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Fatigue in Adults with Type 2 Diabetes— An Overview of Current Understanding and Management Approaches

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Published Online: Sep 14th 2012 US Endocrinology, 2012;8(2):84-87 DOI:
Authors: Cynthia Fritschi, Anne M Fink
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Patients with type 2 diabetes often experience fatigue, which impacts their self-care and quality of life. There are few data supporting a relationship between fatigue and glucose homeostasis, but fatigue in type 2 diabetes has been associated with higher body mass index (BMI), depression, physical inactivity, sleep disturbances, and chronic low-grade inflammation. Although links between fatigue and inflammation are documented in other disease populations, little is known about inflammatory mechanisms specific to type 2 diabetes and associated treatment modalities for type 2 diabetes-related fatigue. Herein we review existing knowledge about fatigue in type 2 diabetes and potential pharmacologic and behavioral therapies.


Type 2 diabetes, fatigue, inflammation, patient-reported outcomes, symptoms, management


Patients with type 2 diabetes commonly experience fatigue, which may be incapacitating and adversely affect self-care regimens.1–7 Fatigue is a perplexing problem for healthcare providers.8 Wessely suggests that because fatigue is a non-specific and universal symptom, chronic fatigue is challenging to diagnose and treat.9 Fatigue researchers do not have a standardized definition, measurement approach, or diagnostic criteria. Diabetes-related fatigue is assumed to correlate with alterations in glucose homeostasis, but few data support this hypothesis.3,7,10,11 Fatigue in type 2 diabetes is associated with higher body mass index (BMI),1,7,12 the presence of comorbid conditions,7,13 depression,7 physical inactivity,1,7,14 sleep disturbances,1,15,16 and elevated cytokines.3,10 Fritschi and Quinn recently provided a detailed review of the correlates of fatigue in diabetes, including conflicting findings regarding the relationship between fatigue and glycemic control.8

Type 2 diabetes is a disorder associated with chronic low-grade inflammation.17,18 Type 2 diabetes and insulin resistance, especially among obese patients, were linked to an increased production of pro-inflammatory cytokines (e.g., tumour necrosis factor alpha [TNF-α], monocyte chemoattractant protein-1 [MCP-1], interleukin-1β [IL-1β], interleukin-6 [IL-6]) from immune cells as well as increased acute phase reactants (e.g., C-reactive protein [CRP]). Pro-inflammatory cytokines and CRP were associated with high fatigue levels10,11,19,20 and depression and sleep disturbances in a variety of diseases.21–24 There is a considerable gap in the literature, however, about the treatment of fatigue secondary to type 2 diabetes. Anti-inflammatory therapies may ameliorate fatigue with type 2 diabetes. Thus, our discussion of fatigue interventions will focus on the few available pharmacologic and behavioral interventions in patients with type 2 diabetes to impact inflammation and fatigue.

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The authors have no conflicts of interest to declare.


Cynthia Fritschi, PhD, RN, University of Illinois at Chicago College of Nursing (MC 802), 845 South Damen Avenue, Chicago, IL 60612, US. E:


Type 2 diabetes, fatigue, inflammation, patient-reported outcomes, symptoms, management




  1. Grandner MA, Patel NP, Perlis ML, et al., Obesity, diabetes, and exercise associated with sleep-related complaints in the American population, J Public Health, 2011;19:463–74.
  2. Weijman I, Ros WJ, Rutten GE, et al., Fatigue in employees with diabetes: Its relation with work characteristics and diabetes related burden, Occup Environ Med, 2003;60(Suppl. 1):i93–8.
  3. Cavelti-Weder C, Furrer R, Keller C, et al., Inhibition of IL-1beta improves fatigue in type 2 diabetes, Diabetes Care, 2011;34(10):e158.
  4. Adriaanse MC, Dekker JM, Spijkerman AM, et al., Health-related quality of life in the first year following diagnosis of type 2 diabetes: Newly diagnosed patients in general practice compared with screening-detected patients. The Hoorn Screening Study, Diabet Med, 2004;21(10):1075–81.
  5. Garcia AA, Symptom prevalence and treatments among Mexican Americans with type 2 diabetes, Diabetes Educ, 2005;31(4):543–54.
  6. Warren RE, Deary IJ, Frier BM, The symptoms of hyperglycaemia in people with insulin-treated diabetes: Classification using principal components analysis, Diabetes Metab Res, 2003;19(5):408–14.
  7. Fritschi C, Quinn L, Hacker ED, et al., Fatigue in women with type 2 diabetes, Diabetes Educ, 2012;38(5):662–72.
  8. Fritschi C, Quinn L, Fatigue in patients with diabetes: A review, J Psychosom Res, 2010;69(1):33–41.
  9. Wessely S, The epidemiology of chronic fatigue syndrome, Epidemiol Psichiatr Soc, 1998;7(1):10–24.
  10. Lasselin J, Laye S, Dexpert S, et al., Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes, Brain Behav Immun, 2012;26(8):1211–9.
  11. Lasselin J, Layé S, Barreau J, et al., Fatigue and cognitive symptoms in patients with diabetes: Relationship with disease phenotype and insulin treatment. Psychoneuroendocrinology, 2012;37(9):1468–78.
  12. Hlatky MA, Chung SC, Escobedo J, et al., The effect of obesity on quality of life in patients with diabetes and coronary artery disease, Am Heart J, 2010;159(2):292–300.
  13. Weijman I, Kant I, Swaen GM, et al., Diabetes, employment and fatigue-related complaints: A comparison between diabetic employees, "healthy" employees, and employees with other chronic diseases, J Occup Environ Med, 2004;46(8):828–36.
  14. Thomas N, Alder E, Leese GP, Barriers to physical activity in patients with diabetes, Postgrad Med J, 2004;80(943):287–91.
  15. Chasens ER, Olshansky E, Daytime sleepiness, diabetes, and psychological well-being, Issues Ment Health Nurs, 2008;29(10):1134–50.
  16. Cuellar NG, Ratcliffe SJ, A comparison of glycemic control, sleep, fatigue, and depression in type 2 diabetes with and without restless legs syndrome, J Clin Sleep Med, 2008;4(1):50–6.
  17. Alexandraki KI, Piperi C, Ziakas PD, et al., Cytokine secretion in long-standing diabetes mellitus type 1 and 2: Associations with low-grade systemic inflammation, J Clin Immunol, 2008;28(4):314–21.
  18. Baris N, Erdogan M, Sezer E, et al., Alterations in L-arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria, Acta Diabetol, 2009;46(4):309–16.
  19. Pickup JC, Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes, Diabetes Care, 2004;27(3):813–23.
  20. Luotola K, Pietila A, Zeller T, et al., Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes, J Intern Med, 2011;269(3):322–32.
  21. Mills PJ, Natarajan L, von Kanel R, et al., Diurnal variability of C-reactive protein in obstructive sleep apnea, Sleep Breath, 2009;13(4):415–20.
  22. Yue HJ, Mills PJ, Ancoli-Israel S, et al., The roles of TNF-alpha and the soluble TNF receptor I on sleep architecture in OSA, Sleep Breath, 2009;13(3):263–9.
  23. Dantzer R, Capuron L, Irwin MR, et al., Identification and treatment of symptoms associated with inflammation in medically ill patients, Psychoneuroendocrinology, 2008;33(1):18–29.
  24. Dantzer R, Cytokine, sickness behavior, and depression, Neurol Clin, 2006;24(3):441–60.
  25. Krishnan R, Cella D, Leonardi C, et al., Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks, Br J Dermatol, 2007;157(6):1275–7.
  26. Gniadecki R, Robertson D, Molta CT, et al., Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens, J Eur Acad Dermatol Venereol, 2012;26(11):1436–43.
  27. Gladman DD, Bombardier C, Thorne C, et al., Effectiveness and safety of etanercept in patients with psoriatic arthritis in a Canadian clinical practice setting: The REPArE trial, J Rheumatol, 2011;38(7):1355–62.
  28. Strand V, Singh JA, Improved health-related quality of life with effective disease-modifying antirheumatic drugs: Evidence from randomized controlled trials, Am J Manag Care, 2008;14(4):234–54.
  29. Valentine RJ, Woods JA, McAuley E, et al., The associations of adiposity, physical activity and inflammation with fatigue in older adults, Brain Behav Immun, 2011;25(7):1482–90.
  30. Resnick HE, Carter EA, Aloia M, Phillips B, Cross-sectional relationship of reported fatigue to obesity, diet, and physical activity: Results from the third national health and nutritional examination survey, JCSM, 2006;2(2):163–9.
  31. Anandacoomarasamy A, Caterson ID, Leibman S, et al., Influence of BMI on health-related quality of life: Comparison between an obese adult cohort and age-matched population norms, Obesity (Silver Spring), 2009;17(11):2114–8.
  32. Vgontzas AN, Papanicolaou DA, Bixler EO, et al., Sleep apnea and daytime sleepiness and fatigue: Relation to visceral obesity, insulin resistance, and hypercytokinemia, J Clin Endocrinol Metab, 2000;85(3):1151–8.
  33. Chung SC, Hlatky MA, Stone RA, et al., Body mass index and health status in the bypass angioplasty revascularization investigation 2 diabetes trial (BARI 2D), Am Heart J, 2011;162(1):184–92.
  34. Vgontzas AN, Bixler EO, Chrousos GP, Obesity-related sleepiness and fatigue: The role of the stress system and cytokines, Ann N Y Acad Sci, 2006;1083:329–44.
  35. Lim W, Hong S, Nelesen R, Dimsdale JE, The association of obesity, cytokine levels, and depressive symptoms with diverse measures of fatigue in healthy subjects, Arch Intern Med, 2005;165(8):910–5.
  36. Oeser A, Chung CP, Asanuma Y, et al., Obesity is an independent contributor to functional capacity and inflammation in systemic lupus erythematosus, Arthritis Rheum, 2005;52(11):3651–9.
  37. Harford KA, Reynolds CM, McGillicuddy FC, Roche HM, Fats, inflammation and insulin resistance: Insights to the role of macrophage and T-cell accumulation in adipose tissue, Proc Nutr Soc, 2011;70(4):408–17.
  38. Kelly KR, Haus JM, Solomon TP, et al., A low-glycemic index diet and exercise intervention reduces TNF(alpha) in isolated mononuclear cells of older, obese adults, J Nutr, 2011;141(6):1089–94.
  39. King DE, Mainous AG, 3rd, Egan BM, et al., Fiber and C-reactive protein in diabetes, hypertension, and obesity, Diabetes Care, 2005;28(6):1487–9.
  40. Esposito K, Pontillo A, Di Palo C, et al., Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: A randomized trial, JAMA, 2003;289(14):1799–804.
  41. Tsitouras PD, Gucciardo F, Salbe AD, et al., High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults, Horm Metab Res, 2008;40(3):199–205.
  42. Azadbakht L, Atabak S, Esmaillzadeh A, Soy protein intake, cardiorenal indices, and C-reactive protein in type 2 diabetes with nephropathy: A longitudinal randomized clinical trial, Diabetes Care, 2008;31(4):648–54.
  43. Azadbakht L, Esmaillzadeh A, Red meat intake is associated with metabolic syndrome and the plasma C-reactive protein concentration in women, J Nutr, 2009;139(2):335–9.
  44. Khoo J, Piantadosi C, Duncan R, et al., Comparing effects of a low-energy diet and a high-protein low-fat diet on sexual and endothelial function, urinary tract symptoms, and inflammation in obese diabetic men, J Sex Med, 2011;8(10):2868–75.
  45. Snel M, van Diepen JA, Stijnen T, et al., Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetic patients, Food Chem Toxicol, 2011;49(12):3104–11.
  46. Balbo M, Leproult R, Van Cauter E, Impact of sleep and its disturbances on hypothalamo-pituitary-adrenal axis activity, Int J Endocrinol, 2010;2010:759234.
  47. Foley D, Ancoli-Israel S, Britz P, Walsh J, Sleep disturbances and chronic disease in older adults: Results of the 2003 National Sleep Foundation sleep in America survey, J Psychosom Res, 2004;56(5):497–502.
  48. Buysse DJ, Thompson W, Scott J, et al., Daytime symptoms in primary insomnia: A prospective analysis using ecological momentary assessment, Sleep Med, 2007;8(3):198–208.
  49. Chasens ER, Sereika SM, Burke LE, Daytime sleepiness and functional outcomes in older adults with diabetes, Diabetes Educ, 2009;35(3):455–64.
  50. Punjabi NM, Polotsky VY, Disorders of glucose metabolism in sleep apnea, J Appl Physiol, 2005;99(5):1998–2007.
  51. Aronsohn RS, Whitmore H, Van Cauter E, Tasali E, Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes, Am J Respir Crit Care Med, 2010;181(5):507–13.
  52. Trento M, Broglio F, Riganti F, et al., Sleep abnormalities in type 2 diabetes may be associated with glycemic control, Acta Diabetol, 2008;45(4):225–9.
  53. Allen RP, Article reviewed: Sleep apnea and daytime sleepiness and fatigue: Related to visceral obesity, insulin resistance, and hypercytokinemia, Sleep Med, 2000;1(3):249–50.
  54. Mills PJ, Kim JH, Bardwell W, et al., Predictors of fatigue in obstructive sleep apnea, Sleep Breath, 2008;12(4):397–9.
  55. Babu AR, Herdegen J, Fogelfeld L, et al., Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea, Arch Intern Med, 2005;165(4):447–52.
  56. Hassaballa HA, Tulaimat A, Herdegen JJ, Mokhlesi B, The effect of continuous positive airway pressure on glucose control in diabetic patients with severe obstructive sleep apnea, Sleep Breath, 2005;9(4):176–80.
  57. Bardwell WA, Moore P, Ancoli-Israel S, Dimsdale JE, Fatigue in obstructive sleep apnea: Driven by depressive symptoms instead of apnea severity?, Am J Psychiatry, 2003;160(2):350–5.
  58. Hong S, Dimsdale JE, Physical activity and perception of energy and fatigue in obstructive sleep apnea, Med Sci Sports Exerc, 2003;35(7):1088–92.
  59. O'Connor PJ, Puetz TW, Chronic physical activity and feelings of energy and fatigue, Med Sci Sports Exerc, 2005;37(2):299–305.
  60. Puetz TW, Flowers SS, O'Connor PJ, A randomized controlled trial of the effect of aerobic exercise training on feelings of energy and fatigue in sedentary young adults with persistent fatigue, Psychother Psychosom, 2008;77(3):167–74.
  61. McMillan EM, Newhouse IJ, Exercise is an effective treatment modality for reducing cancer-related fatigue and improving physical capacity in cancer patients and survivors: A meta-analysis, Appl Physiol Nutr Metab, 2011;36(6):892–903.
  62. Pedersen BK, Exercise-induced myokines and their role in chronic diseases, Brain Behav Immun, 2011;25(5):811–6.
  63. Petersen AM, Pedersen BK, The role of IL-6 in mediating the anti-inflammatory effects of exercise, J Physiol Pharmacol, 2006;57(Suppl. 10):43–51.
  64. Kadoglou NP, Perrea D, Iliadis F, et al., Exercise reduces resistin and inflammatory cytokines in patients with type 2 diabetes, Diabetes Care, 2007;30(3):719–21.
  65. Dekker MJ, Lee S, Hudson R, et al., An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus, Metabolism, 2007;56(3):332–8.
  66. Balducci S, Zanuso S, Nicolucci A, et al., Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss, Nutrition, Metabolism and Cardiovascular Diseases, 2010;20(8):608–17.
  67. American College of Sports Medicine, 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(12):2282–303.

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