Acta Diabetologica

, Volume 53, Issue 6, pp 879–889 | Cite as

Muscle dysfunction in type 2 diabetes: a major threat to patient’s mobility and independence

  • Lara Bianchi
  • Stefano VolpatoEmail author
Review Article


Type 2 diabetes, a common metabolic disease in older people, is a major risk factor for functional limitation, impaired mobility, and loss of independence. In older people, the pathogenesis of functional limitation and disability is complex and multifactorial. A number of potential pathways are involved including cardiovascular disease, peripheral neuropathy, overweight, osteoarthritis, visual deficit, and cognitive impairment, conditions that are all more prevalent among patients with diabetes. Sarcopenia, a geriatric condition characterized by a progressive and generalized loss of skeletal muscle mass and strength, is also involved in the pathogenesis of functional limitations and disability. Recent research has shown that older patients with type 2 diabetes are often affected by skeletal muscle impairment, leading to reduced muscle strength and physical function. Insulin resistance, hyperglycemia, muscle fat infiltration, and peripheral neuropathies are hypothesized as the fundamental biological mechanisms leading to muscle impairment in people with diabetes. This review summarizes the current literature on the biological pathways responsible for skeletal muscle dysfunction in type 2 diabetes and analyzes the role of decline in muscle strength and quality on the association between diabetes and mobility disability.


Diabetes Muscle mass Muscle strength Disability Aging 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All procedures were in accordance with the ethical standards of the institutional research committee and with the Helsinky Declaration.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, informed consent is not required.


  1. 1.
    Danaei G, Finucane MM, Lu Y et al (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 378:31–40CrossRefPubMedGoogle Scholar
  2. 2.
    Guariguata L, Whiting DR, Hambleton I et al (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149CrossRefPubMedGoogle Scholar
  3. 3.
    Expert Canadian Diabetes Association Clinical Practice Guidelines, Goldenberg R, Punthakee Z (2013) Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes 37(Suppl 1):S8–S11Google Scholar
  4. 4.
    Bianchi L, Zuliani G, Volpato S (2013) Physical disability in the elderly with diabetes: epidemiology and mechanisms. Curr Diabetes Rep 13:824–830CrossRefGoogle Scholar
  5. 5.
    Kirkman MS, Briscoe VJ, Clark N et al (2012) Diabetes in older adults. Diabetes Care 35:2650–2664CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Volpato S, Blaum C, Resnick H et al (2002) Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women’s Health and Aging study. Diabetes Care 25:678–683CrossRefPubMedGoogle Scholar
  7. 7.
    Volpato S, Bianchi L, Lauretani F et al (2012) Role of muscle mass and muscle quality in the association between diabetes and gait speed. Diabetes Care 35:1672–1679CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Goodpaster BH, Krishnaswami S, Resnick H et al (2003) Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26(2):372–379CrossRefPubMedGoogle Scholar
  9. 9.
    Gallagher D, Kelley DE, Yim JE et al (2009) Adipose tissue distribution is different in type 2 diabetes. Am J Clin Nutr 89:807–814CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Park SW, Goodpaster BH, Strotmeyer ES et al (2006) Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes 55:1813–1818CrossRefPubMedGoogle Scholar
  11. 11.
    Heshka S, Ruggiero A, Bray GA et al (2008) Altered body composition in type 2 diabetes mellitus. Int J Obes (Lond) 32:780–787CrossRefGoogle Scholar
  12. 12.
    Kim TN, Park MS, Yang SJ et al (2010) Prevalence and determinant factors of sarcopenia in patients with type 2 diabetes: the Korean sarcopenic obesity study (KSOS). Diabetes Care 33:1497–1499CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kalyani RR, Metter EJ, Ramachandran R et al (2012) Glucose and insulin measurements from the oral glucose tolerance test and relationship to muscle mass. J Gerontol A Biol Sci Med Sci 67:74–81CrossRefPubMedGoogle Scholar
  14. 14.
    Lee JSW, Auyeung TW, Leung J et al (2010) The effect of diabetes mellitus on age-associated lean mass loss in 3153 older adults. Diabetes Med 27:1366–1371CrossRefGoogle Scholar
  15. 15.
    Park SW, Goodpaster BH, Lee JS et al (2011) Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 32:1993–1997CrossRefGoogle Scholar
  16. 16.
    Lee CG, Boyko EJ, Barrett-Connor E et al (2011) Insulin sensitizers may attenuate lean mass loss in older men with diabetes. Diabetes Care 34:2381–2386CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Clark BC, Manini TM (2008) Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci 63:829–834CrossRefPubMedGoogle Scholar
  18. 18.
    Park SW, Goodpaster BH, Strotmeyer ES et al (2007) Accelerated loss of skeletal muscle strength in older adults with type diabetes: the health, aging, and body composition study. Diabetes Care 30:1507–1512CrossRefPubMedGoogle Scholar
  19. 19.
    Barzilay JI, Cotsonis GA, Walston J et al (2009) Insulin resistance is associated with decreased quadriceps muscle strength in nondiabetic adults aged > or = 70 years. Diabetes Care 32:736–738CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kalyani RR, Tra Y, Yeh HC et al (2013) Quadriceps strength, quadriceps power, and gait speed in older US. adults with diabetes mellitus: results from the national health and nutrition examination survey, 1999–2002. J Am Geriatr Soc 61:769–775CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    van der Kooi AL, Snijder MB, Peters RJ et al (2015) The association of handgrip strength and type 2 diabetes mellitus in six ethnic groups: an analysis of the HELIUS study. PLoS One 10(9):e0137739CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Andersen H, Nielsen S, Mogensen CE et al (2004) Muscle strength in type 2 diabetes. Diabetes 53:1543–1548CrossRefPubMedGoogle Scholar
  23. 23.
    Lee CG, Schwartz AV, Yaffe K et al (2013) Changes in physical performance in older women according to presence and treatment of diabetes mellitus. J Am Geriatr Soc 61:1872–1878CrossRefPubMedGoogle Scholar
  24. 24.
    Sayer AA, Dennison EM, Syddall HE et al (2005) Type 2 diabetes, muscle strength, and impaired physical function: the tip of the iceberg? Diabetes Care 28:2541–2542CrossRefPubMedGoogle Scholar
  25. 25.
    Leenders M, Verdijk LB, van der Hoeven L et al (2013) Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 14:585–592CrossRefPubMedGoogle Scholar
  26. 26.
    Kalyani RR, Metter EJ, Egan J et al (2015) Hyperglycemia predicts persistently lower muscle strength with aging. Diabetes Care 38:82–90CrossRefPubMedGoogle Scholar
  27. 27.
    Orlando G, Balducci S, Bazzucchi I et al (2016) Neuromuscular dysfunction in type 2 diabetes: underlying mechanisms and effect of resistance training. Diabetes Metab Res Rev 32:40–50CrossRefPubMedGoogle Scholar
  28. 28.
    Abbatecola AM, Ferrucci L, Ceda G et al (2005) Insulin resistance and muscle strength in older persons. J Gerontol A Biol Sci Med Sci 60(10):1278–1282CrossRefPubMedGoogle Scholar
  29. 29.
    Reggiani C, Schiaffino S (2011) Fiber types in mammalian skeletal muscles. Physiol Rev 91(4):1447–1531CrossRefPubMedGoogle Scholar
  30. 30.
    Gaster M, Staehr P, Beck-Nielsen H et al (2001) GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease? Diabetes 50:1324–1329CrossRefPubMedGoogle Scholar
  31. 31.
    Gaster M, Poulsen P, Handberg A et al (2000) Direct evidence of fibertype dependent GLUT-4 expression in human skeletal muscle. Am J Physiol 278:E910–E916Google Scholar
  32. 32.
    Lexell J (1995) Human aging, muscle mass, and fiber type composition. J Gerontol A Biol Sci Med Sci 50:11–16PubMedGoogle Scholar
  33. 33.
    Kuo CK, Lin LY, Yu YH et al (2009) Inverse association between insulin resistance and gait speed in nondiabetic older men: results from the US. national health and nutrition examination survey (NHANES) 1999–2002. BMC Geriatr 9:49CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kalyani RR, Varadhan R, Weiss CO et al (2012) Frailty status and altered glucose-insulin dynamics. J Gerontol A Biol Sci Med Sci 67:1300–1306CrossRefPubMedGoogle Scholar
  35. 35.
    Kalyani RR, Corriere M, Ferrucci L (2014) Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol 2:819–829CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kaushik S, Singh R, Cuervo AM (2010) Autophagic pathways and metabolic stress. Diabetes Obes Metab 12(suppl 2):4–14CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Phielix E, Mensink M (2008) Type 2 diabetes mellitus and skeletal muscle metabolic function. Physiol Behav 94:252–258CrossRefPubMedGoogle Scholar
  38. 38.
    Simoneau JA, Bouchard C (1989) Human variation in skeletal muscle fiber-type proportion and enzyme activities. Am J Physiol Endocrinol Metab 257:E567–E572Google Scholar
  39. 39.
    Simoneau JA, Bouchard C (1995) Genetic determinism of fiber type proportion in human skeletal muscle. FASEB J 9:1091–1095PubMedGoogle Scholar
  40. 40.
    Kelley DE, He J, Menshikova EV et al (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950CrossRefPubMedGoogle Scholar
  41. 41.
    Ramamurthy B, Höök P, Jones AD et al (2001) Changes in myosin structure and function in response to glycation. FASEB J 15:2415–2422CrossRefPubMedGoogle Scholar
  42. 42.
    Hilton TN, Tuttle LJ, Bohnert KL et al (2008) Excessive adipose tissue infiltration in skeletal muscle in individuals with obesity, diabetes mellitus, and peripheral neuropathy: association with performance and function. Phys Ther 88:1336–1344CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Goodpaster BH, Carlson CL, Visser M et al (2001) Attenuation of skeletal muscle and strength in the elderly: the Health ABC study. J Appl Physiol 90:2157–2165PubMedGoogle Scholar
  44. 44.
    Goodpaster BH, Thaete FL, Kelley DE (2000) Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 71:885–892PubMedGoogle Scholar
  45. 45.
    Visser M, Goodpaster BH, Kritchevsky SB et al (2005) Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well functioning older persons. J Gerontol A Biol Sci Med Sci 60:324–333CrossRefPubMedGoogle Scholar
  46. 46.
    Pedersen M, Bruunsgaard H, Weis N et al (2003) Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev 124:495–502CrossRefPubMedGoogle Scholar
  47. 47.
    Abbatecola AM, Ferrucci L, Grella R et al (2004) Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly. J Am Geriatr Soc 52(3):399–404CrossRefPubMedGoogle Scholar
  48. 48.
    Fiorentino TV, Hribal ML, Perticone M et al (2015) Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the american diabetes association criteria. Acta Diabetol 52(2):349–356CrossRefPubMedGoogle Scholar
  49. 49.
    Hotamisligil GS (1999) The role of TNF-alpha and TNF receptors in obesity and insulin resistance. J Intern Med 245:621–625CrossRefPubMedGoogle Scholar
  50. 50.
    Bastard JP, Maachi M, Van Nhieu JT et al (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87(5):2084–2089CrossRefPubMedGoogle Scholar
  51. 51.
    Meng SJ, Yu LJ (2010) Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 11:1509–1526CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Booth FW, Laye MJ, Roberts MD (2011) Lifetime sedentary living accelerates some aspects of secondary aging. J Appl Physiol 111:1497–1504CrossRefPubMedGoogle Scholar
  53. 53.
    Hamasaki H, Kawashima Y, Adachi H et al (2015) Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes. Peer J 3:e942CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Sigal RJ, Kenny GP, Wasserman DH et al (2006) Physical activity/exercise and type 2 diabetes: a consensus statement from the american diabetes association. Diabetes Care 29:1433–1438CrossRefPubMedGoogle Scholar
  55. 55.
    Umpierre D, Ribeiro PA, Kramer CK et al (2011) Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 305:1790–1799CrossRefPubMedGoogle Scholar
  56. 56.
    Fagour C, Gonzalez C, Pezzino S et al (2013) Low physical activity in patients with type 2 diabetes: the role of obesity. Diabetes Metab 39:85–87CrossRefPubMedGoogle Scholar
  57. 57.
    Cesari M, Penninx BW, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sc 59:242–248CrossRefGoogle Scholar
  58. 58.
    Manini TM, Clark BC, Nalls MA et al (2007) Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr 85:377–384PubMedGoogle Scholar
  59. 59.
    Tresierras MA, Balady GJ (2009) Resistance training in the treatment of diabetes and obesity: mechanisms and outcomes. J Cardiopulm Rehabil Prev 29(2):67–75CrossRefPubMedGoogle Scholar
  60. 60.
    McGinley SK, Armstrong MJ, Boulé NG et al (2015) Effects of exercise training using resistance bands on glycaemic control and strength in type 2 diabetes mellitus: a metaanalysis of randomised controlled trials. Acta Diabetol 52(2):221–230CrossRefPubMedGoogle Scholar
  61. 61.
    McDermott MM, Guralnik JM, Albay M et al (2004) Impairments of muscles and nerves associated with peripheral arterial disease and their relationship with lower extremity functioning: the InCHIANTI study. J Am Geriatr Soc 52:405–410CrossRefPubMedGoogle Scholar
  62. 62.
    Abbatecola AM, Chiodini P, Gallo C et al (2012) Pulse wave velocity is associated with muscle mass decline: Health ABC study. Age (Dordr) 34(2):469–478CrossRefGoogle Scholar
  63. 63.
    Suzuki E, Kashiwagi A, Nishio Y et al (2001) Increased arterial wall stiffness limits flow volume in the lower extremities in type 2 diabetic patients. Diabetes Care 24:2107–2114CrossRefPubMedGoogle Scholar
  64. 64.
    Womack L, Peters D, Barrett EJ et al (2009) Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications. J Am Coll Cardiol 53:2175–2183CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Resnick HE, Vinik AI, Schwartz AV et al (2000) Independent effects of peripheral nerve dysfunction on lower-extremity physical function in old age. The Women’s Health and Aging study. Diabetes Care 23:1642–1647CrossRefPubMedGoogle Scholar
  66. 66.
    Van Deursen RW, Simoneau GG (1999) Foot and ankle sensory neuropathy, proprioception, and postural stability. J Orthop Sports Phys Ther 29:718–726CrossRefPubMedGoogle Scholar
  67. 67.
    Volpato S, Leveille SG, Blaum C et al (2005) Risk factors for falls in older disabled women with diabetes: The Women’s Health and Aging Study. J Gerontol A Biol Sci Med Sci 60(12):1539–1545CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Bild DE, Selby JV, Sinnock P et al (1989) Lower-extremity amputation in people with diabetes: epidemiology and prevention. Diabetes Care 12:24–31CrossRefPubMedGoogle Scholar
  69. 69.
    Andreassen CS, Jakobsen J, Ringgaard S et al (2009) Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI). Diabetologia 52:1182–1191CrossRefPubMedGoogle Scholar
  70. 70.
    Andersen H, Poulsen PL, Mogensen CE et al (1996) Isokinetic muscle strength in long-term IDDM patients in relation to diabetic complications. Diabetes 45:440–445CrossRefPubMedGoogle Scholar
  71. 71.
    Andreassen CS, Jakobsen J, Ringgaard S et al (2009) Muscle weakness: a progressive late complication in diabetic distal symmetric polyneuropathy. Diabetes 55:806–812CrossRefGoogle Scholar
  72. 72.
    de Rekeneire N, Volpato S (2015) Physical function and disability in older adults with diabetes. Clin Geriatr Med 31:51–65CrossRefPubMedGoogle Scholar
  73. 73.
    Wong E, Backholer K, Gearon E et al (2013) Diabetes and risk of physical disability in adults: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 1:106–114CrossRefPubMedGoogle Scholar
  74. 74.
    Kalyani RR, Saudek CD, Brancati FL et al (2010) Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination survey (NHANES), 1999–2006. Diabetes Care 33:1055–1060CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Volpato S, Ferrucci L, Blaum C et al (2003) Progression of lower-extremity disability in older women with diabetes: The Women’s Health and Aging study. Diabetes Care 26:70–75CrossRefPubMedGoogle Scholar
  76. 76.
    Al Snih S, Fisher MN, Raji MA et al (2005) Diabetes mellitus and incidence of lower body disability among older mexican americans. J Gerontol A Biol Sci Med Sci 60A:1152–1156CrossRefGoogle Scholar
  77. 77.
    Bossoni S, Mazziotti G, Gazzaruso C et al (2008) Relationship between instrumental activities of daily living and blood glucose control in elderly subjects with type 2 diabetes. Age Ageing 37:222–225CrossRefPubMedGoogle Scholar
  78. 78.
    van Sloten TT, Savelberg HH, Duimel-Peeters IG et al (2011) Peripheral neuropathy, decreased muscle strength andobesity arestrongly associated with walking in persons with type 2 diabetes without manifest mobility limitations. Diabetes Res Clin Pract 91:32–39CrossRefPubMedGoogle Scholar
  79. 79.
    Fritschi C, Quinn L (2010) Fatigue in patients with diabetes: a review. J Psychosom Res 69:33–41CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Shah S, Sonawane P, Nahar P et al (2011) Are we ignoring diabetic disability: a cross sectional study of diabetic myopathy. Indian J Med Sci 65:186–192CrossRefPubMedGoogle Scholar
  81. 81.
    Sénéchal M, Johannsen NM, Swift DL (2015) Association between changes in muscle quality with exercise training and changes in cardiorespiratory fitness measures in individuals with type 2 diabetes mellitus: results from the HART-D study. PLoS One 10(8):e0135057CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Pahor M, Guralnik JM, Ambrosius WT et al (2014) Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311:2387–2396CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia 2016

Authors and Affiliations

  1. 1.Department of Medical ScienceUniversity of FerraraFerraraItaly

Personalised recommendations