ESPEN endorsed recommendationMuscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: From sarcopenic obesity to cachexia☆
Introduction
A great achievement of modern medicine is the ability to stabilize chronic diseases, leading to extended life expectancy of populations. The chronically ill patient journey, however, is often associated with metabolic abnormalities and alterations in body composition (i.e., muscle loss with changes in adipose tissue mass) which affect disease outcome and increase health care burden and cost. A physiological decline of skeletal muscle tissue is also an important feature of the aging process. There are strict relationships between muscle loss associated with aging and that due to chronic diseases. In addition, decreased physical activity and muscle unloading are key variables affecting skeletal muscle mass and body composition in aging and chronic disease.
The term sarcopenia was originally introduced to define age-related skeletal muscle decline, however it is now used to indicate any loss of muscle tissue and function due to aging, chronic diseases (including cancer), low protein-energy intake and physical inactivity.1, 2 Other definitions may be used to describe decreases in muscle mass and function. The term wasting describes disease- and cancer-related muscle loss.3 Dynapenia defines decreased contractility and loss of strength.4 Muscle loss secondary to inactivity and unloading is often referred to as disuse atrophy.5 More recently, Fearon et al. proposed the term of “myopenia” to indicate a clinically relevant degree of muscle loss that is also associated with impaired contractile function.6 In 2010 the Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN) defined sarcopenia as any loss of skeletal muscle mass and strength secondary to aging and chronic diseases including cancer.1 Subsequently, it was agreed to continue the common efforts aimed at improving the knowledge about sarcopenia, cachexia, pre-cachexia, sarcopenic obesity in aging and chronic diseases among the scientific community. The process for the production of the present document was started in September 2012 in Barcelona, during the joint meeting of the two ESPEN SIGs. The draft of the paper was elaborated during the first semester of 2013. The manuscript draft was then circulated among the participants to the two SIGs (listed in the acknowledgments section in this paper) and progressively improved and integrated based on the indications of the participants. The endorsement of the document by the two SIGs was obtained in September 2013 in Leipzig, during the annual joint meeting of the 2 SIGs. In agreement with our previous definition,1 in the present paper we will use the term sarcopenia to define any clinically relevant skeletal muscle loss and dysfunction associated with aging, chronic diseases, cancer, low protein-energy intake and physical inactivity. This definition is also in agreement with the European Working Group on Sarcopenia in Older People (EWGSOP) that in 2010 developed a consensus document on sarcopenia endorsed by the following organizations: European Geriatric Medicine Society (EUGMS), the European Society for Clinical Nutrition and Metabolism (ESPEN), the International Association of Gerontology and Geriatrics—European Region (IAGG-ER) and the International Academy of Nutrition and Aging (IANA).2 The EWGSOP made a distinction between aging-associated sarcopenia (primary sarcopenia) and disease-associated sarcopenia (secondary sarcopenia).2 However, it is difficult to distinguish primary from secondary sarcopenia because 90–95% of older adults have at least one chronic disease, and 70–75% have two or more comorbidities.7 Evidence indicates that chronic diseases prevalence is increasing over the last decades.7
In the present joint document elaborated by the ESPEN SIG “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics” we will try to highlight that:
- (a)
criteria for a clinical diagnosis of sarcopenia are required (see: Clinical diagnosis of sarcopenia);
- (b)
sarcopenia is a key feature of age- and disease-related malnutrition (see: Skeletal muscle as a marker of nutritional status);
- (c)
sarcopenia is a multifactorial disorder where specific mechanisms related to aging, chronic disease or inactivity are difficult to distinguish in individual subjects; in addition, sarcopenia includes both muscle loss and muscle dysfunction, the latter not only involves contractile impairment but also metabolic and endocrine abnormalities affecting whole-body metabolism, systemic inflammation and immune system regulation (see: Muscle dysfunction: impaired contractile, metabolic and endocrine functions);
- (d)
sarcopenia is a major determinant of disease outcome and longevity (see: Impact of sarcopenia on outcomes);
- (e)
there are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases leading to the two different paradigms of sarcopenia, i.e., cachexia and sarcopenic obesity (see: Cachexia and sarcopenic obesity); and
- (f)
cost-effective control of chronic disease and optimal aging require sarcopenia prevention, diagnosis and treatment (see: Sarcopenia of aging and chronic diseases: towards a clinical definition and therapy).
Section snippets
Clinical diagnosis of sarcopenia
Currently proposed criteria for sarcopenia assessment in a clinical setting include determination of muscle mass, strength and physical performance (Table 1).2, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Muscle mass can be measured by anthropometry,8 bioimpedance analysis (BIA),2, 9, 13, 15 dual energy X-ray absorptiometry (DXA),11, 12 computed tomography (CT) scan10, 11 and magnetic resonance imaging (MRI). BIA cannot reliably assess skeletal muscle mass in patients with body fluid abnormalities, as
Skeletal muscle as a marker of nutritional status
The role of malnutrition in increasing morbidity and mortality in aging as well as in patients with chronic diseases and cancer has been long recognized.19, 20 The hallmark of disease-related malnutrition is the unintentional loss of body weight secondary to the variable combination of reduced food intake, impaired substrate utilization and increased needs. Indeed, in most observational studies or randomized controlled trials, the assessment of nutritional status was mainly based on changes in
Muscle dysfunction: impaired contractile, metabolic and endocrine functions
Skeletal muscle is the largest organ in the human body accounting for about 40–50% of total weight in physiological conditions. Muscle fiber contraction permits locomotion and other body movements, maintenance of posture, respiration (diaphragm and intercostal muscles) and communication (verbal and facial muscles). Skeletal muscle is also involved in a number of metabolic functions such as energy homeostasis, heat regulation, insulin sensitivity and amino acid metabolism. Skeletal muscle has
Impact of sarcopenia on outcomes
Recent epidemiological evidence suggests that the harmful effect of low BMI on outcomes is largely due to the deleterious effects of muscle loss and dysfunction (Table 4).14, 26, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117 A number of epidemiological evidence indicates muscle depletion as reliable marker of poor prognosis in chronic diseases. Muscle loss is frequently found in end-stage liver disease,118 in these patients sarcopenia increased
Cachexia and sarcopenic obesity
While impaired energy balance mainly affects adipose tissue and fat mass, inflammation, catabolic hormones, inactivity and insufficient protein intake are the main drivers of sarcopenia of aging and chronic diseases (Fig. 5).123 We have recently defined cachexia and pre-cachexia as conditions characterized by actual or potential unintentional weight loss associated with systemic inflammation.1, 124 In these conditions, systemic inflammation is associated with anorexia and low nutrient intake,
Sarcopenia of aging and chronic diseases: towards a clinical definition and therapy
It is becoming increasingly clear that the spectrum of body composition changes in chronic diseases and aging is extremely wide, ranging from the minimal or potential weight loss of pre-cachexia to the extreme loss of fat and muscle in refractory cancer cachexia,11 to the high BMI of sarcopenic obesity. Nonetheless, sarcopenia with muscle loss and dysfunction is a common feature of virtually all chronic diseases characterized by inactivity and systemic inflammation as well as of aging. Reliable
Conclusions
The spectrum of body composition changes in disease states is extremely wide, ranging from the minimal or potential weight loss of pre-cachexia to the extreme loss of fat and muscle in refractory cancer cachexia, to the high BMI of sarcopenic obesity. During the last few years, the progressive understanding of the pathophysiology and clinical impact of disease-related changes in body composition, has highlighted the central role played by skeletal muscle loss in negatively influencing morbidity
Conflict of interest
The Authors declare they have no conflict of interest.
Acknowledgments
We thank all members of the Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN). We acknowledge the contribution of the following SIG members for critical revision of the manuscript: Stefan Anker, Charité, Campus Virchow, Klinikum, Berlin, Germany; Didier Attaix, INRA de Theix, Ceyrat, France; Vickie Baracos, University of Alberta, Edmonton, Alberta, Canada; Juergen
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Joint document endorsed by Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN).
- d
ESPEN-SIG “Cachexia-Anorexia in Chronic Wasting Diseases”.
- e
ESPEN-SIG “Nutrition in Geriatrics”.
- f
These authors equally contributed to conception and writing of the paper.