al. Mechanical regulation of glycogen synthase kinase 3? (GSK3?) in mesenchymal stem cells is dependent on akt protein serine 473 phosphorylation via mTORC2 protein. J Biol Chem 2011;286:39450-6.
58. Putman CT, Jones NL, Hultman E, et al. Effects of short-term submaximal training in humans on muscle metabolism in exercise. Am J Physiol 1998;275:132-9.
59. Cline GW, Petersen KF, Krssak M, et al. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med 1999;341:240-6.
60. Hayashi T, Hirshman MF, Kurth EJ, et al. Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998;47:1369-73.
61. Dreyer HC, Fujita S, Cadenas JG, et al. Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol 2006;576:613-24.
62. Mu J, Brozinick JT, Valladares O, et al. A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 2001;7:1085-94.
63. Wilson JM, Loenneke JP, Jo E, et al. The effects of endurance, strength, and power training on muscle fiber type shifting. J Strength Cond Res 2012;26:1724-9.
64. Gregg EW, Beckles GL, Williamson DF, et al. Diabetes and physical disability among older U.S. adults. Diabetes Care 2000;23:1272-7.
65. Sayer AA, Dennison EM, Syddall HE, et al. Type 2 diabetes, muscle strength, and impaired physical function: the tip of the iceberg? Diabetes Care 2005;28:2541-2.
66. Andersen H, Stålberg E, Gjerstad MD, et al. Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy. Muscle Nerve 1998;21:1647-54.
67. Ramji N, Toth C, Kennedy J, et al. Does diabetes mellitus target motor neurons? Neurobiol Dis 2007;26:301-11.
68. Allen MD, Choi IH, Kimpinski K, et al. Motor unit loss and weakness in association with diabetic neuropathy in humans. Muscle Nerve 2013;48:298-300.
69. Fahim MA, Hasan MY, Alshuaib WB. Early morphological remodeling of neuromuscular junction in a murine model of diabetes. J Appl Physiol 2000;89:2235-40.
70. Andersen H, Poulsen PL, Mogensen CE, et al. Isokinetic muscle strength in long-term IDDM patients in relation to diabetic complications. Diabetes 1996;45:440-5.
71. Kalyani RR, Tra Y, Yeh HC, et al. Quadriceps strength, quadriceps power, and gait speed in older U.S. adults with diabetes mellitus: results from the national health and nutrition examination survey, 1999-2002. J Am Geriatr Soc 2013;61:769-75.
72. Bittel DC, Bittel AJ, Tuttle LJ, et al. Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy. J Diabetes Complications 2015;29:250-7.
73. Volpato S, Bianchi L, Lauretani F, et al. Role of muscle mass and muscle quality in the association between diabetes and gait speed. Diabetes Care 2012;35:1672-9.
74. Moore CW, Allen MD, Kimpinski K, et al. Reduced skeletal muscle quantity and quality in patients with diabetic polyneuropathy assessed by magnetic resonance imaging. Muscle Nerve 2016;53:726-32.
75. Rabøl R, Larsen S, Højberg PM, et al. Regional anatomic differences in skeletal muscle mitochondrial respiration in type 2 diabetes and obesity. J Clin Endocrinol Metab 2010;95:857-63.
76. Olsen DB, Sacchetti M, Dela F, et al. Glucose clearance is higher in arm than leg muscle in type 2 diabetes. J Physiol 2005;565:555-62.
77. Allen MD, Kimpinski K, Doherty TJ, et al. Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure. J Appl Physiol 2015;118:1014-22.
78. Ijzerman TH, Schaper NC, Melai T, et al. Lower extremity muscle strength is reduced in people with type 2 diabetes, with and without polyneuropathy, and is associated with impaired mobility and reduced quality of life. Diabetes Res Clin Pract 2012;95:345-51.
79. Park SW, Goodpaster BH, Lee JS, et al. Health, Aging, and Body Composition Study. Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 2009;32:1993-7.
80. Leenders M, Verdijk LB, van der Hoeven L, et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14:585-92.
81. Andreassen CS, Jakobsen J, Ringgaard S, et al. Accelerated atrophy of lower leg and foot muscles-a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI). Diabetologia 2009;52:1182-91.
82. Segerström ÅB, Elgzyri T, Eriksson KF, et al. Exercise capacity in relation to body fat distribution and muscle fibre distribution in elderly male subjects with impaired glucose tolerance, type 2 diabetes and matched controls. Diabetes Res Clin Pract 2011;94:57-63.
83. Castaneda C, Layne JE, Munoz-Orians L, et al. A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes. Diabetes Care 2002;25:2335-41.
84. Cauza E, Hanusch-Enserer U, Strasser B, et al. The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus. Arch Phys Med Rehabil 2005;86:1527-33.
85. Larose J, Sigal RJ, Khandwala F, et al. Comparison of strength development with resistance training and combined exercise training in type 2 diabetes. Scand J Med Sci Sports 2012;22:e45-e54.
86. Baldi JC, Snowling N. Resistance training improves glycaemic control in obese type 2 diabetic men. Int J Sports Med 2003;24:419-23.
87. Colberg SR, Parson HK, Nunnold T, et al. Effect of an 8-week resistance training program on cutaneous perfusion in type 2 diabetes. Microvasc Res 2006;71:121-7.
88. Tofthagen C, Visovsky C, Berry DL. Strength and balance training for adults with peripheral neuropathy and high risk of fall: current evidence and implications for future research. Oncol Nurs Forum 2012;39:E416-E424.
89. Handsaker JC, Brown SJ, Bowling FL, et al. Resistance exercise training increases lower limb speed of strength generation during stair ascent and descent in people with diabetic peripheral neuropathy. Diabet Med 2016;33:97-104.
90. Kruse RL, Lemaster JW, Madsen RW. Fall and balance outcomes after an intervention to promote leg strength, balance, and walking in people with diabetic peripheral neuropathy: Feet first randomized controlled trial. Phys Ther 2010;90:1568-79.
91. Holten MK, Zacho M, Gaster M, et al. Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes 2004;53:294-305.
92. Brooks N, Layne JE, Gordon PL, et al. Strength training improves muscle quality and insulin sensitivity in hispanic older adults with type 2 diabetes. Int J Med Sci 2006;4:19-27.
93. Gordon PL, Vannier E, Hamada K, et al. Resistance training alters cytokine gene expression in skeletal muscle of adults with type 2 diabetes. Int J Immunopathol Pharmacol 2006;19:739-49.
94. Wang Y, Simar D, Fiatarone Singh MA. Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review. Diabetes Metab Res Rev 2009;25:13-40.
95. Reid KF, Fielding RA. Skeletal muscle power: a critical determinant of physical functioning in older adults. Exerc Sport Sci Rev 2012;40:4-12.
96. Ibáñez J, Gorostiaga EM, Alonso AM, et al. Lower muscle strength gains in older men with type 2 diabetes after resistance training. J Diabetes Complications 2008;22:112-8.
97. Mavros Y, Kay S, Anderberg KA, et al. Changes in insulin resistance and HbA1c are related to exercise-mediated changes in body composition in older adults with type 2 diabetes: interim outcomes from the GREAT2DO trial. Diabetes Care 2013;36:2372-9.
98. Mavros Y, Kay S, Simpson KA, et al. Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training. J Cachexia Sarcopenia Muscle 2014;5:111-20.
99. Larose J, Sigal RJ, Boulè NG, et al. Effect of exercise training on physical fitness in type II diabetes mellitus. Med Sci Sports Exerc 2010;42:1439-47.