Is the whole not greater than the sum of its parts? The case of sarcopenic obesity

See corresponding article on page 125.

Sarcopenia is defined as the loss of muscle mass and function with aging, which accelerates after the seventh decade of life and is a harbinger for the onset of disability and institutionalization (1). Coinciding with this geriatric syndrome is an emerging obesity epidemic such that a subgroup of individuals who meet all of the criteria for both conditions are classified as having sarcopenic obesity. Thus far, the inability to standardize a clinical-research definition of sarcopenic obesity has prevented this field from moving forward. Relying on mathematically derived thresholds from select referent populations for its classification rather than basing definitions on proximal or distal outcomes creates inherent biases and questionable utility when applying definitions to other cohorts with differing baseline, sociodemographic, and comorbid characteristics. Both the European Working Group for the Study of Sarcopenia in Older Adults (1) and the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project (2) have reached separate conclusions on creating standardized cutoffs that could potentially advance research and clinical interventions. Conflicting evidence exists as to whether reduced muscle mass or strength, with or without obesity, can detrimentally affect functional outcomes. The loss of muscle strength, also termed dynapenia, may be a more important factor in sarcopenia because the rate and magnitude of strength loss typically exceed the loss of muscle mass due to neuromuscular alterations associated with normal aging and reduced physical activity (3). Paradoxically, many individuals with obesity not only have increased fat mass but also increased muscle mass. The debate continues as to whether outcomes of sarcopenia with obesity are multiplicative, or whether obesity in this population may have protective effects.

In this issue of the Journal, Hamer and O’Donovan (4) evaluated the BMI and handgrip strength of 6864 participants from the English Longitudinal Study of Ageing over an 8.1-y period. Sarcopenic obesity was defined as the lowest sex-specific tertile of muscle strength and an accompanying BMI (in kg/m²) ≥30. Adjusted all-cause mortality was no higher in sarcopenic obesity than in sarcopenia alone. A sensitivity analysis that used the FNIH cutoffs suggested no higher mortality risk in either sarcopenia or sarcopenic obesity. An exploratory analysis also evaluated changes in weight and strength over time on mortality. Losing weight, irrespective of changes in strength, was associated with an increased mortality risk. The authors concluded that sarcopenic obesity did not confer any greater risk of death than sarcopenia alone and that weight loss in combination with sarcopenia presented the highest risk of death.

The strength cutoffs used in this study exceed those observed in other studies, which suggests that the participants were relatively healthy and strong. They also tended to be young (mean ± SD age: 66.2 ± 9.5 y), which may have made it difficult to accurately observe the long-term effects of BMI and strength on mortality. The use of combinations of BMI and other measures of central adiposity (i.e., waist-hip ratio or waist circumference) or direct measures of fat mass (i.e., dual-energy X-ray absorptiometry, magnetic resonance, or computer tomography) could provide further insight into the effect of obesity and strength. A major strength of this study is the longitudinal evaluation of loss of handgrip strength over 8 y. However, the classification of a 5% loss of handgrip strength does not appear to be clinically meaningful because individual daily variation can range from 3% to 9% (5).

These findings significantly contribute to the debate as to whether sarcopenic obesity presents a higher risk of morbidity and mortality than sarcopenia alone. Previous epidemiologic studies have shown both higher rates of (6, 7) and no difference in (8–10) mortality risk when muscle mass was used to define sarcopenia. Other studies that used handgrip strength with either abdominal obesity (11) or BMI (12) showed no difference in mortality when combining measures in those aged >70 y.

The implications of the results of the study by Hamer and O’Donovan (4) should not be understated. Although muscle strength may be more important than muscle mass in maintaining function in older adults, the current observations suggest that obesity categorized by using BMI may be less of a critical factor in the aging process. Whether this may be due to its poor sensitivity for accurately diagnosing adiposity is unclear (13). It could likewise be due to biological changes observed during the aging process, inflammatory mediators or cytokine production, changes in fat distribution, and possible physiologic interactions between muscle and adipose tissue (1, 2). These current findings confirm that cutoffs can lead to different outcomes. Identifying minimal detectable changes in handgrip strength that alter physical function, particularly in the context of obesity, can be helpful in both longitudinal and intervention studies.

There is still much more research to be done on the topics of sarcopenia and sarcopenic obesity. First, clinicians and researchers need to come to a consensus about a definition for both sarcopenia and obesity. To do that, they must determine the extent in which to use muscle mass, strength, or both, and to establish a common measurement of adiposity in various populations. The much-anticipated International Classification of Diseases, 10th Revision, code for sarcopenia will increase visibility in the clinical setting, but we first need to move beyond the FNIH’s limitations and perhaps distinctively separate the terms of sarcopenia and dynapenia. By doing so, this will prevent confusion in the literature and allow 2 potential distinct paths of research to mature in this field. Future studies should pool large-scale epidemiologic data related to muscle mass, strength, or both and identify whether the combination with BMI, waist circumference, or body fat affects mortality. Only after descriptive studies are completed can researchers focus on pilot interventions as an intermediary step to focusing on population-based health management that targets sarcopenia and obesity alone, or together, through nutritional and physical activity interventions. This study refutes Aristotle’s common thinking that the whole is greater than the sum of its parts. Although we traditionally think of obesity and sarcopenia to be independently associated with adverse outcomes in older adults, those fulfilling both criteria may not necessarily be incrementally at higher risk of disability, institutionalization, and mortality. We may need to either think twice about how to manage this subgroup population or focus less on obesity in those with sarcopenia.