Sarcopenic obesity

Sarcopenic obesity is a combination of two disease states, sarcopenia and obesity. Sarcopenia is the muscle mass/strength/physical function loss associated with increased age,^[1] and obesity is based off a weight to height ratio or body mass index (BMI) that is characterized by high body fat or being overweight.^[2]

The risk of sarcopenic obesity increases with age, and its consequences are a health concern in an ageing population.^[3] This condition accelerates muscle mass and function loss as mentioned above, and is a particular concern for the elderly due to its compounding effects on mobility and overall health.

An increased subset of adults over the age of 65 have been classified as having sarcopenic obesity. There is an association between the loss in muscle mass/strength/physical function of sarcopenia and high body fat in obesity as the increased inactivity (sedentary lifestyle) that can occur with a loss in physical function and aging can lead to increase in weight as body fat increases.^[4]

In regard to sarcopenic obesity prevalence, there are shortcomings in statistical evidence as there are inconsistent definitions of both obesity and sarcopenia across mathematical/muscle mass definitions. Therefore, there is a critical need for a consensus definition for sarcopenic obesity and thus its clinical importance.^[1] Additionally, limited data among different populations means that future retrospective research studies could clarify statistical data and provide more robust evidence. However, this does not preclude a relationship between the two conditions or dismiss the possibility of associated symptoms and or health complications.

These two disease states are synergistic or linked together, as the increase in progression of one disease state increases the severity of the other and vice versa. A Pearson Chi-Square test performed on a sample size of 1637 patients from 2019-2021 in community/outpatient clinics at Prince of Wales Hospital determined that Obesity is a risk factor of sarcopenia when obesity is defined as BF% compared to BMI.^[5] This can be attributed to high amounts of lean tissue or high muscle mass even though the clinical BMI can be diagnosed as obesity.

Pathogenesis

The pathogenesis of sarcopenic obesity involves multiple factors, including aging, lack of physical activity, malnutrition/vitamin imbalances, insulin resistance, and hormonal changes -> body composition changes. The exact pathophysiology is not well understood, however these factors have been studied in the production of sarcopenic obesity. These factors increase ectopic/omental fat deposition, insulin resistance, while decreasing metabolic rate, physical activity, and anabolic hormones.^[6]

It is thought that GDF15 and FGF21 (protein/cytokine that is biomarker for cell injury/inflammation in response to stress) are increased in sarcopenic obesity. Myostatin is also increased. In the fat, lipotoxicity and chronic inflammation are increased in addition to accumulation of immune cells. In the muscle, mitochondrial dysfunction, oxidative stress (imbalance of free radicals and antioxidants that leads to cell damage), myosteaosis (fat accumulation in skeletal muscles), and anabolic resistance (reduced stimulation of muscle to amount of protein) can occur.^[6]

Overall, the cycle of adipose and muscle tissues lead to expansion of white adipose tissue into muscle tissue. This inhibits protein synthesis, resulting in decline of muscle mass and promotes other mechanisms e.g. insulin resistance. The release of cytokines as well inhibits insulin production, and other mechanisms that increase risk of disease e.g Cardiovascular issues that increase risk of death and decreased life span.

Symptoms

The symptoms are similar to those of sarcopenia and obesity. The individual may show a body mass index that is appropriate and healthy to his or her age but will look fat in appearance.

People who have sarcopenia are experiencing gradual loss of muscle. This condition commonly presents as reduced endurance, reduced speed while walking, imbalance with increased risk of falls, struggles with everyday activity, difficulty climbing stairs, and loss of muscle size. ^[6]

Sarcopenic obesity also involves obesity. People living with obesity experience an array of symptoms, including difficulty breathing, joint and back pain, a limited ability to participate in physical tasks, snoring, frequently experiencing fatigue, and excessive perspiration. In some patients, a range of comorbidities can coincide with sarcopenic obesity, for example cardoivascular disease, dementia, fractures, diabetes, and even some cancers. In some cases, if a person already has pre-existing conditions, they can worsen if they develop sarcopenic obesity.^[7] The effects of obesity are not only physical, people can also have some mental effects. Some of these include, low confidence which can present as doubting ones ability, worry, uncertainty, and being hesitant while assigned or performing tasks. People with obesity also tend to have low self-esteem. ^[8]

Causes

Sarcopenic obesity primarily stems from changes in body composition due to an increase in age, hormonal changes, lack of exercise and a healthy diet, and other diseases.

Aging

Aging is the main factor that leads to a change in body composition. These are mainly decreases in muscle strength, increases in total fat mass, and decreases in peripheral subcutaneous fat,^[9] all of which can also be attributed to a decline in exercise and reduced basal metabolic rate. Hormonal changes also occur as a person ages, resulting in further changes in muscle composition. ^[1]

Hormonal Changes

Insulin resistance often increases as a person ages and is commonly linked with obesity. Obesity is often characterized as extreme adipose tissue growth due to a decrease in energy expenditure as well as an increase in nutrition. Obesity can also lead to inflammation, which plays an additional factor in causing insulin resistance. ^[10] Insulin plays a powerful role in protein synthesis since it increases intracellular uptake of short-chain amino acids and regulates expression of albumin and myosin. Insulin's regulation of hepatic and muscle cell enzymes also helps control protein degradation. ^[11] Thus, insulin resistance can lead to an increase in protein breakdown and a decrease in protein synthesis in skeletal muscle. ^[12]

Obesity can also lead to lower levels of testosterone, insulin-like growth factor 1 (IGF-1), and other anabolic hormones. The high amount of circulating free fatty acids also inhibits growth hormone production. These hormonal changes are often associated with a loss in muscle strength and mass.^[1]

Inflammation

Inflammation is one of the key factors that contributes to the reduction of muscle mass and strength among sarcopenic obesity. Adipose tissue secretes hormones and proteins, such as pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) and adipokines (lectin and adiponectin).

Because there is a larger number of adipose tissue in those that are obese, the inflammatory response is up-regulated.^[1] This inflammation can induce insulin resistance, leading to a decrease in skeletal muscle strength and mass. Inflammation can also directly cause muscle atrophy by suppressing protein synthesis and inducing the breakdown of proteins. It indirectly affects muscle mass by causing metabolic disorders in the digestive system, liver, and other cells.^[13]

Exercise

One of the factors that cause sarcopenic obesity is a decline in physical activity, often as a result of aging. This decrease in exercise leads a decrease in muscle mass and strength. This leads to a decrease in basal metabolic rate, allowing for a greater accumulation of fat. ^[14] As the body continues to age, the lack of physical activity, as well as other factors, further prevents a person from continuously exercising. In addition, a lack of exercise can lead to decreases in muscle protein synthesis and affect hormonal balances.^[1]

Diagnosis

Sarcopenic obesity is a combination of high body fat and low body mass index. Can be diagnosed by measures such as waist-hip ratio.

Sarcopenic obesity is defined as the presence of increased levels of adipose tissue and a below average muscle mass and function in a patient. Diagnostic procedure for sarcopenic obesity involves a number of body composition assessments a person has to undergo.^[15] Sarcopenic obesity is slightly more challenging to diagnose compared to other disease and it tends to be under diagnosed in all populations. This is a condition that is thought to affect the older population since as people age, they tend to loose muscle mass. Older people are also less likely to engage in physical activity and this can lead to an increase in weight. The intricate definition of sarcopenic obesity is thought to cause people to be under-diagnosed especially in the younger population. Some research points to anthropometric diagnosis based on south Asian cut offs to be the most efficacious way to diagnose sarcopenic obesity. ^[16] Anthropometric measurements is defined as human measurements. Diagnosing using this method involves a non-intrusive assessable measurements of the body. The measurements include height, weight, body mass index (BMI), head circumferences, skinfold thickness, and body circumferences to asses fat this is compromised of waist, hip and limbs. Normal values are set by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO) based on a nutritional status evaluation and people with abnormal values undergo further evaluation. ^[17] Abnormal values for obesity is a BMI greater than 30 kg/m^2 or by fat levels and also modified body composition caused by low skeletal muscle operation and mass.^[18]

Treatment

As of now, there are no therapies that directly cure sarcopenic obesity. However, there are a few strategies, including lifestyle modifications and pharmacological, that can manage both disease states. An appropriate weight training and weight loss program can help to improve the patient's condition.

Weight Loss + Exercise

Through caloric restriction of at least 10%, weight loss is feasible. Though, through weight loss by diet changes, this may cause the loss of muscle mass and body mass index which exacerbates the effects of sarcopenia.^[19] Regular exercise, along with diet changes has shown to reduce muscle mass loss and increase muscle strength. Incorporating progressive resistance training may counteract sarcopenia by causing muscle hypertrophy and encouraging muscle protein synthesis. Elastic resistance training incorporated into exercise also has shown to reduce muscle mass loss while losing weight.^[20] This is important for patients to implement into their routine in order to both lose weight without losing muscle mass.^[21] In patients that combined both effective weight loss and exercise, muscle strength increased while body mass decreased, indicating that there was an increase in muscle mass. This method is known to be the most effective treatment for sarcopenic obesity.

Nutrition

As individuals age, their body composition, amount of physical activity, and diet contribute to their decrease in muscle mass. Protein, on the other hand, is a necessary macronutrient for building muscle. Although protein is an important component to a balanced meal, older patients start to lose the ability to synthesize muscle through protein and amino acid consumption, and even if elderly patients increase their protein intake, studies show that muscle mass synthesis does not increase compared to young patients. Instead, elderly patients should focus on consuming high quality protein containing leucine, an amino acid. ^[22] Since sarcopenic obesity is mostly prevalent in elderly patients, it is important to consume the appropriate amount of protein to prevent muscle mass loss. Magnesium, selenium, and vitamin D supplementation may also aid in muscle mass.

Myostatin Inhibitors

Myostatin is a protein found on muscle cells that inhibit the growth of muscles. Elderly patients are known to have higher levels of myostatin compared to younger patients, thus this protein poses a risk of developing sarcopenia. By inhibiting this protein, it may help reduce the process of muscle breakdown.^[23] Elderly mice that were administered myostatin inhibitors showed to have lower levels of fat and denser muscles compared to mice that did not take myostatin inhibitors. They suggest that reducing levels of myostatin in the elderly may lessen the chance of heart disease, diabetes, and sarcopenia. Although most data seems promising for animals, there is limited and ongoing research on humans.^[24]

Testosterone

Testosterone levels are much lower in elderly individuals compared to younger individuals, and lower than normal testosterone levels in males are linked to pathologies such as cardiovascular risks, obesity, and sarcopenia.^[25] One study illustrated that both younger and older males on testosterone therapy showed improvement on muscle mass via testosterone enanthate injections,^[26] and another study described decreased fat mass in older males over the age of 65 via testosterone patches.^[27] This type of treatment is dependent on serum testosterone levels of male patients, and is not the sole type of treatment for sarcopenic obesity.

Complications/Conclusions

Low muscle mass or obesity are risk factors for reduced physical capacity and quality of life.

As a result of sarcopenic obesity, the risk of cardiovascular disease, cancer, type 2 diabetes, fractures, disability, and quality of life as above is affected. This is important because it is associated with all-cause mortality. In the event of early diagnosis, preventative treatment to delay the degradation of muscle and weight/fat management could prove to be beneficial.^[28]

Preventatively, a diet high in protein combined with physical activity outdoors can reduce the risk of sarcopenic obesity. With the controllable risk factors being lack of physical activity and malnutrition/vitamin imbalances, mitigating these can improve outcomes. Physical activity and proper nutritional supplementation is one of the important non-pharmacological options to delay and/or treat sarcopenic obesity, but it does come with limitations. If the individual cannot engage in physical activity, or is limited in walking capacity or higher intensity exercise can be a limitation to muscle growth beyond the age. Alternatively, if the individual does not have high amounts of muscle mass to begin with building muscle at a later age can prove to be challenging due to sarcopenia.^[28]

References

^ ^a ^b ^c ^d ^e ^f Batsis, John A.; Villareal, Dennis T. (September 2018). "Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies". Nature Reviews. Endocrinology. 14 (9): 513–537. doi:10.1038/s41574-018-0062-9. ISSN 1759-5029. PMC 6241236. PMID 30065268. Cite error: The named reference ":0" was defined multiple times with different content (see the help page).
^ Apovian, Caroline M. (2016-06-02). "Obesity: Definition, Comorbidities, Causes, and Burden". Impact of Obesity Interventions on Managed Care. 22. {{cite journal}}: Cite journal requires |journal= (help)
^ Bilski, Jan; Pierzchalski, Piotr; Szczepanik, Marian; Bonior, Joanna; Zoladz, Jerzy A. (2022-01-04). "Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines". Cells. 11 (1): 160. doi:10.3390/cells11010160. ISSN 2073-4409. PMC 8750433. PMID 35011721.
^ Donini, Lorenzo M.; Busetto, Luca; Bischoff, Stephan C.; Cederholm, Tommy; Ballesteros-Pomar, Maria D.; Batsis, John A.; Bauer, Juergen M.; Boirie, Yves; Cruz-Jentoft, Alfonso J.; Dicker, Dror; Frara, Stefano; Frühbeck, Gema; Genton, Laurence; Gepner, Yftach; Giustina, Andrea (2022-02-23). "Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement". Obesity Facts. 15 (3): 321–335. doi:10.1159/000521241. ISSN 1662-4025. PMC 9210010. PMID 35196654.
^ Liu, Chaoran; Cheng, Keith Yu-Kin; Tong, Xin; Cheung, Wing-Hoi; Chow, Simon Kwoon-Ho; Law, Sheung Wai; Wong, Ronald Man Yeung (2023-03-01). "The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity". Frontiers in Endocrinology. 14: 1077255. doi:10.3389/fendo.2023.1077255. ISSN 1664-2392. PMC 10016224. PMID 36936175.
^ ^a ^b ^c Ardeljan, Andrew D.; Hurezeanu, Razvan (2024), "Sarcopenia", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32809648, retrieved 2024-07-23
^ Wei, Shibo; Nguyen, Thanh T.; Zhang, Yan; Ryu, Dongryeol; Gariani, Karim (2023). "Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management". Frontiers in Endocrinology. 14: 1185221. doi:10.3389/fendo.2023.1185221. ISSN 1664-2392. PMID 37455897.
^ "Obesity". nhs.uk. 2017-11-23. Retrieved 2024-07-25.
^ Ji T, Li Y, Ma L (April 2022). "Sarcopenic Obesity: An Emerging Public Health Problem". Aging and Disease. 13 (2): 379–388. doi:10.14336/AD.2021.1006. PMC 8947824. PMID 35371597.
^ Wondmkun, Yohannes Tsegyie (2020-10-09). "Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13: 3611–3616. doi:10.2147/DMSO.S275898. ISSN 1178-7007. PMC 7553667. PMID 33116712.
^ Vargas, Elizabeth; Joy, Neena V.; Carrillo Sepulveda, Maria Alicia (2024), "Biochemistry, Insulin Metabolic Effects", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30252239, retrieved 2024-07-25
^ Liu, Zi-jian; Zhu, Cui-feng (2023-03-15). "Causal relationship between insulin resistance and sarcopenia". Diabetology & Metabolic Syndrome. 15 (1): 46. doi:10.1186/s13098-023-01022-z. ISSN 1758-5996. PMC 10015682. PMID 36918975.
^ Ji, Yanan; Li, Ming; Chang, Mengyuan; Liu, Ruiqi; Qiu, Jiayi; Wang, Kexin; Deng, Chunyan; Shen, Yuntian; Zhu, Jianwei; Wang, Wei; Xu, Lingchi; Sun, Hualin (2022-08-29). "Inflammation: Roles in Skeletal Muscle Atrophy". Antioxidants. 11 (9): 1686. doi:10.3390/antiox11091686. ISSN 2076-3921. PMC 9495679. PMID 36139760.
^ Kim, Yoon Jung; Moon, Shinje; Yu, Jae Myung; Chung, Hye Soo (September 2022). "Implication of diet and exercise on the management of age-related sarcopenic obesity in Asians". Geriatrics & Gerontology International. 22 (9): 695–704. doi:10.1111/ggi.14442. ISSN 1444-1586. PMC 9544230. PMID 35871525.
^ Donini, Lorenzo M.; Busetto, Luca; Bischoff, Stephan C.; Cederholm, Tommy; Ballesteros-Pomar, Maria D.; Batsis, John A.; Bauer, Juergen M.; Boirie, Yves; Cruz-Jentoft, Alfonso J.; Dicker, Dror; Frara, Stefano; Frühbeck, Gema; Genton, Laurence; Gepner, Yftach; Giustina, Andrea (2022). "Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement". Obesity Facts. 15 (3): 321–335. doi:10.1159/000521241. ISSN 1662-4033. PMC 9210010. PMID 35196654.
^ Kalra, Sanjay; Agrawal, Navneet; Kapoor, Nitin (November 2022). "Sarcopenic Obesity: Anthropometric Diagnosis". JPMA. The Journal of the Pakistan Medical Association. 72 (11): 2337–2338. doi:10.47391/JPMA.22-110 (inactive 2024-07-30). ISSN 0030-9982. PMID 37013320.{{cite journal}}: CS1 maint: DOI inactive as of July 2024 (link)
^ Casadei, Kyle; Kiel, John (2024), "Anthropometric Measurement", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30726000, retrieved 2024-07-30
^ "Sarcopenic Obesity - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-07-30.
^ Waters DL, Ward AL, Villareal DT (October 2013). "Weight loss in obese adults 65years and older: a review of the controversy". Experimental Gerontology. 48 (10): 1054–1061. doi:10.1016/j.exger.2013.02.005. PMC 3714333. PMID 23403042.
^ Liao, Chun-De; Tsauo, Jau-Yih; Huang, Shih-Wei; Ku, Jan-Wen; Hsiao, Dun-Jen; Liou, Tsan-Hon (2018-02-02). "Effects of elastic band exercise on lean mass and physical capacity in older women with sarcopenic obesity: A randomized controlled trial". Scientific Reports. 8 (1): 2317. Bibcode:2018NatSR...8.2317L. doi:10.1038/s41598-018-20677-7. ISSN 2045-2322. PMC 5797161. PMID 29396436.
^ Frimel TN, Sinacore DR, Villareal DT (July 2008). "Exercise attenuates the weight-loss-induced reduction in muscle mass in frail obese older adults". Medicine and Science in Sports and Exercise. 40 (7): 1213–1219. doi:10.1249/MSS.0b013e31816a85ce. PMC 2650077. PMID 18580399.
^ Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Zhang, Xiao-Jun; Volpi, Elena; Wolf, Steven E.; Aarsland, Asle; Ferrando, Arny A.; Wolfe, Robert R. (March 2004). "Amino acid ingestion improves muscle protein synthesis in the young and elderly". American Journal of Physiology. Endocrinology and Metabolism. 286 (3): E321–328. doi:10.1152/ajpendo.00368.2003. ISSN 0193-1849. PMID 14583440.
^ Schirwis, E.; Agbulut, O.; Vadrot, Nathalie; Mouisel, E.; Hourdé, C.; Bonnieu, A.; Butler-Browne, G.; Amthor, H.; Ferry, A. (February 2013). "The beneficial effect of myostatin deficiency on maximal muscle force and power is attenuated with age". Experimental Gerontology. 48 (2): 183–190. doi:10.1016/j.exger.2012.11.008. ISSN 1873-6815. PMID 23201547.
^ Jackson, Melissa F.; Luong, Dung; Vang, Dor Dor; Garikipati, Dilip K.; Stanton, James B.; Nelson, O. Lynne; Rodgers, Buel D. (June 2012). "The aging myostatin null phenotype: reduced adiposity, cardiac hypertrophy, enhanced cardiac stress response, and sexual dimorphism". The Journal of Endocrinology. 213 (3): 263–275. doi:10.1530/JOE-11-0455. ISSN 1479-6805. PMID 22431133.
^ Buvat, Jacques; Maggi, Mario; Guay, André; Torres, Luiz Otavio (January 2013). "Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment". The Journal of Sexual Medicine. 10 (1): 245–284. doi:10.1111/j.1743-6109.2012.02783.x. ISSN 1743-6109. PMID 22971200.
^ Bhasin, Shalender; Woodhouse, Linda; Casaburi, Richard; Singh, Atam B.; Mac, Ricky Phong; Lee, Martin; Yarasheski, Kevin E.; Sinha-Hikim, Indrani; Dzekov, Connie; Dzekov, Jeanne; Magliano, Lynne; Storer, Thomas W. (February 2005). "Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle". The Journal of Clinical Endocrinology and Metabolism. 90 (2): 678–688. doi:10.1210/jc.2004-1184. ISSN 0021-972X. PMID 15562020.
^ Snyder, P. J.; Peachey, H.; Hannoush, P.; Berlin, J. A.; Loh, L.; Lenrow, D. A.; Holmes, J. H.; Dlewati, A.; Santanna, J.; Rosen, C. J.; Strom, B. L. (August 1999). "Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age". The Journal of Clinical Endocrinology and Metabolism. 84 (8): 2647–2653. doi:10.1210/jcem.84.8.5885. ISSN 0021-972X. PMID 10443654.
^ ^a ^b Wang, Mina; Tan, Yan; Shi, Yifan; Wang, Xu; Liao, Zehuan; Wei, Peng (2020-08-25). "Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments". Frontiers in Endocrinology. 11: 568. doi:10.3389/fendo.2020.00568. ISSN 1664-2392. PMC 7477770. PMID 32982969.