In this mini-review pathophysiology, comorbidities, diagnosis and management of sarcopenic obesity (SO) are discussed. SO is a high risk geriatric syndrome more associated with osteoarthritis (OA), falls, dementia and increased cardiometabolic risk profiles than obesity alone. Decreased physical activity, low-grade chronic inflammation, oxidative stress and insulin resistance all of which being by-products of obesity and the aging process are involved. Easy diagnostic tools are not yet available and sophisticated DXA and SPECT scans are not always feasible. Prevention and resistance exercise programs combined with protein supplementation are the cornerstone of SO management. When male SO patients can be easily identified, treatment with selective androgen receptor modulators (SARMs) might be considered in the near future.
The prevalence of obesity in combination with sarcopenia, the age-related loss of muscle mass and strength or physical function, is increasing in adults aged 65 and older. A major subset of adults over the age 65 is now classified as having sarcopenic obesity, a high risk geriatric syndrome. Moreover, recent estimates suggest that 37% of U.S. adults aged 65 year and older are obese . The specific criteria for defining sarcopenic obesity (SO) are somewhat arbitrary and depend on the study cited . Thus, the prevalence of SO varies from 4% to 84% in men and from 4% to 94% in women . Older adults with SO have higher risks of mobility disability, cardiometabolic disease and mortality . In this mini-review pathophysiology, comorbidities, diagnosis and management of SO are discussed.
Human aging is associated with a progressive decline of skeletal muscle mass. Several studies have suggested that muscle mass decreases by approximately 6% per decade after midlife . Lower muscle mass results in decreased muscle strength . There are significant differences among individuals in peak muscle mass, the age at which muscle loss starts, and the amount of muscle that is lost over time . At the cellular level sarcopenia is accompanied by a loss of innervation and adaptive changes in the proportion of slow and fast motor units, as well as in the cross-sectional area of muscle fibers . Several mechanisms have been linked to the development of sarcopenia . Most mechanisms are also associated with visceral obesity, leading to a vicious circle of interacting risk factors. Insulin resistance plays an important role in obesity and results in muscle fiber atrophy and mitochondrial dysfunction [9,10]. Age-related changes in hormones play a pivotal role and affect the anabolic and catabolic processes in skeletal muscle [11,12]. Reduced androgen and estrogen levels decrease muscle mass and strength . In addition, sarcopenia is an inflammatory state that is driven by proinflammatory cytokines and oxidative stress . Oxidative stress modulates the expression of transcription factors, such as nuclear factor-kappa B (NF-kB), which enhances proteolytic pathways and increases the production of proinflammatory cytokines . Tumor necrosis factor-alpha (TNF-alpha) impairs protein synthesis in skeletal muscle by altering translation initiation, which may contribute to sarcopenia . Higher levels of interleukin-6 (IL-6) and C-reactive protein (CRP) are associated with a greater decline in muscle strength . Myostatin (growth differentiation factor 8) inhibits muscle cell growth and differentiation and could be a potential mediator of sarcopenia .
Excess nutrient availability and tissue delivery, particularly saturated fat and glucose further contribute to the cluster of insulin resistance, inflammation and oxidative stress that occur in obesity. Resulting adipose tissue dysfunction develops in response to the enhanced demand for lipid storage [18-20]. These changes may result in an “anabolic resistance state” to nutrients where the muscle protein synthesis from nutrients is blunted [21-24]. Mtochondrial changes are observed in obese skeletal muscle until late stages [25,26]. Their onset may however exacerbate oxidative stress and related metabolic cascades leading to insulin resistance and catabolism. Potential reduction in ATP production may also result in low muscle strength and endurance capacity [25,26]. Stem cell dysfunction leads to functionally altered muscle stem cells that may undergo adipocyte differentiation and accompanied fat accumulation [27-29]. Low physical contributes to a positive energy balance . Progressive reduction of physical activity is further observed with disease progression due to worsening obesity and musculoskeletal disorders with direct
negative impact on muscle protein turnover and muscle oxidative
and performance capacity [30,31].
Individuals with osteoarthritis (OA) may exhibit a higher
prevalence of SO compared with rheumatoid arthritis (RA)-
. Misra et al. studied a large cohort from the Multicenter
Osteoarthritis (MOST) Study, a longitudinal cohort of individuals
with or at risk for knee OA. Based on body composition from
whole body Dual Energy X-Ray (DXA) subjects were categorized
as obese, sarcopenic obese (SO), sarcopenic and non-sarcopenic
Among 1633 subjects with radiographic knee OA at baseline,
significant increased risk of incident radiographic knee OA was
found among obese (women RR 2,29;95%CI 1,64-3,20;men RR
1,73;95% CI 1,08-2,78) and SO women (RR 1,91;95%CI 1,73-
3,11) but not men ( RR 1,74;95% CI 0,68-4,46) .Sarcopenia was
not associated with knee OA risk (women RR 0,96;95% CI 0,34-
1,30). It was concluded that in this large cohort population,
body composition based obesity and SO but not sarcopenia was
associated with knee OA risk. Weight loss strategies for knee OA
should focus on obesity and SO .
Sarcopenia obesity (SO) results in more physical disability
than sarcopenia alone or obesity alone and has been strongly
implicated in both risk of OA and frailty [34-36]. Total joint
arthroplasty (TJA) in adults with obesity is associated with
increased surgical risk and prolonged recovery. SO is associated
with higher infection rates, poorer function and slower recovery
in other clinical populations, but not thoroughly investigated in
Ma et al. analyzed a cohort of the Framingham Heart
Study’s Offspring and Omni 1 cohorts for mid-adulthood
cardiometabolic risk profiles in patients with SO . Utilizing
BMI and sex-specific 24h urinary creatinine excretion,1019
participants from the Framingham cohorts were categorized
as non-sarcopenia non obese (NSNO); non-obese sarcopenia,
non-SO and SO. Cardiometabolic risk factors were quantified
by standard laboratory assessment cross-sectionally and 10,20
and 30 years before SO assessment. NSNO, sarcopenia, obesity
and SO accounted for 30,0%,39,6%,20,0% and 10,4% of study
participants, respectively. Cross-sectionally, participants with SO
had a higher proportion of hypertension, metabolic syndrome
and type 2 diabetes than those with NSNO or sarcopenia (all
p<0,03) Similar patterns were observed retrospectively at
10,20 and 30 years. Compared with NSNO or sarcopenia SO was
associated with a higher prevalence of type 2 diabetes at 10 years
and hypertension and metabolic syndrome at all three points
before baseline (all p<0,03). Individuals with SO had more type
2 diabetes than those with obesity alone at baseline and 10 years
prior (all p<0,001). The authors conclude that adults with SO had
more adverse midlife cardiometabolic risks, particularly diabetes
10 years earlier.
Pasco et al. examined the association between falls and SO,
among elderly individuals in the population . Participants
were 353 men and 245 women, aged 65-98 years of the Geelong
Osteoporosis Study. Body fat and lean body mass were measured
using dual energy X-ray absorptiometry (DXA). Body fat mass
was expressed as a percentage of weight (%BF) and appendicular
lean mass was adjusted for height (rALM, kg/m2). Poor physical
performance was assessed using the timed up & go (TUG) test.
Sarcopenic obesity referred to low-rALM (T score<1), poor physical
performance (TUG> 10s) and obesity (%BF>25% for men,35%
for women) Fallers were identified by self-report as having had at
least one fall in the previous 12 months. Associations between SO
and falls were determined using logistic regression after adjusting
for age and sex. In total 219 (36,6%) had lower rALM,205(34,2%)
had poor physical performance,466 (77,9%) were obese and
69(11,5%) had SO. There were 170 (28,4%) fallers. Falls were
more common for those with OS than without (28(40,6%) vs
42(26,8%) ;p=0,017). The like li hoof of falls in association with
SO were: SO,OR=1,65 (95%CI 0,96-2,85), sarcopenia, OR=1,52
(0,93-2,47),poor physical performance and obesity, OR=1,74
(1,16-2,61),low r-ALM,OR=1,41 (0,96-2,06),poor physical
performance, OR=1,88 (1,26-2,80),obesity OR=0,88 (0,57-1,35).
The authors conclude that while obesity per se was not associated
with falls there was an increased risk of falls in SO individuals that
was of borderline statistical significance and appeared largely a
consequence of poor physical performance .
Sarcopenia and obesity both negatively impact health
including cognitive function. Their coexcistense however, can pose
an even higher threat likely surpassing their individual effects.
Tolea et al assessed the relationship of SO with performance on
global-and subdomain-specific tests of cognition . The study
was a cross-sectional analysis of data from a series of communitybased
aging and memory studies (n=353) with an average age of
69 years with a clinical visit, valid cognitive (Montreal Cognition
Assessment) test, functional (grip strength, chair stands) and body
composition measurements . The authors found consistent
evidence to link SO to poor global cognitive performance in
community-dwelling older adults. This effect is best captured by
its sarcopenia component with obesity likely having an additive
effect. Several mechanisms may explain the obesity-cognitive
dysfunction link including decreased participation in physical
activity, low-grade chronic inflammation, oxidative stress and
insulin resistance all of which being by-products of the aging
process . The authors conclude that sarcopenia alone and in
combination with SO can be used in clinical practice as indicators
of probable cognitive impairment. At risk older adults may
benefit from programs addressing loss of cognitive function by
maintaining and improving strength and preventing obesity .
The current definitions of SO combine sarcopenia as defined
through variable criteria in the presence of obesity as defined
as BMI>30kg/m2. Simple anthropometric measurements in
obese individuals may be biased by confounding adipose depots.
Radiological methods that include nuclear magnetic resonance
spectroscopy CT scans (SPECT) or dual X-ray absorptiometry have
been considered most accurate but are not always available and
feasible in this older population. Bio-electrical impedance analysis
has been mentioned as an acceptable compromise. Functional
measures are heterogenous and include hand-grip, knee-extensor
strength and various moblity measurements involving postural
and walking tests [42-44]. At this moment there is obviously no
ideal methodology to achieve simultaneously maximal precision,
safety, and routine applicability.
Management strategies for obesity commonly favor diet
changes and aerobic ecercise in order to reduce levels of body fat.
However, this approach doesn’t address the loss of muscle mass
that may occur during weight loss and contribute to sarcopenia.
It is of critical importance that management strategies focus on
maintenance or accretion of muscle mass as well as fat loss in order
to maintain strength, function and resting metabolic rate (RMR).
Resistance exercise in combination with protein supplementation,
prescribed by a dietician, can achieve these goals. In this way an 8
week resistance exercise program with protein supplementation
can improve muscle mass significantly in even frail old men and
women . Any person starting a resistant exercise program
should have at least a dietary protein intake of 1.5 g/kg. This is
nearly twice the recommended daily amount (RDA) of 0,8 g/kg
per day by the Food and Nutrition Board of the U.S. When male SO
patients can be identified routinely in an easy manner, treatment
with selective androgen receptor modulators (SARMs) might be
considered in the near future .
Sarcopenic obesity (SO) is definitely a high risk geriatric
syndrome. Decreased physical activity, low grade chronic
inflammation, oxidative stress and insulin resistance all of which
being by-products of obesity and the aging process are involved
. It is obvious SO is more associated with osteoarthritis (OA),
falls, dementia and increased cardiometabolic risk profiles than
obesity alone. Prevention, resistance exercise programs combined
with dietary protein supplementation are the cornerstone of SO
management . Ideal easy routine diagnostic tools are not
yet available. Radiological techniques measuring total body
composition are most accurate but not always present or feasible
in the elderly. When male SO patients can be easily identified,
treatment with selective androgen receptor modulators (SARMs)
might be considered in the near future .