The Importance of Muscle Versus Fat Mass in Sarcopenic Obesity: A Re-evaluation Using D3-Creatine Muscle Mass Versus DXA Lean Mass Measurements

Abstract Background The combination of sarcopenia and obesity has been associated with physical impairment in older people. However, previous research has relied on assessments of lean mass as a surrogate for muscle mass. We postulate that inaccurate measures of muscle mass may have obscured the role of obesity in sarcopenia and related outcomes. Our aim was to clarify the interactions of muscle and fat with physical performance and adverse outcomes using an accurate measure of muscle mass. Methods In a longitudinal study of >1,300 older men (mean age 84 years), we compared a direct measurement of muscle mass (D3 creatine dilution; D3Cr) with an approximation of muscle mass (appendicular lean mass [ALM] by dual-energy x-ray absorptiometry [DXA]) and their associations with measures of physical performance (gait speed, chair stand time) and adverse outcomes (incident injurious falls and mobility problems). We measured percent fat mass by DXA. Results Low D3Cr muscle mass was strongly associated with decreased performance and increased risk of adverse outcomes. Increased fat mass had little association after accounting for D3Cr muscle mass. In contrast, DXA ALM was minimally associated with performance or adverse outcomes, and fatness remained associated with both outcomes after accounting for DXA ALM. Conclusions When an accurate assessment of muscle mass (rather than lean mass) is used, reduced muscle mass is highly associated with important outcomes and the negative effects of adiposity are minimal, suggesting that obesity has little relevance for the understanding of important adverse health outcomes of sarcopenia in older men.

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THE ASSOCIATION BETWEEN D3CR MUSCLE MASS AND MORTALITY IN COMMUNITY-DWELLING OLDER MEN

Innovation in Aging ◽

10.1093/geroni/igz038.324 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S84-S84 ◽

Cited By ~ 4

Author(s):

Peggy M Cawthon ◽

Terri Blackwell ◽

Steven R Cummings ◽

Eric S Orwoll ◽

Kate A Duchowny ◽

...

Keyword(s):

Risk Factor ◽

Muscle Mass ◽

Proportional Hazards ◽

Smoking Status ◽

Older Men ◽

Community Dwelling ◽

Adverse Health Outcomes ◽

Injurious Falls ◽

Clinical Center ◽

Mortality Outcome

Abstract We have shown that men with low muscle mass assessed by D3Cr (deuterated creatine) dilution are more likely to have worse physical performance and incident fractures, injurious falls and disability. However, the relation between D3Cr muscle mass and mortality is unknown. With data from Year 14 Visit of the MrOS study (N=1400, mean age 84.2 yrs), proportional hazards models estimated the risk of mortality (hazard ratio and 95% CI) by quartiles of D3Cr muscle mass (standardized to body mass); we calculated p for trend across quartiles. Models were adjusted for age, race, clinical center, alcohol use, smoking status, comorbidities, activity, percent fat, exhaustion, and cognitive function. Cause of death was centrally adjudicated. Over 3.3±0.8 years of follow-up, 197 (14.1%) men died. Men in the lowest quartile of D3Cr muscle mass/wgt were 2.8-fold more likely to die than men in the highest quartile (HR: 2.8, 95% CI: 1.6, 4.9; p for trend<.001). The HRs for each cause-specific mortality outcome were of similar magnitude to the HR for overall mortality: cancer death (HR, Q1 vs Q4: 2.2, 95% CI: 0.7, 7.1; p trend =0.140); CVD death (HR, Q1 vs Q4: 3.7, 95% CI: 1.3, 10.5; p trend =0.008); or non-cancer non-CVD death (HR, Q1 vs Q4: 2.4, 95% CI: 1.0, 5.6; p trend=0.019). We conclude that low muscle mass assessed by D3Cr dilution is a strong risk factor for mortality in older men, providing additional evidence that low muscle mass is an important risk factor for adverse health outcomes.

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Associations Between Muscle Mass, Muscle Morphology and Bone Health in Older Men With Sarcopenia: A Cross-sectional Study

10.21203/rs.3.rs-66725/v1 ◽

2020 ◽

Author(s):

Asta Mastaviciute ◽

Justina Kilaite ◽

Donatas Petroska ◽

Arvydas Laurinavičius ◽

Marija Tamulaitiene ◽

...

Keyword(s):

Bone Mineral Density ◽

Muscle Mass ◽

Physical Performance ◽

Bone Mineral ◽

Muscle Fiber ◽

Lean Mass ◽

Older Men ◽

Mineral Density ◽

Balance Test ◽

Cross Sectional

Abstract Background: The aim of this study was to explore the association between muscle mass, morphology, bone mineral density, and physical function in community-dwelling older men with sarcopenia.Methods: A total of 151 men, 60 years or older were included in this study. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Low bone mineral density was diagnosed if T-score was equal to or below -1.0 SD of mean young men reference range. Sarcopenia was diagnosed according to European Working Group on Sarcopenia in Older People (EWGSOP) criteria: low muscle mass and low muscle strength or low physical performance. Physical performance was evaluated by short physical performance battery. Microbiopsy of musculus vastus lateralis was performed with disposable muscle microbiopsy system. The perimeter and cross-section area of muscle fibers were calculated using image analysis software in whole slide images; type of fiber and their distribution were evaluated as well. Relationship between variables were examined using Spearman’s and Pearson’s correlations. The level of significance (p-value) of < 0.05 was considered as statistically significant.Results: Mean age of the subjects was 72.9 ± 8.02 years. Sarcopenia was diagnosed in 45 (29.8%) men. In the sarcopenia group, 25 muscle biopsies were examined. The average muscle fiber length was 217.47 ± 25.22 microm and average fiber cross-sectional area was 2446 ± 608.87 microm2. In 9 sarcopenic men with T-scores equal or below -2.5, the muscle fiber area had a significant correlation with balance test (r = 0.73, p = 0.025). Multiple significant correlations were found between bone mineral density, lean mass, appendicular lean mass, arm and leg lean mass, gait speed, balance test and handgrip strength.Conclusions: In men with sarcopenia, low lean muscle mass was associated with low femoral neck and hip BMD, and lower muscle strength. In sarcopenic men with osteoporosis, lower muscle fiber area was associated with lower scores of balance test.Trial registration: study protocol has been approved by Lithuanian regional biomedical research ethics committee (No. 158200-03-208-75).

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Sarcopenia and homocysteine: is there a possible association in the elderly? A narrative review

Nutrition Research Reviews ◽

10.1017/s095442242100010x ◽

2021 ◽

pp. 1-36

Author(s):

Rachele De Giuseppe ◽

Chiara Elena Tomasinelli ◽

Alessandra Vincenti ◽

Ilaria Di Napoli ◽

Massimo Negro ◽

...

Keyword(s):

Muscle Strength ◽

Muscle Mass ◽

Physical Performance ◽

Working Group ◽

The Elderly ◽

Adverse Outcomes ◽

Narrative Review ◽

Increased Risk ◽

European Working ◽

Muscle Homeostasis

Abstract Background Sarcopenia (SA) is a progressive skeletal muscle disorder, associated with increased risk of adverse outcomes, including falls, fractures, physical disability and mortality. Several risks factors may contribute to the development of SA in the elderly; among them, nutrition plays a key role in muscle health. The elderly are at risk of inadequate intake in terms of micronutrients affecting muscle-homeostasis, such as B vitamins, related to homocysteine (Hcy) metabolism. Objectives and Methods This narrative review analysed the association between increased Hcy levels and SA, according to the criteria of the International Working Group on Sarcopenia, the European Working Group on Sarcopenia in Older People and the Asian Working Group for Sarcopenia. The authors focused not only on SA per se but also on exploring the association between increased Hcy levels and components of SA, including muscle mass, muscle strength and physical performance. Results Results are inconsistent, except for muscle mass, showing no significant associations with Hcy levels. Conclusions Few and conflicting data emerged in this review on the association between SA and increased Hcy levels due to numerous differences between studies that change the significance of the association of Hcy and SA, as well as with the muscle strength, muscle mass and physical performance. Furthermore, because the ageing process is not uniform in the population due to differences in genetics, lifestyle and general health, chronological age fails to address the observed heterogeneity among the "elderly" of the studies reported in this revision. Therefore, further studies are still needed.

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CT muscle density, D3Cr muscle mass and body fat associations with physical performance, mobility outcomes and mortality risk in older men

The Journals of Gerontology Series A ◽

10.1093/gerona/glab266 ◽

2021 ◽

Author(s):

Eric Orwoll ◽

Terri Blackwell ◽

Steven R Cummings ◽

Jane A Cauley ◽

Nancy E Lane ◽

...

Keyword(s):

Muscle Mass ◽

Physical Performance ◽

Body Fat ◽

Older Men ◽

Adverse Outcomes ◽

Additional Contribution ◽

Muscle Density ◽

Risk Of Death ◽

Total Body Fat ◽

Total Body

Abstract Background Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat vs. muscle fat to adverse outcomes have been unclear. Methods In a large cohort of older men (N= 1017), we measured muscle mass (D3 creatine dilution), muscle density (high resolution peripheral computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years. Results In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% CI: 0.74, 0.70), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively. Conclusions Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

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Diabetes and Heart Failure: Is it Hyperglycemia or Hyperinsulinemia?

Current Vascular Pharmacology ◽

10.2174/1570161117666190408164326 ◽

2020 ◽

Vol 18 (2) ◽

pp. 148-157 ◽

Cited By ~ 3

Author(s):

Triantafyllos Didangelos ◽

Konstantinos Kantartzis

Keyword(s):

Heart Failure ◽

Insulin Treatment ◽

Close Association ◽

Adverse Outcomes ◽

Negative Effects ◽

Beneficial Effects ◽

Appropriate Treatment ◽

Increased Risk ◽

Treatment Of Diabetes

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.

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Body composition in childhood: effects of normal growth and disease

Proceedings of The Nutrition Society ◽

10.1079/pns2003261 ◽

2003 ◽

Vol 62 (2) ◽

pp. 521-528 ◽

Cited By ~ 38

Author(s):

J. C. K. Wells

Keyword(s):

Body Composition ◽

Childhood Obesity ◽

Fat Mass ◽

Lean Mass ◽

Normal Weight ◽

Fat Free Mass ◽

General Interest ◽

Childhood And Adolescence ◽

Adult Disease ◽

Increased Risk

Body composition in children is of increasing interest within the contexts of childhood obesity, clinical management of patients and nutritional programming as a pathway to adult disease. Energy imbalance appears to be common in many disease states; however, body composition is not routinely measured in patients. Traditionally, clinical interest has focused on growth or nutritional status, whereas more recent studies have quantified fat mass and lean mass. The human body changes in proportions and chemical composition during childhood and adolescence. Most of the weight gain comprises lean mass rather than fat. In general, interest has focused on percentage fat, and less attention has been paid to the way in which lean mass varies within and between individuals. In the general population secular trends in BMI have been widely reported, indicating increasing levels of childhood obesity, which have been linked to reduced physical activity. However, lower activity levels may potentially lead not only to increased fatness, but also to reduced lean mass. This issue merits further investigation. Diseases have multiple effects on body composition and may influence fat-free mass and/or fat mass. In some diseases both components change in the same direction, whereas in other diseases, the changes are contradictory and may be concealed by relatively normal weight. Improved techniques are required for clinical evaluations. Both higher fatness and reduced lean mass may represent pathways to an increased risk of adult disease.

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Abstract P377: Insulin, Muscle Mass and Exercise Performance in Overweight Women

Circulation ◽

10.1161/circ.125.suppl_10.ap377 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Benjamin Leon ◽

Andrea Carnie ◽

Shannon Jenkins ◽

Kevin Smith ◽

Gloria Zalos ◽

...

Keyword(s):

Skeletal Muscle ◽

Upper Extremity ◽

Muscle Mass ◽

Fat Mass ◽

Lean Mass ◽

Exercise Performance ◽

Plasma Insulin ◽

Fasting Insulin ◽

Load Bearing ◽

Skeletal Mass

Introduction Obesity is associated with many negative health impacts, including hyperinsulinemia and reduced exercise performance, despite being associated with greater lean skeletal mass which works as the insulin-targeting and exercising organ. Purpose of Study We delineated the associations amongst cardiorespiratory capacity, fat mass, skeletal mass distributions, and fasting plasma insulin in overweight, non-diabetic women. Methods One hundred and seventy-two sedentary women, age 22 to 68 years (range), body mass index (BMI) (34.2 ± 6.3 [mean ± SD]; range 25.3 to 57.6 kg/m 2 ), underwent dual energy x-ray absorptiometry for body composition, fasting insulin, and graded treadmill exercise test using the Bruce protocol with measurement of oxygen consumption (peak VO 2 ). Results After adjustment for age, fasting insulin (9.8 ± 8.1; range 1.9 to 47.6 mcU/ml) was positively associated with BMI (r = 0.43, p<0.001), fat mass (r = 0.41, p< 0.001), load-bearing skeletal muscle mass (lower extremity lean mass; r = 0.29, p< 0.001), and non-load-bearing skeletal muscle mass (upper extremity lean mass; Figure, Panel A). By multiple regression analysis with age, fat mass and lower and upper extremity lean masses as covariates, fat mass, age and upper extremity lean mass (Figure, Panel B) were independent negative predictors of peak VO 2 (all p< 0.01). Lower extremity, however, trended to be positively predictive of peak VO 2 (p = 0.067). Conclusions In non-load-bearing muscle, increased lean mass associated with elevated plasma insulin is predictive of reduced oxygen consumption during exercise, suggesting additional load that may diminish cardiorespiratory exercise performance or intrinsic impairment in skeletal muscle function. In load-bearing muscle, compensatory hypertrophy due to increased fat and lean mass loads may preserve exercise performance.

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Individual and joint trajectories of change in bone, lean mass and physical performance in older men

BMC Geriatrics ◽

10.1186/s12877-020-01560-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peggy M. Cawthon ◽

Neeta Parimi ◽

Lisa Langsetmo ◽

Jane A. Cauley ◽

Kristine E. Ensrud ◽

...

Keyword(s):

Physical Performance ◽

Lean Mass ◽

Older Men ◽

Trajectories Of Change

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The Widowhood Effect: Explaining the Adverse Outcomes After Spousal Loss Using Physiological Stress Theories, Marital Quality, and Attachment

The Family Journal ◽

10.1177/1066480720929360 ◽

2020 ◽

Vol 28 (3) ◽

pp. 241-246 ◽

Cited By ~ 3

Author(s):

Jeffrey Ennis ◽

Umair Majid

Keyword(s):

Health Outcomes ◽

Marital Quality ◽

Physiological Stress ◽

Adverse Outcomes ◽

Loved One ◽

Spousal Loss ◽

Adverse Health Outcomes ◽

Physical Health Outcomes ◽

Risk Of Mortality ◽

Increased Risk

The loss of a loved one is one of the most ubiquitous life experiences. There have been multiple reviews that have found adverse health outcomes for individuals experiencing spousal loss, particularly the widowhood effect that characterizes an increased risk of mortality after loss. However, there is a lack of clarity on the relationship between physiological stress and the widowhood effect. This commentary uses the literature on stress, marital quality, and attachment to explain the widowhood effect and other adverse physical health outcomes. We discuss three points: (1) the chronic nature of stress may be the source of adverse outcomes, (2) the quality and quantity of available resources may moderate the effects of stress, and (3) the level and style of attachment may explain why these outcomes may persist many years after spousal loss.

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Sarcopenia and its components in adult renal transplant recipients: prevalence and association with body adiposity

British Journal Of Nutrition ◽

10.1017/s0007114519002459 ◽

2019 ◽

Vol 122 (12) ◽

pp. 1386-1397 ◽

Cited By ~ 3

Author(s):

Ana Paula Medeiros Menna Barreto ◽

Maria Inês Barreto Silva ◽

Karine Scanci da Silva Pontes ◽

Mariana Silva da Costa ◽

Kelli Trindade de Carvalho Rosina ◽

...

Keyword(s):

Renal Transplant ◽

Muscle Mass ◽

Physical Performance ◽

Muscle Function ◽

Adverse Outcomes ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Cross Sectional ◽

Body Adiposity ◽

European Working

AbstractSarcopenia is a progressive and generalised skeletal muscle disorder associated with adverse outcomes. Ageing causes primary sarcopenia, while secondary causes include chronic kidney disease (CKD), long-term use of glucocorticoids and obesity. The aim of the present study was to evaluate the prevalence of sarcopenia using guidelines recommended by the European Working Group on Sarcopenia in Older People (EWGSOP, 2010; EWGSOP2, 2018) and the Foundation of the National Institutes of Health (FNIH) and analyse the relationship between sarcopenia and body adiposity in adult renal transplant recipients (RTR). This was a cross-sectional study of adult RTR (BMI ≥ 18·5 kg/m2). Body composition was evaluated by dual-energy X-ray absorptiometry (DXA) and anthropometry. Glomerular filtration rate was estimated (eGFR) by CKD-Epidemiology Collaboration equation. The prevalence of sarcopenia in adult RTR (n 185; 57 % men, 50 (se 0·82) years and eGFR 55·80 (se 1·52) ml/min) was 7 % (FNIH), 11 % (EWGSOP2) and 17 % (EWGSOP). Low muscle mass, muscle function and physical performance affected, respectively, up to 28, 46 and 10 % of the participants. According to EWGSOP and EWGSOP2, body adiposity evaluated by anthropometry and DXA (percentage trunk fat) was lower in participants with sarcopenia. Conversely, according to the FNIH criteria, RTR with sarcopenia presented higher waist:height ratio. The present study suggests that adult RTR sarcopenia prevalence varies according to the diagnostic criteria; low muscle mass, low muscle function and low physical performance are common conditions; the association of body adiposity and sarcopenia depends on the criteria used to define this syndrome; and the FNIH criteria detected higher adiposity in individuals with sarcopenia.

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