Appendicular Lean Mass Index Research Articles

DNA methylation of insulin signaling pathways is associated with HOMA2-IR in primary myoblasts from older adults

BackgroundWhile ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.MethodsWe measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated cytosine phosphate guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR, an index for the assessment of insulin resistance, and levels of glycated hemoglobin HbA1c.ResultsThirty-eight dmCpGs (false discovery rate (FDR) < 0.05) were associated with HOMA2-IR, with dmCpGs enriched in genes linked with JNK, AMPK and insulin signaling. The methylation signal associated with HOMA2-IR was attenuated after the addition of either BMI (6 dmCpGs), appendicular lean mass index (ALMi) (7 dmCpGs), grip strength (15 dmCpGs) or gait speed (23 dmCpGs) as covariates in the model. There were 8 DMRs (Stouffer < 0.05) associated with HOMA2-IR, including DMRs within T-box transcription factor (TBX1) and nuclear receptor subfamily-2 group F member-2 (NR2F2); the DMRs within TBX1 and NR2F2 remained associated with HOMA2-IR after adjustment for BMI, ALMi, grip strength or gait speed. Forty-nine dmCpGs and 21 DMRs were associated with HbA1c, with cg13451048, located within exoribonuclease family member 3 (ERI3) associated with both HOMA2-IR and HbA1c. HOMA2-IR and HbA1c were not associated with accelerated epigenetic ageing.ConclusionsThese findings suggest that insulin resistance is associated with differential DNA methylation in human primary myoblasts with both muscle mass and body composition making a significant contribution to the methylation changes associated with IR.

Appendicular lean mass index changes in patients with Duchenne muscular dystrophy and Becker muscular dystrophy.

Mutations in the 79 exons of the dystrophin gene result in muscle wasting and weakness of varying clinical severity, ranging from severe/typical Duchenne muscular dystrophy (DMD) to intermediate DMD and mild Becker muscular dystrophy (BMD), depending on the frameshift of the mutation. We previously reported that males with DMD have progressively declining appendicular lean mass (ALM) and ALM index (ALMI) with age and worsening functional motor ability compared with healthy controls. These indices have not been studied in patients with intermediate DMD and BMD phenotypes and across DMD genotypes. In this study, we compared age-related trajectories of ALM and ALMI of patients who had (1) BMD without functional mobility deficits with patients who had DMD at different stages of disease and healthy controls; (2) a DMD intermediate phenotype with patients who had a typical DMD phenotype; and (3) DMD categorized by genotype. We conducted a retrospective review of ALM and ALMI data from 499 patients (ages 5-23years) with DMD (466 typical and 33 intermediate) and 46 patients (ages 5-21years) with BMD (without functional mobility deficits and functional mobility score of 1). Patients were grouped according to age reflecting disease stage (ages 5 to <7, 7 to <10, 10 to <14, and 14 to <20years) and genotype (mutations in exons 1-30, 31-44, 45-62, and 63-79). ALM and ALMI trajectories of patients with BMD paralleled those of healthy controls until adolescence, in contrast to patients with DMD. ALMI Z-scores of patients with BMD remained within ±2 SD without decline while those of patients with DMD fell below -2 SD around age 12years. Patients with BMD had increasing ALM and ALMI with age, with peak accrual between ages 10 to <14years. ALMI declined after age 14years for those with intermediate DMD compared with 10years for patients with typical DMD. Patients with mutations in exons 63-79 had a greater decline in ALMI as compared with those with other genotypes after age 10years. Age-related changes in ALMI in patients with BMD and intermediate DMD differ from those with typical DMD, reflecting their clinical phenotypes. ALM and ALMI should be further studied in patients with BMD and DMD subtypes for their potential value as surrogate markers to characterize the severity of BMD and DMD and inform clinical care decisions and clinical trial designs.

Association Between Interleukin 6 and C-Reactive Protein Serum Levels and Body Composition Compartments and Components in Breast Cancer Survivors.

Obesity is highly prevalent in breast cancer (BC) survivors. Adipose tissue promotes inflammation, affecting recurrence, morbidity, and quality of life. This study aimed to determine the relationship of body composition parameters with the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) in female BC survivors. Additionally, we evaluated the association of log-transformed serum concentrations of CRP and IL-6 with the appendicular skeletal lean mass index (ASMI). The results showed that CRP was positively associated with body fat percentage (BFP; β adjusted = .08, 95% CI: .02-.14) in all participants, and with fat mass index (FMI; β = .24, 95% CI: .08-.40) only in premenopausal women. IL-6 was positively associated with FMI (β adjusted = .16, 95% CI: .03-.29), while ASMI decreased as CRP levels increased (β adjusted = -.30, 95% CI: -.53 to -.06). Interventions to improve body composition in BC survivors should also consider the role of inflammatory markers in changes in body composition to avoid sarcopenic obesity (SO) and the risk of BC recurrence.

SAT382 Lean Mass and Associated Factors in Women with PCOS with Different Phenotypes

Abstract Disclosure: T.M. Fighera: None. B.R. Santos: None. P.M. Spritzer: None. Introduction: Obesity, insulin resistance and hyperandrogenism are common findings in women with PCOS. These abnormalities have been associated with muscle mass changes reported in previous studies, with conflicting results comparing women with PCOS versus non-PCOS controls. The aim of the present study was to evaluate clinical and laboratory variables related to lean body mass according to PCOS phenotype. METHODS: In this case-control study, we analyzed 133 women of reproductive age, recruited through public advertisement at the outpatient clinic of a University Hospital. Inclusion criteria were body mass index (BMI) ranging from 18.5 to 39.9 kg/m², age between 17 and 35 years and no intake of drugs known to interfere with hormone levels for at least 3 months before the study. Women with diabetes, thyroid dysfunction, liver or renal disease were excluded. PCOS was defined according to the Rotterdam Consensus. The study protocol was approved by the local Ethics Committee, and written informed consent was obtained from all participants. Blood pressure, BMI, body composition by dual-energy X-ray absorptiometry (DXA), and laboratory measurements for metabolic and hormonal variables were performed in all subjects. Creatinine values were used as an indirect marker of lean mass. RESULTS: Median age was 28 years (23-31), and the median BMI was 27.9kg/m² (24.1-33.7), with higher BMI in women with the AB phenotype of PCOS (n=59) compared to ovulatory (C phenotype) PCOS (n=23) and controls (n=51) (p=0.005). Women with the AB phenotype of PCOS presented higher Ferriman-Gallway score (p&amp;lt;0.001), systolic (p=0.001) and diastolic blood pressure (p=0.002), insulin levels (p=0.006), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p=0.008), metabolic syndrome prevalence (p&amp;lt;0.001), testosterone (p=0.008), free androgen index (FAI) (p&amp;lt;0.001), fat mass index (FMI) (0.015), and android-to-gynoid (AG) fat ratio (p=0.036) compared to controls. Appendicular lean mass index (ALMI) was higher in the AB phenotype than controls [7.01 (6.33-8.02) vs 6.69 (5.94-7.09), p= 0.024] and the C phenotype [6.60 (6.16-7.22), p=0.022]. A positive correlation was observed between ALMI and creatinine, even after adjustment to BMI, in women with AB phenotype (rho=0.319, p=0.023), but not with ovulatory PCOS (rho=0.293, p=0.238) or controls (rho=0.277, p=0.097). In a multivariate linear regression model, creatinine, HOMA-IR, and FMI were positively associated with ALMI, explaining 38.4% of the variation in lean mass. CONCLUSIONS: The present results suggest that the higher lean mass observed in women with the AB phenotype of PCOS is associated with hyperinsulinemia and higher fat mass. Sources of research support: INCT/CNPq and FAPERGS Presentation Date: Saturday, June 17, 2023

Lean mass and associated factors in women with PCOS with different phenotypes.

Although current evidence suggests increased risk of obesity, insulin resistance, and metabolic alterations in patients with polycystic ovary syndrome (PCOS), especially of a hyperandrogenic phenotype, the impact of each one of these variables on muscle mass remains uncertain. In this case-control study, we evaluated clinical and hormonal characteristics related to lean body mass according to the different PCOS phenotypes. We performed clinical, metabolic, and hormonal assessments and evaluated body compartments by dual-energy X-ray absorptiometry in 133 women of reproductive age. Creatinine served as an indirect marker of lean mass. Median age was 28 (range, 17-37) years. Women with phenotypes A and B (n = 59) had higher body mass index (BMI) and metabolic syndrome prevalence than those with phenotype C (n = 23) and controls (n = 51) (p<0.005). Women with phenotypes A and B also had higher Ferriman-Gallwey score (p<0.001), insulin levels (p = 0.006), HOMA-IR (p = 0.008), testosterone (p = 0.008), free androgen index (FAI) (p<0.001), fat mass index (FMI) (p = 0.015), android-to-gynoid fat ratio (p = 0.036), and bone mineral density (BMD) at lumbar spine (p = 0.027) and total femur (p = 0.013) than controls. Median appendicular lean mass index (ALMI) was higher in phenotypes A and B than in controls (7.01 [IQR, 6.33-8.02] vs. 6.69 [IQR, 5.94-7.09], p = 0.024), but it did not differ significantly from that in phenotype C (6.60 [IQR, 6.16-7.22], p = 0.222). Even after adjusting for BMI, ALMI correlated positively with creatinine in women with phenotypes A and B (rho = 0.319, p = 0.023) but not in those with phenotype C (p = 0.238) or controls (p = 0.097). In multivariate linear regression analyses, ALMI was positively associated with insulin, FAI, FMI, and total femur BMD. The present results suggest that fasting insulin, FAI, fat mass, and total femur BMD were positively associated with increased lean mass in women with PCOS phenotypes A and B.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate

BackgroundThe influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension.MethodsWe included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999–2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality.ResultsIn older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14–2.49, P = 0.008; HR 1.48, 95% CI 1.04–2.10, P = 0.028; HR 1.30, 95% CI 1.02–1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results.ConclusionsThe prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Genetic Variants, Serum 25-Hydroxyvitamin D Levels, and Sarcopenia

Vitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level >20 ng/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng/mL should be corrected, approximately 30% of the world population's 25(OH)D levels range from 10 to 20 ng/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk. To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk. This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk. A weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration. The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed. The final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated. In this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort

BackgroundBody composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. ObjectivesThis study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). MethodsThis is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5–19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. ResultsWe obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and–2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian −0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black −0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. ConclusionsThese reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

Weight variability, physical functioning and incident disability in older adults.

This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults. Included were participants from the Health, Aging and Body Composition Study who had semi-annual BMI data during the first 3years of follow-up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3-year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors. Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (β: -0.086 [95% confidence interval, CI: -0.133, -0.040], P<0.01) and fat mass (β: -0.059 [95% CI: -0.117, -0.002], P=0.04) and had greater declines in physical performance score (β: -0.094 [95% CI: -0.162, -0.026], P<0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 [95% CI: 1.07, 1.72], P=0.01), independent of net BMI change. BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.

Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, leading to chronic synovial inflammation and local tissue destruction. Extra-articular manifestations may also occur, such as changes in body composition. Skeletal muscle wasting is often observed in patients with RA, but methods for assessing loss of muscle mass are expensive and not widely available. Metabolomic analysis has shown great potential for identifying changes in the metabolite profile of patients with autoimmune diseases. In this setting, urine metabolomic profiling in patients with RA may be a useful tool to identify skeletal muscle wasting. Patients aged 40-70years with RA have been recruited according to the 2010 ACR/EULAR classification criteria. Further, the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) determined the disease activity. The muscle mass was measured by Dual X-ray absorptiometry (DXA) to generate the appendicular lean mass index (ALMI) by summing the lean mass measurements for both arms and legs and dividing them by height squared (kg/height2 ). Finally, urine metabolomic analysis by 1 H nuclear magnetic resonance (1 H-NMR) spectroscopy was performed and the metabolomics data set analysed using the BAYESIL and MetaboAnalyst software packages. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the 1 H-NMR data, followed by Spearman's correlation analysis. The combined receiver operating characteristic curve (ROC) was calculated, as well as the logistic regression analyses to establish a diagnostic model. The significance level at P<0.05 was set for all analyses. The total set of subjects investigated included 90 patients with RA. Most patients were women (86.7%), with a mean age of 56.5±7.3years old and a median DAS28-CRP of 3.0 (IQR 1.0-3.0). Fifteen metabolites were identified in the urine samples with high variable importance in projection (VIP scores) by MetaboAnalyst. Of these, dimethylglycine (r=0.205; P=0.053), oxoisovalerate (r=-0.203; P=0.055), and isobutyric acid (r=-0.249; P=0.018) were significantly correlated with ALMI. Based on the low muscle mass (ALMI ≤6.0kg/m2 for women and ≤8.1kg/m2 for men) a diagnostic model have been established with dimethylglycine (area under the curve [AUC]=0.65), oxoisovalerate (AUC=0.49), and isobutyric acid (AUC=0.83) with significant sensitivity and specificity. Isobutyric acid, oxoisovalerate, and dimethylglycine from urine samples were associated with low skeletal muscle mass in patients with RA. These findings suggest that this group of metabolites may be further tested as biomarkers for identification of skeletal muscle wasting.

Muscular involvement in long-term type 1 diabetes: Does it represent an underestimated complication?

ObjectivesStructural, metabolic, and functional signs of skeletal muscle damage have been identified in individuals affected by type 1 diabetes (T1D), but, to our knowledge, no guidelines for the diagnosis and treatment of muscle impairment exist and studies on T1D and muscle health remain limited. The aim of this study was to evaluate the prevalence of sarcopenia in a long-term T1D population and to assess the effects of some clinical parameters on muscle mass and function. MethodsThirty-nine patients affected by T1D were enrolled. Body mass index (BMI), body composition (appendicular lean mass index [ALMI] and fat mass [FM]), and muscle strength were measured. Additionally, the relationship between Mediterranean diet adherence and sarcopenia was assessed. ResultsIn the present sample (mean age 49.32 ± 13.49 y, 41.1% women, mean duration of diabetes 30.13 ± 12.28 y), the prevalence of sarcopenia was 7.7% (12.5 % in women and 4.35% in men). The prevalence of low ALMI was 23.1% (25% in women and 21.74% in men). Significant inverse correlations were found between ALMI and duration of diabetes and ALMI and FM; and significant positive correlations between ALMI and BMI, physical activity level, and muscle strength. At the same time, significant inverse correlations were observed between muscle strength and duration of diabetes and muscle strength and FM. ConclusionsWe observed a high prevalence of low muscle mass, similar to those found in the older age groups of the general population (25 years in advance) and our findings suggest a possible pathogenetic role of T1D duration on muscle trophism and function.

Handgrip Strength and Muscle Quality: Results from the National Health and Nutrition Examination Survey Database.

Handgrip strength (HGS) and the appendicular lean mass index (ALMI) are important determinants of sarcopenia. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We examined trends in handgrip strength, the appendicular lean mass index, and analyzed their relationship with age, anthropometry, and body composition in a sample of participants in the United States (US). This cross-sectional study analyzed data from 14,741 US males (49.7%) and females (50.3%) 6-80 years old who responded to the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dual X-ray absorptiometry was used to measure appendicular skeletal muscle mass. HGS was evaluated using the Takei Digital Grip Strength Dynamometer. Smoothed normative curves for HGS and the ALMI were constructed using a generalized additive model. Multiple regression analyses were used to examine associations of HGS and the ALMI with age, nutrition-related factors, physical activity, and body composition. Mean HGS and the ALMI declined with advancing age. While mean HGS increased with the ALMI, it decreased with the fat mass index. HGS increased in males with an increase in body mass index, energy intake, the ALMI, and vitamins; however, HGS in females increased with albumin, but it had a negative association with the fat mass index and age, but not with increasing adiposity. HGS and the ALMI change with age: HGS increases with age, then stabilizes and declines; the ALMI increases with age, then stabilizes. In addition, we provide evidence for the effect of anthropometry, nutrition, physical activity, and body composition on HGS and the ALMI in US population.

Associations of Mutually Exclusive Categories of Physical Activity and Sedentary Behavior with Body Composition and Fall Risk in Older Women: A Cross-Sectional Study.

The individual effects of physical activity (PA) and sedentary behavior (SB) on health are well-recognized. However, little is known about the extent to which different combinations of these behaviors are associated with body composition and fall risk in older adults. This cross-sectional study examined the associations of mutually exclusive categories of PA and SB with body composition and fall risk in older women. Accelerometer-measured PA, body composition and fall risk (static and dynamic balance) parameters were assessed among 94 community-dwelling older women. The participants were categorized into four groups: active-low sedentary, active-high sedentary, inactive-low sedentary and inactive-high sedentary (active: ≥150 min/week moderate-to-vigorous PA (MVPA); low sedentary: lowest tertile of SB and light PA ratio). Compared to the inactive-high sedentary group, more favorable body composition and dynamic balance results were found in the active-low sedentary (body fat mass index (BFMI): β = -4.37, p = 0.002; skeletal muscle mass index (SMI): β = 1.23, p = 0.017; appendicular lean mass index (ALMI): β = 1.89, p = 0.003; appendicular fat mass index (AFMI): β = -2.19, p = 0.003; sit-to-stand: β = 4.52, p = 0.014) and inactive-low sedentary (BFMI: β = -3.14, p = 0.007; SMI: β = 1.05, p = 0.014; AFMI: β = -1.74, p = 0.005, sit-to-stand: β = 3.28, p = 0.034) groups. Our results suggest that PA programs focusing on concurrently achieving sufficient MVPA and reduced SB might promote a healthy body composition and reduced fall risk among older adults.

Cystatin C and Creatinine Concentrations Are Uninformative Biomarkers of Sarcopenia: A Cross-Sectional NHANES Study

Differences in creatinine and cystatin C-based estimates of glomerular filtration rate (eGFRDiff=eGFRCr - eGFRCysC) may reflect differences in muscle mass. We sought to determine if eGFRDiff (1) reflects lean mass, (2) identifies sarcopenic individuals beyond estimates based on age, body mass index (BMI), and sex; and (3) demonstrates associations differently in those with and without chronic kidney disease (CKD). This cross-sectional study included 3,754 participants, ages 20-85years, with creatinine and cystatin C concentration levels, and dual-energy X-ray absorptiometry scans from National Health and Nutrition Examination Survey data (1999-2006). Dual-energy X-ray absorptiometry-derived appendicular lean mass index (ALMI) estimated muscle mass. Non-race-based CKD Epidemiology Collaboration equations estimated glomerular filtration rate using eGFRCr, eGFRCysC, and both biomarkers (eGFRCysC&Cr). CKD was defined as eGFRCysC&Cr<60mL/minute/1.73m2. ALMI sex-specific T-scores (compared with young adult)<-2.0 defined sarcopenia. In estimating ALMI, we compared the coefficient of determination (R2) values from: 1) eGFRDiff, 2) clinical characteristics (age, BMI, and sex), and 3) clinical characteristics plus eGFRDiff. Using logistic regression, we evaluated each model's C-statistic to diagnose sarcopenia. eGFRDiff was negatively and weakly associated with ALMI (No CKD: R2=0.006, p-value 0.002; CKD: R2=0.001, P value .9). Clinical characteristics explained most of the variation in ALMI (No CKD: R2=0.851, CKD: R2=0.828), and provided strong discrimination of sarcopenia (No CKD C-statistic: 0.950; CKD C-statistic: 0.943). Adding eGFRDiff improved the R2 by 0.025, and the C-statistic by 0.003. Tests for interaction between eGFRDiff and CKD were not significant (all P values > .05). Although eGFRDiff has statistically significant associations with ALMI and sarcopenia in univariate analyses, multivariate analyses demonstrate that eGFRDiff does not capture more information beyond routine clinical characteristics (age, BMI, and sex).

Association between low handgrip strength and obesity with mortality in peritoneal dialysis patients

The association between sarcopenia and obesity in peritoneal dialysis (PD) patients is more complex than that of the general population. The aim of this study was, therefore, to evaluate the association of patient survival with sarcopenia or sarcopenic components and obesity in groups of patients with PD. We retrospectively analyzed a dataset from 199 prevalent PD patients. Measurements including handgrip strength (HGS), appendicular lean mass index, and baseline characteristics, were obtained during the period of study. Patients were divided into four groups according to their HGS and obesity: NH-NO (normal HGS and non-obesity, n = 60), NH-O (normal HGS and obesity, n = 31), LH-NO (low HGS and non-obesity, n = 71), and LH-O (low HGS and obesity, n = 37). The median follow-up interval was 17 months. The Kaplan–Meier curve analysis showed that the LH-O group had the poorest patient survival outcome among the four groups (P < 0.001). The NH-NO group had a better patient survival outcome compared with the LH-NO group. Univariate and multivariate Cox regression analyses showed that the LH-O group had the highest mortality rate compared with the other groups. The NH-NO group had lower mortality compared with the LH-NO group. The present study demonstrated that obesity with low HGS was associated with the greatest mortality rate in groups defined by HGS and obesity.

Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia.

Ageing traits and frailty are important health issues in modern medicine. Evidence supporting the causal effects of tobacco smoking on various ageing traits is required. This study performed Mendelian randomization (MR) analysis instrumenting 377 genetic variants associated with being an ever-smoker at a genome-wide significance level to test the causal estimates from tobacco smoking. The outcome data were obtained from 337 138 white British ancestry participants from the UK Biobank. Leucocyte telomere length, appendicular lean mass index, subjective walking pace, handgrip strength,and wristband accelerometry-determined physical activity degree were collected as ageing-related outcomes. Summary-level MR analysis was performed using the inverse variance-weighted method and pleiotropy-robust MR methods, including weighted median and MR-Egger. Observational association between the outcome traits and phenotypically being an ever-smoker was also investigated. Summary-level MR analysis indicated that a higher genetic predisposition for tobacco smoking was significantly associated with shorter leucocyte telomere length (twofold increase in prevalence of smoking towards standardized Z-score, -0.041 [-0.054, -0.028]), lower appendicular lean mass index (-0.007 [-0.010, -0.005]), slower walking pace (ordinal category, -0.047 [-0.054, -0.033]) and lower time spent on moderate-to-vigorous physical activity (hours per week, -0.39 [-0.56, -0.23]). The causal estimates were non-significant towards handgrip strength phenotype (kg, 0.074 [-0.055, 0.204]). Pleiotropy-robust MR results generally supported the main causal estimates. The observational findings also showed significant association between being an ever-smoker and the ageing traits. Genetically predicted and observational tobacco smoking status are significantly associated with poor ageing phenotypes. Healthcare providers may continue to reduce tobacco use, which may be helpful in reducing the burden of ageing and frailty.

Oxylipin status, before and after LC n-3 PUFA supplementation, has little relationship with skeletal muscle biology in older adults at risk of sarcopenia

IntroductionOxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation. Materials and methodsThis exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (n = 49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined. ResultsAt baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (p = 0.003, r=-0.41), skeletal muscle mass index (SMMI) (p = 0.001, r=-0.46), handgrip strength (HGS) (p<0.001, r = 0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxy‑PUFA were negatively correlated to HGS (i.e., 12-HETrE, p = 0.002, r=-0.42, and 5- and 11-HETE, p = 0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, p = 0.006, r=-0.39 and 16-HETE, p = 0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, p = 0.006, r = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, p = 0.007, r = 0.38 and 16-HETE, p = 0.006, r = 0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters. Discussion and conclusionAt baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology.

Recent sarcopenia definitions-prevalence, agreement and mortality associations among men: Findings from population-based cohorts.

The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27kg and ALM index <7.0kg/m2 ), SDOC (grip strength <35.5kg and gait speed <0.8m/s) and Modified SDOC (grip strength <35.5kg and gait speed <1.0m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. Mean (SD) age of participants (n=9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ=0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2 : 0.0%]; SDOC [2.75 (2.28, 3.31), I2 : 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2 : 58.3%]. There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.

Frequency and Functional Consequences of Low Appendicular Lean Mass and Sarcopenic Obesity in Patients with Asthma Referred for Pulmonary Rehabilitation

Introduction: One of the most prominent extrapulmonary manifestations in patients with chronic respiratory disease is changes in body weight and composition. However, the frequency and functional consequences of low appendicular lean mass (ALM) or sarcopenic obesity (SO) in patients with asthma are largely unknown. Therefore, the aim of the current study was to assess the frequency and functional consequences of low appendicular lean mass index (ALMI) and SO in patients with asthma. Methods: A retrospectively analyzed cross-sectional study was conducted in 687 patients with asthma (60% female, 58 ± 13 years, FEV₁ 76 ± 25% pred) referred for comprehensive pulmonary rehabilitation (PR). Body composition, pulmonary function, exercise capacity, quadriceps muscle function, and quality of life were assessed. Patients were classified as presenting low ALMI according to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values and as having SO according to the diagnostic procedure proposed by the 2022 ESPEN/EASO consensus. In addition, clinical outcomes between patients with normal and low ALMI or with and without SO were compared. Results: The frequency of patients classified as low ALMI was 19%, whereas 45% of the patients were obese. Among the obese patients, 29% had SO. In patients with normal weight, those with low ALMI were younger and had worse pulmonary function, exercise capacity and quadriceps muscle function than those with normal ALMI (all p < 0.05). Overweight patients with low ALMI presented poorer pulmonary function and quadriceps muscle function (both strength and total work capacity). In obese class I patients, those with low ALMI showed lower quadriceps strength and maximal oxygen uptake acquired during cardiopulmonary exercise testing. Both male and female patients with SO showed lower quadriceps muscle function and reduced maximal exercise capacity compared to non-SO asthma patients. Conclusion: Approximately one in five asthma patients presented low ALM when age-sex-BMI-specific ALMI cutoffs were applied. Obesity is common among patients with asthma referred for PR. Among the obese patients, a significant proportion presented SO. Low ALM and SO were associated with worse functional outcomes.

INFLUENCE OF TOTAL KNEE REPLACEMENT ON LEAN MASS MEASUREMENTS USING DUAL-ENERGY X-RAY ABSORPTIOMETRY

Abstract Sarcopenia and osteoarthritis often occur together. Many sarcopenic patients with osteoarthritis are managed by total knee replacement (TKR). The prevalence of TKR is increasing in older adults; however, metal implants can lead to the overestimation of lean mass (LM) in dual-energy X-ray absorptiometry (DXA). However, studies considering metal implants in DXA measurement of LM are scarce. Comparisons without and with automatic metal detection (AMD) are important for accurately measuring LM. Therefore, this study examined the effects of TKR on LM. Twenty-four subjects (mean age: 76.4±4.0 years) who underwent TKR were selected from the Korean Frailty and Aging Cohort Study. A GE Lunar iDXA (GE Healthcare Lunar, Madison, WI, USA) system was applied twice (with and without AMD). Leg LM was significantly overestimated in the right and left legs with TKR. The LMs with and without AMD were 6017.1±199.3 g and 5493.7±171.3 g, respectively (p&amp;lt; 0.001), in the right leg, and 5657.1±220.1 g vs. 5173.7±201.8 g, respectively (p&amp;lt; 0.001) in the left leg. The appendicular lean mass index (ALMI) without and with AMD was 6.5±0.6 kg/m2, 6.1±0.6 kg/m2 (p&amp;lt; 0.001). In addition, only one subject was classified as having low muscle mass without AMD, which increased to four based on AMD according to the Asian Working Group of Sarcopenia 2019 guidelines. The overestimated leg LM in subjects after TKR decreased with AMD. Furthermore, LM with AMD increased the prevalence of low appendicular LM in the diagnosis of sarcopenia. Therefore, metal implants should be considered to accurately measure LM using DXA.