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Diabetes Management Fatigue in Adults with Type 2 Diabetes – An Overview of Current Understanding and Management Approaches Cynthia Fritschi 1 and Anne M Fink 2 1. Assistant Professor; 2. Research Associate, Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing, Chicago, Illinois, US Abstract 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 pharmacological and behavioural therapies. Keywords Type 2 diabetes, fatigue, inflammation, patient-reported outcomes, symptoms, management Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors thank Kevin Grandfield, Publication Manager for the University of Illinois at Chicago Department of Biobehavioral Health Science, for editorial assistance. Received: 19 July 2012 Accepted: 3 September 2012 Citation: European Endocrinology, 2012;8(2):80–3 Correspondence: Cynthia Fritschi, University of Illinois at Chicago College of Nursing (MC 802), 845 South Damen Avenue, Chicago, IL 60612, US. E: Fritschi@uic.edu 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 standardised 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 may be is associated with higher body mass index (BMI), 1,7,12 the presence of co-morbid 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 glycaemic 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 levels 10,11,19,20 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 80 discussion of fatigue interventions will focus on the few available pharmacological and behavioural interventions in patients with type 2 diabetes to impact inflammation and fatigue. Pharmacological Therapy Pharmacological fatigue therapies are in their infancy. The primary therapeutic target has been reducing symptoms of fatigue, depression, and pain associated with high levels of pro-inflammatory cytokines. Disease-modifying antirheumatic drugs, including etanercept, a TNF-α receptor fusion protein, have been shown to decrease fatigue and improve physical and psychological function in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis. 25–28 To date, there are few data regarding pharmacological therapies for inflammation and fatigue in type 2 diabetes. Recent findings from a placebo-controlled, double-blind study of IL-1β antagonism with a monoclonal anti-IL-1β antibody in 30 patients with type 2 diabetes indicated a dose-dependent decrease in fatigue. 3 Anti-inflammatory agents therefore show promise, but further long-term studies are imperative for evaluating the effectiveness and potential for adverse effects. Such agents may place patients with type 2 diabetes at higher risk for infection, and the long-term benefits are unknown. In the place of available pharmacological agents, several behavioural therapies were been associated with reductions in fatigue levels and we discuss these below. Weight Reduction and Dietary Changes Fatigue was strongly associated with increased BMI and obesity in both the general population 29–31 and patients with type 2 diabetes. 7,32,33 © TOUCH MEDICAL MEDIA 2012