Muscle Mass Research Articles

The prognostic value of skeletal muscle mass and density in breast cancer: a systematic review and meta-analysis.

Aim: The effect of skeletal muscle mass and density on the long-term survival outcome of breast cancer patients is unclear.Materials & methods: Systematically searched all articles in PubMed, Web of science, Springerlink, EMBASEand Wiley databases that studied the association between skeletal muscle and survival outcomes of breast cancer by 25September 2023. The hazard ratios and confidence intervals of the multiple factor analysis results controlling for confounding variables in the study were collected and analyzed using STATA 14.0 software.Results: This meta-analysis included a total of 13 studies, with a median age of 48.2years. Meta results showed that the survival (hazard ratio [HR]: 0.98, 95% CI: 0.89-1.08) and recurrence (HR: 0.96, 95% CI: 0.92-1.00) outcomes of breast cancer patients with sarcopenia were not significantly affected compared with those without sarcopenia. No significant heterogeneity or publication bias was observed in the study.Conclusion: The conclusion that skeletal muscle is regarded as a useful factor that can guide and optimize the prognosis of breast cancer patients is uncertain, or the result is very weak. Considering the impact of research quality and confounding factors, prospective studies are needed in the future to further demonstrate.PROSPERO identifier: CRD42023463480 (www.crd.york.ac.uk/prospero).

Secondary Sarcopenia in Patients with Locomotor Disorders: Prevalence, Diagnosis and Medical Rehabilitation. A Review

INTRODUCTION. The development of rehabilitation methods for patients with sarcopenia, a generalized age-associated loss of skeletal muscle mass and strength, is important, since sarcopenia leads to pronounced weakness, functional and motor disorders and an increased risk of death in the elderly. AIM. To analyze the prevalence, features of pathogenesis, diagnosis of secondary sarcopenia, including against the background of motor disorders due to stroke, as well as methods of treatment and medical rehabilitation of such patients. MAIN CONTENT. Among the secondary forms, sarcopenia is of the greatest clinical importance against the background of the consequences of acute cerebrovascular accident (ACA), due to muscular atrophy associated with paralysis and immobility, spasticity, inflammation and denervation of muscles, malnutrition and intestinal absorption of protein and vitamin D. Recent studies show that the prevalence of sarcopenia in stroke patients in emergency hospitals is 8.5–33.8 %, according to other data — more than 42 %. Muscle weakness after a stroke contributes to a decrease in physical functions and the development of disability, and sarcopenia leads to adverse outcomes 90 days after a stroke. According to the meta-analysis, which included 7 cohort studies with a total sample of 1,774 patients who underwent ACA, 27.1 % of them had sarcopenia. Moreover, the presence of sarcopenia negatively affected the clinical and functional outcomes of ACA, as well as the results of medical rehabilitation (odds ratio: 2.42, 95 % confidence interval: 1.76–3.33, p 0.001). CONCLUSION. Despite the prevalence and relevance of this pathology, rehabilitation programs for patients with sarcopenia against the background of the consequences of ACA have not been developed. Isolated foreign publications demonstrate the effectiveness of certain methods of physical therapy and electrical stimulation, but the evidence base for their effectiveness is low.

Evaluating the SarQoL® Questionnaire as a Screening Tool for Sarcopenia among Korean Older Adults.

Sarcopenia, characterized by the progressive loss of muscle mass and strength, poses significant risks to physical health, leading to a reduced quality of life (QoL), increased disability, and higher mortality rates among older adults. Early detection and intervention are crucial to prevent the cascading effects of sarcopenia, including falls, fractures, and hospitalization. This study determined an optimal cut-off point of the SarQoL® score that can serve as an effective screening tool among community-dwelling Korean older adults. The study involved 451 South Korean older adults, assessing the correlation between SarQoL® scores and sarcopenia as defined by the Asian Working Group for Sarcopenia (AWGS) criteria. Participants completed the Korean version of the SarQoL questionnaire. Findings revealed that individuals diagnosed with sarcopenia had significantly lower SarQoL® scores compared to non-sarcopenic participants, with a cut-off score of ≤58.5 providing good diagnostic accuracy (AUC = 0.768, sensitivity = 69.3%, specificity = 75.2%). These results underscore the questionnaire's reliability and validity in screening for sarcopenia-related QoL impairment and its potential utility as a clinical tool. Implementing the SarQoL® in routine assessments could improve clinical outcomes by enabling earlier and more precise identification of sarcopenia.

Effects of age on human skeletal muscle: A systematic review and meta-analysis of myosin heavy chain isoform protein expression, fiber size and distribution.

Human studies examining the cellular mechanisms behind sarcopenia, or age-related loss of skeletal muscle mass and function, have produced inconsistent results. A systematic review and meta-analysis were performed to determine the aging effects on protein expression, size and distribution of fibers with various myosin heavy chain (MyHC) isoforms. Study eligibility included MyHC comparisons between young (18-49 years) and older (≥ 60 years) adults, with 27 studies identified. Relative protein expression was higher with age for the slow-contracting MyHC I fibers, with correspondingly lower fast-contracting MyHC II and IIA values. Fiber sizes were similar with age for MyHC I, while smaller for MyHC II and IIA. Fiber distributions were similar with age. When separated by sex, the few studies that examined females showed atrophy of MyHC II and IIA fibers with age, but no change in MyHC protein expression. Additional analyses by measurement technique, physical activity, and muscle biopsied provided important insights. In summary, age-related atrophy in fast-contracting fibers lead to more of the slow-contracting, lower force-producing isoform in older male muscles, which helps explain their age-related loss in whole muscle force, velocity, and power. Exercise or pharmacological interventions that shift MyHC expression towards faster isoforms and/or increase fast-contracting fiber size should decrease the prevalence of sarcopenia. Our findings also indicate that future studies need to include or focus solely on females, measure MyHC IIA and IIX isoforms separately, examine fiber type distribution, sample additional muscles to the vastus lateralis, and incorporate an objective measurement of physical activity.

Advancements in Drug Delivery Systems for the Treatment of Sarcopenia: An Updated Overview.

Since sarcopenia is a progressive condition that leads to decreased muscle mass and function, especially in elderly people, it is a public health problem that requires attention from researchers. This review aims to highlight drug delivery systems that have a high and efficient therapeutic potential for sarcopenia. Current as well as future research needs to consider the barriers encountered in the realization of delivery systems, such as the route of administration, the interaction of the systems with the aggressive environment of the human body, the efficient delivery and loading of the systems with therapeutic agents, and the targeted delivery of therapeutic agents into the muscle tissue without creating undesirable adverse effects. Thus, this paper sets the framework of existing drug delivery possibilities for the treatment of sarcopenia, serving as an inception point for future interdisciplinary studies.

Adjusting dialysis dose (Kt) scaled to Body Surface Area (BSA) could be a more logical approach.

The dialysis dose, quantified as Kt, is conventionally scaled to the urea distribution volume (V) to calculate the Kt/V ratio as an indicator of dialysis adequacy. However, the body surface area (BSA) is recognized as a more accurate reflection of metabolic activity compared to V. This study presents evidence supporting the enhanced efficacy of the Kt/BSA ratio as an indicator of hemodialysis adequacy. The study population comprised 211 individuals undergoing hemodialysis, all of whom had Kt/V values determined. Body composition was assessed using bioimpedance techniques, and BSA was calculated employing the DuBois and DuBois formula. The ratio of V/BSA served as the conversion factor to derive Kt/BSA from the standard Kt/V. Participants were categorized by gender, and a comparative analysis was performed on dialysis-related parameters alongside body composition indicators. Concurrently, linear regression analysis was applied to Kt/V and Kt/BSA, as well as to pairs of V and BSA, to elucidate the relationships among these variables. The average Kt/V ratio was 1.50 with a standard deviation of 0.28. The Kt/V ratio was significantly higher in women (P < 0.01). Conversely, the Kt value, when not adjusted for body size, was significantly lower in women (P < 0.01). Upon scaling Kt to BSA to calculate Kt/BSA, the gender difference in dialysis dose adequacy was no longer statistically significant (P = 0.06). Men exhibited a significantly higher mean V/BSA ratio. Additionally, women had a slightly higher mean percentage of fat mass (P < 0.01). In contrast, women had a lower mean percentage of muscle mass (P < 0.01). Our findings suggest that the Kt/V ratio may underestimate the required hemodialysis dose for women. There was no gender difference when Kt scaling to BSA. Consequently, the Kt/BSA ratio, which accounts for body surface area, may play a significant role in more accurately scaling the hemodialysis dose.

Low Serum Alanine Aminotransferase Blood Activity Is Associated with Shortened Survival of Renal Cell Cancer Patients and Survivors: Retrospective Analysis of 1830 Patients

Background: Sarcopenia is characterized by a loss of muscle mass and function and is often associated with frailty, a syndrome linked to physical disability and shortened survival in various patient populations, including cancer patients. Low serum alanine aminotransferase (ALT) values, serving as a biomarker for sarcopenia, were previously associated with frailty and shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods: This was a retrospective analysis of RCC patients and survivors, both in- and outpatients. We defined patients with sarcopenia as those presenting with ALT &lt; 17 IU/L. Results: We identified records of 3012 RCC patients. The cohort included 1830 patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3%) had ALT &lt; 17 IU/L, with a mean ALT value of patients within the low-ALT group of 11.79 IU/L, while the mean value in the higher ALT level group was 24.44 IU/L (p &lt; 0.001). Patients in the low-ALT group were older (67.9 vs. 63.7 years; p &lt; 0.001) and had lower BMIs (26.6 vs. 28; p &lt; 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p &lt; 0.001), higher serum creatinine (1.49 vs. 1.14; p &lt; 0.001) and higher platelet to lymphocyte ratios (178 vs. 156; p &lt; 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46–2.02, p &lt; 0.001). In a multivariate model controlled for age, gender, hemoglobin, platelets, LDH, neutrophil to lymphocyte ratios and platelet to lymphocyte ratios, low ALT levels were still associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08–1.51; p = 0.005). Conclusion. Low ALT values, associated with sarcopenia and frailty, are also associated with shortened survival in RCC patients, and survivors and could potentially be applied for optimizing individual treatment decisions.

A Systematic Review of the Impact of Vegetarian Diets on Muscle Mass and Muscle Strength in Community‐Dwelling, Healthy Adults

ABSTRACTBackgroundLoss of muscle mass and muscle strength are key characteristics of age‐related muscle decline. Dietary protein is a key nutrient that supports optimal muscle health. However, there is a strong argument to reduce intake of animal protein for health and environmental reasons. The effects of vegetarian diets on determinants of muscle health are not clear. This systematic review aimed to investigate the impact of vegetarian diets on muscle mass and muscle strength.MethodsA systematic literature search of the CINAHL, Medline, Scopus and Web of Science Core Collection databases, as well as the Cochrane Central Register of Controlled Trials, was conducted according to PRISMA guidelines. Studies reporting the effects of vegetarian diets on muscle mass and strength were analysed.ResultsA total of three interventions and 11 observational studied were eligible to be included (n = 14) in this review. Five of the 12 studies that reported muscle mass found no difference in muscle mass between participants consuming an omnivorous versus vegetarian diet. One observational study reported higher muscle mass for vegetarians. Of the studies that reported muscle strength (n = 5), three reported no difference between participants consuming an omnivorous and vegetarian diet.ConclusionsHalf of the included studies reported no difference in muscle mass or strength between vegetarians and omnivores. Further high‐quality studies are needed to better understand the relationship between vegetarian diets and determinants of muscle health.

7785 Muscle Strength and Physical Performance Are Closely Related to Muscle Quality Regardless of Muscle Mass or Diabetes Status

Abstract Disclosure: J. Seo: None. I. Jung: None. S. Park: None. D. Lee: None. J. Yu: None. H. Cho: None. K. Kim: None. E. Song: None. K. Kim: None. N. Kim: None. H. Yoo: None. S. Kim: None. K. Choi: None. N. Kim: None. C. Shin: None. Weakness or slowness is essential to define sarcopenia rather than less muscle mass. Myosteatosis is associated with low muscle strength and poor physical performance, and ectopic fat deposition is a characteristic of diabetes (DM). We investigated the association between muscle strength/physical performance and myosteatosis by considering DM status and muscle mass in community-dwelling older adults. A total of 982 subjects (447 men and 535 women) aged 54-83 years in 8th examination of the Korean Genome and Epidemiology Study Ansan cohort participated in this study. Handgrip strength (HSG), 4-m walking velocity (VEL) and 30-Seconds Sit-to-Stand Test (STST) were checked, appendicular skeletal muscle mass (ASM) and total muscle mass (TMM) by DXA were measured. In midthigh CT image, total muscle area (TMA) was measured and categorized into 3 components using Hounsfield Unit (HU): normal-attenuation muscle area (NAMA, 35-100HU), low-attenuation muscle area (LAMA, 0-34HU), and inter/intramuscular adipose tissue (IMAT) area. As muscle quality indices, the NAMA index, LAMA index, and IMAT index were defined by dividing each parameter by TMA. DM was diagnosed by fasting glucose ≥126 mg/dL, 2hr-OGTT glucose ≥200 mg/dL, HbA1c ≥6.5% or anti-diabetic medication. Subjects with DM (38% of total subjects) had higher age and body mass index (BMI) compared to non-DM subjects. Prevalence of low muscle mass (M:&amp;lt;7.0kg/m2, F:&amp;lt;5.4kg/m2 of ASM/height2) was not statistically different by the presence of DM (DM vs non-DM, 11.7% vs 9.7% in men, 3.6% vs 7.6% in women). However, prevalence of low HGS (M:&amp;lt;28kg, F:&amp;lt;18kg) and slow VEL (&amp;lt;1.0m/sec) was higher in DM subjects than non-DM subjects (DM vs non-DM, low HSG: 18.3% vs 5.6% in men, 28.0% vs 17.3% in women, slow VEL: 40.6% vs 30.7% in men, 61.7% vs 46.2% in women). After adjusting for age and BMI, men with DM had lower muscle mass (ASM, ASM/height2,), TMA and NAMA index but higher LAMA index and IMAT index compared to men without DM. Also, men with DM had lower HGS (p=0.001) and poor STST (p=0.008) than men without DM. In women, muscle mass and muscle quality indices were not significantly different with or without DM, but women with DM had worse STST than women without DM (p=0.013). Age and sex adjusted HSG, but not VEL and STST, was positively associated with muscle mass (ASM, ASM/height2, ASM/BMI, and TMM). Age and sex adjusted HSG, VEL, and STST were positively associated with NAMA index and negatively associated with LAMA index and IMAT index regardless of DM. Linear regression analysis revealed that both ASM and NAMA (or LAMA) indices were independent association factors for HGS. Subjects with DM showed a more pronounced decrease in physical performance and muscle strength than a decrease in muscle mass. In this population-based cohort, less myosteatosis was associated with greater muscle strength and better physical performance, regardless of muscle mass or DM status. Presentation: 6/2/2024

8413 Skeletal Muscle Mass, Insulin Sensitivity, And Beta-Cell Function In The Development Of Type 2 Diabetes: A 16-Year Prospective Cohort Study

Abstract Disclosure: H. Mun: None. S. Lee: None. S. Kim: None. S. Yoo: None. J. Son: None. Background: The relationship of relative muscle mass with beta-cell dysfunction and insulin resistance in the development of type 2 diabetes is unclear. We therefore aimed to evaluate longitudinal changes in glycemia, insulin sensitivity, and beta-cell function according to muscle mass. Methods: We prospectively evaluated 7090 middle-aged and older participants without diabetes at baseline every 2 years with oral glucose tolerance tests for 16 years in the Korean Genome Epidemiology Study. Weight-adjusted appendicular skeletal muscle mass was used to derive the muscle mass index (MMI). Using linear mixed-effect models, we assessed trajectories of fasting and 2-hour post-load glucose (2hPG), the composite insulin sensitivity index (ISIcomp), the 60-minute insulinogenic index (IGI60), and the disposition index (DI) according to sex-specific MMI tertiles before diagnosis with type 2 diabetes or the completion of follow-up. Results: During a median follow-up of 13.9 years, 1742 (24.5%) participants were diagnosed with type 2 diabetes. The risk of developing type 2 diabetes gradually increased as MMI decreased (multivariable-adjusted hazard ratio 1.36; 95% CI 1.29; 1.44 per SD decline in MMI). After age- and sex adjustment, significant differences were found in fasting and 2hPG trajectories between low and high MMI tertiles during follow-up (p &amp;lt; 0.001 for group-by-time interaction). The low MMI tertile showed significantly lower ISIcomp and DI at baseline compared to the high MMI tertile. The rate of increase in IGI60 was significantly lower in the low MMI tertile than in the high MMI tertile (0.0021 vs. 0.0191; p &amp;lt; 0.001) despite a progressive decline in ISIcomp during follow-up. The rate of decrease in DI was significantly greater in the low MMI tertile than in the high MMI tertile (-0.0228 vs. -0.006; p &amp;lt; 0.001). Conclusion: Sufficient muscle mass in middle-aged and older adults could protect against incident type 2 diabetes by preserving beta-cell function to compensate for aging-induced reductions in insulin action, independent of obesity. Presentation: 6/1/2024

8127 HOMA-IR Predicts Muscle Wasting During Androgen Deprivation Therapy

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None. Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p&amp;lt;0.001, n=49), fat mass (r=0.55, p&amp;lt;0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p&amp;lt;0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p&amp;lt;0.001, n=46), delta lean mass (r=-0.58, p&amp;lt;0.001, n=46), delta ASMI (r=-0.52, p&amp;lt;0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR. Presentation: 6/3/2024

8127 HOMA-IR Predicts Muscle Wasting during Androgen Deprivation Therapy

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None. Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p&amp;lt;0.001, n=49), fat mass (r=0.55, p&amp;lt;0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p&amp;lt;0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p&amp;lt;0.001, n=46), delta lean mass (r=-0.58, p&amp;lt;0.001, n=46), delta ASMI (r=-0.52, p&amp;lt;0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR. Presentation: 6/3/2024

9215 Role Of Insulin/IGF1 Signaling And FoxO Transcription Factors In Satellite Cell And Skeletal Muscle Development And Senescence

Abstract Disclosure: Y. Yu: None. G. Wang: None. B.T. O'Neill: None. C.R. Kahn: None. Aging is associated with loss of skeletal muscle mass, deficiency of satellite cell (SC) function, and increase in intramuscular adipose tissue (IMAT) and insulin resistance posing threats to health and quality of elder life. Insulin / IGF1 signaling and their downstream signaling pathways play crucial roles in muscle function, as well as longevity a broad range of species. To identify the role of Insulin / IGF1 signaling in skeletal muscle homeostasis and aging/senescence, we took advantage of Cre-loxp mouse model using Pax7-Cre or HAS-Cre mice cross with insulin receptor (IR) and IGF1 receptor (IGF1R) double flox mice to create IR/IGF1R double knockout mice in both muscle progenitors (satellite cells) and mature skeletal muscle cells. We refer to the PaxCreIRIGF1RKO as the P7DKO and HSACreIRIGF1RKO as simply the DKO. Both P7DKO and DKO mice show severe loss of skeletal muscle with increased markers of cellular senescence and increased IMAT infiltration. This was indicated by a 60% loss of muscle mass, morphological evidence of skeletal muscle with atrophy and increased adipocyte infiltration, with a &amp;gt;6-fold increase of adipocyte marker Perlipin1. The muscle also exhibited 2- to 10-fold increases of cellular senescence and senescence-associated secretory markers, including Cdkn1a, Cdkn2a, Trp53, CD68, Cxcl14, and Ccr2. Both the whole skeletal muscle and primary satellite cells isolated from P7DKO mouse muscle show a higher level of senescence-associated beta-galactosidase, as compared to the cells from littermate controls. This was accompanied by a deficiency of proliferation and differentiation of the satellite cells. Interestingly, simultaneous knockout of Foxo1/3/4 in the DKO mouse muscle rescued the muscle atrophy, reduced IMAT infiltration and reduced skeletal muscle cell senescence. Thus, insulin/IGF1 signaling in satellite cells and mature muscle cells plays not only an important role in skeletal muscle development, but also skeletal muscle cell senescence, and this is mediated, in large part, through FOXO transcription factors. This pathway and these proteins provide both new insights and potential targets for improving skeletal muscle homeostasis and function in the elderly. Presentation: 6/2/2024

7551 Association of Remnant Cholesterol with Sarcopenia in Korean Adults: A Nationwide Population-Based Study using Data from the KNHANES

Abstract Disclosure: S. Jang: None. S. Hwang: None. A. Jang: None. K. Kim: None. J. Yu: None. N. Kim: None. H. Yoo: None. J. Seo: None. S. Kim: None. N. Kim: None. S. Baik: None. K. Choi: None. Objectives: Mounting evidences indicate the importance of interplay between skeletal muscle and lipid metabolism. Remnant cholesterol (remnant-C) is considered as one of the principal residual risk factors for atherosclerotic cardiovascular disease (ASCVD) as well as metabolic disorders, but there is limited study about the impact of remnant-C on sarcopenia. Research design and Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 was used in this nationwide population-based study. A total of 17,408 participants were enrolled. Subjects were categorized into 4 groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry (DXA). Results: 1,989 participants (11.4%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.8%; Q2, 9.9%; Q3, 12.9%; Q4, 17.1%). In the full adjusted model, those in the highest remnant-C quartile group showed the highest odds ratio for low muscle mass after adjusting for various confounding factors (Q2, 1.18 [0.95-1.47]; Q3, 1.12 [0.9-1.39]; Q4, 1.37 [1.1-1.71], P &amp;lt;0.05). A wide range of subgroup and sensitivity analyses showed consistent results, which may support the robustness of the present findings. Conclusions: Increased remnant-C value is related to high risk of low muscle mass in Korean population. Remnant-C may be a novel marker to predict and manage sarcopenia in the aging society. There should be future research to verify its clinical usefulness. Presentation: 6/2/2024

8553 GDF-15 Levels In Patients With Prostate Cancer On Androgen Deprivation Therapy

Abstract Disclosure: S.D. Jaramillo-Quiroz: Other; Self; VAPSHCS: Director Fund Research Fellowship/UW Abrass Family Fellowship Fund. CDMRP (PC170059).. L. Caeiro: None. L.J. Anderson: None. J.M. Garcia: None. Growth Differentiation Factor 15 (GDF-15) is a stress-induced cytokine known to induce anorexia and cachexia and a biomarker of biological aging, mitochondrial dysfunction, and worse hand grip strength and poor survival in different settings. Also, GDF-15 has pleiotropic functions at all stages of tumorigenicity and is suggested as a marker to differentiate BPH from PCa. Androgen Deprivation Therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), but it also decreases muscle mass and function and Quality of life (QOL). The role and effects of GDF-15 in prostate cancer patients undergoing ADT are not well characterized and was explored in this longitudinal, 6-month, observational study that recruited men with (PCa) starting ADT (n=60, mean age 69). Body composition [dual energy X-ray absorptiometry (DEXA), body weight history], physical performance [handgrip strength (HGS), 6-minute walk test (6MWT), energy expenditure (indirect calorimetry and actigraphy)], were assessed before, at 3 and 6 months after starting ADT. QoL was assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). GDF-15 was measured by ELISA. Mean differences performed with standard error of the mean, repeated measures ANOVA and Tukey’s Post Hoc test. Correlations were assessed by Spearman’s. After 6 months of ADT, fat mass was increased (mean difference: 1.14 ±0.38, p=0.0029), and lean muscle mass (mean difference: -1.214 ± 0.38, p=0.005), appendicular lean mass (ALM, mean difference: -0.879 ± 0.19, p=&amp;lt;0.0001). HGS (mean difference: -2.927 ± 0.59, p=&amp;lt;0.0001), and VO2 max decreased (mean difference -3.31 ± 0.83, p=0.0007). Baseline GDF-15 (mean 1456.59 ± 1022.80) was correlated with the changes in weight (r: -0.38, p=0.01), BMI (r: -0.33, p=0.01), ALM (r: -0.29, p=0.04), and fatigue (r: -0.38, p=0.004). As shown, baseline GDF-15 was inversely correlated with changes in weight, appendicular lean mass, and fatigue in subjects undergoing ADT, highlighting the possibility of its role as a biomarker and therapeutic target of body composition and patient-reported outcomes in this setting. Presentation: 6/1/2024

8381 The Pro-atrophic Effect of Vitamin D Binding Protein in Skeletal Muscle and Its Involvement in Cancer-Induced Muscle Wasting

Abstract Disclosure: N. Filigheddu: None. T. Raiteri: None. S. Reano: None. A. Scircoli: None. A. Antonioli: None. F. Prodam: None. Vitamin D binding protein (VDBP), encoded by the Gc gene, is a multifunctional serum glycoprotein synthesized by hepatocytes, whose primary function is the transport of vitamin D metabolites in the bloodstream. In addition, VDBP enhances the chemotactic activity of neutrophil chemoattractants and takes part in the actin-scavenger system by acting as a monomeric G-actin-binding protein. Several studies have reported a correlation between increased levels of VDBP and various pathologies often associated with muscle wasting, including different types of tumors. Given these findings, we hypothesized that VDBP may play a role in skeletal muscle homeostasis.In vitro, treatment of C2C12 myotubes with 100 mM VDBP for 24 h induced the perturbation of intracellular actin dynamics due to VDBP's ability to bind G-actin that, in turn, led to mitochondrial dysfunction (i.e., mitochondrial membrane potential dissipation, respiratory impairment, increased ROS production, induction of the fission machinery), exacerbation of autophagy, and, eventually, atrophy, seen as the reduction of myotube diameter. Remarkably, pharmacological intervention on myotubes with jasplakinolide (250 mM, 30 min pre-treatment) to counteract VDBP effects on intracellular actin dynamics was sufficient to prevent VDBP-induced atrophy. To assess if VDBP had a causative role in muscle atrophy in vivo, we injected VDBP (1.5 mg/Kg) every 48 h for one week in the tibialis anterior muscles of Gc knock-out mice (VDBP KO). At the end of the experimental period, we observed the induction of the mitophagic gene Bnip3, impairment of muscle performances (26% reduction of grip strength at the endpoint), and a 16% reduction of muscle mass compared to the saline-injected contralateral muscles, confirming the atrophic effect of VDBP in vivo.Coherently with the upregulation of VDBP observed in cancer patients, VDBP levels also increase in murine models of cancer cachexia. To test the hypothesis that VDBP could play a role in cancer-associated muscle wasting, we induced cancer cachexia in VDBP KO mice by inoculating 106 Lewis Lung Carcinoma (LLC) cells resuspended in 100 μl of saline on the back of mice. Tumor-bearing VDBP KO mice preserved their body weight and performances, and the muscle loss was lessened by more than 50% compared to cachectic WT mice. Notably, between the two groups, there were no differences in tumor growth or food intake, ruling out the possibility that the reduction in muscle wasting could depend on smaller tumors or differential development of anorexia in the two genotypes. In conclusion, we demonstrated that VDBP acts as a hormone per se, having a direct pro-atrophic activity on skeletal muscle. Our data suggest that VDBP could represent a potential therapeutic target to treat cancer cachexia and other pathologies in which the rise of VDBP could impinge muscle mass and functionality. Presentation: 6/1/2024

12583 Nutrient Intake And Physical Performance In Patients With Acromegaly

Abstract Disclosure: N.N. Hupalowski: None. C.P. Rocha: None. S.Z. Fidalski: None. C.L. Boguszewski: Consulting Fee; Self; Recordati. Research Investigator; Self; Crinetics. Speaker; Self; Ipsen, Novo Nordisk. V.Z. Borba: None. Acromegaly is a chronic disease characterized by increased levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). These patients exhibit increased skeletal muscle mass but poorer performance in functional physical assessments. Certain nutrients are important for both muscle mass and strength, as well as for maintaining an anti-inflammatory state in the body. Objective: To assess the correlation between nutrient intake and physical performance in patients with acromegaly. Patients and Methods: An observational, cross-sectional study of patients with acromegaly matched 1:1 by sex and age with a control group. Patients underwent analysis of dietary patterns using the validated Food Frequency Questionnaire (FFQ), and physical performance and strength were measured using Hand Grip Strength (HGS), 5 Times Seat to Stand Test (STST), Time Up and Go (TUG), and Short Physical Performance Battery (SPPB) tests. Results: It was evaluated 47 patients (54.1% women; mean age 56.3 ± 11.6 years), which were compared with 36 controls (53.9% women; mean age 56.7 ± 13.4). There was no difference between groups in HGS evaluation. The performance of patients with acromegaly were poorer in the STST, SPPB and TUG. Better performance was associated with selenium (p=0.045), vitamin E (p=0.034), flavonol (p=0.02) and vitamin A (0.024) intake. Conclusion: Physical performance is compromised in patients with acromegaly, especially in lower limbs, and it was associated with lower consumption of selenium, vitamin E, flavonol and vitamin A. Presentation: 6/2/2024

12271 Differential Impacts Of Body Composition Indices On Cortisol Response And Hpa Axis Activity

Abstract Disclosure: S.G. Gonsalves: None. A. Ross: None. M.E. Steele: None. L.N. Saligan: None. Aim: The continued interest in the influence of muscle mass and fat distribution on stress stems from its implications on preventative healthcare. Fat mass index (FMI) and fat-free mass index (FFMI) were proposed as valuable indicators of body composition beyond body mass index (BMI). This study investigated correlations of FMI and FFMI with inflammatory stress markers, hypothesizing that these body composition indices identify inflammatory stress markers more distinctly than BMI. Methods: Skeletal muscle mass was assessed by Dual-Energy X-ray Absorptiometry, HPA axis response through an adrenocorticotropic hormone (ACTH) stimulation test, and markers of inflammation and stress response (e.g., dehydroepiandrosterone, DHEA) from peripheral blood of 104 healthy individuals aged 18-71 years, 52% female, with a mean BMI of 26.3 (+4.83). Perceived stress and fatigue were captured using patient-reported outcome questionnaires before the HPA procedure. Results: ACTH correlated with FFMI at baseline (ρ=0.299, p=0.009) and 60 minutes (ρ=0.254, p=0.041). Cortisol correlated with FFMI at 15 (ρ=–0.248, p≤0.025), 30 (ρ=–0.284, p≤0.010), and 60 minutes (ρ=–0.364, p≤0.001), and with BMI at 15 (ρ=–0.228, p=0.041). FMI and BMI did not correlate with ACTH and FMI with cortisol at any timepoint. With repeated measures ANOVA, FFMI at 50th percentile had large effect on cortisol (p=0.005, partial eta=0.094) at each timepoint, higher for the under lean than those with higher FFMI, compared to BMI at the same percentile (p=0.037, partial eta=0.054). None of the indices reached significance with ACTH. FMI correlated with Erythrocyte Sedimentation Rate (ESR) (ρ=0.521), C-reactive protein (CRP, ρ=0.493, both at p≤0.001), DHEA (ρ=0.252, p=0.030), and epinephrine (ρ=–0.246, p=0.045). FFMI was not correlated with ESR and CRP. BMI correlated only with albumin (ρ = –0.412, p ≤ 0.001 and CRP (ρ=0.342, p≤0.003). Discussion: The higher correlations of inflammatory stress markers with FMI and FFMI, as compared to BMI, supports our study hypothesis. These results hint that these body composition indices may detect subtle stress-related inflammatory changes than BMI. Future research should clarify underlying mechanisms driving these associations and explore the impact of targeted interventions on these indices and subsequent changes to inflammation and stress. Presentation: 6/1/2024

9268 The Pro-atrophic Effect of Vitamin D Binding Protein in Skeletal Muscle and Its Involvement in Cancer-Induced Muscle Wasting

Abstract Disclosure: N. Filigheddu: None. T. Raiteri: None. S. Reano: None. A. Scircoli: None. A. Antonioli: None. F. Prodam: None. Vitamin D binding protein (VDBP), encoded by the Gc gene, is a multifunctional serum glycoprotein synthesized by hepatocytes, whose primary function is the transport of vitamin D metabolites in the bloodstream. In addition, VDBP enhances the chemotactic activity of neutrophil chemoattractants and takes part in the actin-scavenger system by acting as a monomeric G-actin-binding protein. Several studies have reported a correlation between increased levels of VDBP and various pathologies often associated with muscle wasting, including different types of tumors. Given these findings, we hypothesized that VDBP may play a role in skeletal muscle homeostasis.In vitro, treatment of C2C12 myotubes with 100 mM VDBP for 24 h induced the perturbation of intracellular actin dynamics due to VDBP's ability to bind G-actin that, in turn, led to mitochondrial dysfunction (i.e., mitochondrial membrane potential dissipation, respiratory impairment, increased ROS production, induction of the fission machinery), exacerbation of autophagy, and, eventually, atrophy, seen as the reduction of myotube diameter. Remarkably, pharmacological intervention on myotubes with jasplakinolide (250 mM, 30 min pre-treatment) to counteract VDBP effects on intracellular actin dynamics was sufficient to prevent VDBP-induced atrophy. To assess if VDBP had a causative role in muscle atrophy in vivo, we injected VDBP (1.5 mg/Kg) every 48 h for one week in the tibialis anterior muscles of Gc knock-out mice (VDBP KO). At the end of the experimental period, we observed the induction of the mitophagic gene Bnip3, impairment of muscle performances (26% reduction of grip strength at the endpoint), and a 16% reduction of muscle mass compared to the saline-injected contralateral muscles, confirming the atrophic effect of VDBP in vivo.Coherently with the upregulation of VDBP observed in cancer patients, VDBP levels also increase in murine models of cancer cachexia. To test the hypothesis that VDBP could play a role in cancer-associated muscle wasting, we induced cancer cachexia in VDBP KO mice by inoculating 106 Lewis Lung Carcinoma (LLC) cells resuspended in 100 μl of saline on the back of mice. Tumor-bearing VDBP KO mice preserved their body weight and performances, and the muscle loss was lessened by more than 50% compared to cachectic WT mice. Notably, between the two groups, there were no differences in tumor growth or food intake, ruling out the possibility that the reduction in muscle wasting could depend on smaller tumors or differential development of anorexia in the two genotypes. In conclusion, we demonstrated that VDBP acts as a hormone per se, having a direct pro-atrophic activity on skeletal muscle. Our data suggest that VDBP could represent a potential therapeutic target to treat cancer cachexia and other pathologies in which the rise of VDBP could impinge muscle mass and functionality. Presentation: 6/1/2024

9179 Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting

Abstract Disclosure: M.O. Conn: None. D.M. Marko: None. J.D. Schertzer: None. Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting Diabetes is characterized by elevated blood glucose resulting from defective insulin secretion and/or insulin resistance. Intermittent fasting, a popular weight loss strategy involving periodic reduction of caloric intake, can improve glycemia. Fasting shifts metabolism from carbohydrates to free fatty acids and ketones. However, high blood insulin can inhibit lipolysis and alter metabolic substrate selection in prediabetes, resulting in muscle catabolism to maintain energy homeostasis. Clinical studies have observed a significant decrease in muscle mass in subjects with obesity and diabetes. Our research aims to characterize lean mass versus fat loss after intermittent fasting in a mouse model of obesity and type 2 diabetes (T2D) and investigate the role of muscle alanine catabolism. We hypothesized that intermittent fasting would promote less lipolysis and more muscle alanine catabolism, causing more muscle loss in diabetic mice than controls. We compared male db/db mice manifesting obesity, hyperglycemia, and hyperinsulinemia to age-matched db/+ (control) mice. Our lab established a 5:2 repeated fasting protocol of ad-libitum access to food for 5 days a week and 2 days of fasting on non-consecutive days. Blood glucose was monitored weekly in fed and fasted states to assess glycemic control. While intermittent fasting lowered fasted blood glucose in both groups, no significant body weight or metabolic tissue mass changes were observed. Metabolic cage data demonstrated increased reliance on fat-based substrates for energy in control mice that underwent intermittent fasting during feeding and fasting periods. Diabetic mice did not show significant changes in the fasted state, but intermittent fasting led to increased reliance on carbohydrate oxidation during re-feeding periods, indicating impaired metabolic flexibility. After 10 weeks, the mice were sacrificed, and metabolic tissue histology (adipose, liver, skeletal muscle) will be performed. We will also analyze serum markers (alanine, fatty acids, glycerol, glucose, insulin) and the activity of the metabolic enzyme alanine transaminase (ALT) in the muscle and liver. This experiment will improve our understanding of how lipolysis and protein breakdown in muscle regulate lean mass versus fat mass loss in obesity and T2D, leading to more effective tailoring of fasting to specific populations. Presentation: 6/3/2024