Decreased Muscle Mass Research Articles

GABA Prevents Sarcopenia by Regulation of Muscle Protein Degradation and Inflammaging in 23‐ to 25‐Month‐Old Female Mice

ABSTRACTBackgroundSarcopenia is the gradual decrease in skeletal muscle mass, strength and function in elderly individuals. Gamma‐aminobutyric acid (GABA) is a neurotransmitter naturally produced from glutamate by the enzyme glutamic acid decarboxylase. Age‐related decline in GABA is linked to age‐related motor and sensory decline and seems to affect sarcopenia, yet no detailed study has been conducted. In this study, we aimed to investigate the effect of GABA on improving sarcopenia by suppressing muscle protein degradation through supplementing decreased GABA in old mice.MethodsGABA (10 or 30 mg/kg/day) was orally administered daily to young (3 months) and old (21–23 months) C57BL/6 mice for 7 weeks. The body weight and grip strength of the mice were measured weekly at the same time. After sacrificing the mice, the quadriceps and gastrocnemius muscles were excised from their hind limbs, and the spleen and serum were collected. Histological, biochemical and molecular analyses were conducted in various experiments.ResultsThe administration of GABA increased muscle strength (+41%, +70% compared to the aged mouse control group, GABA at doses of 10 or 30 mg/kg/day respectively, p < 0.05) and muscle mass (quadriceps: +28%, +46%; gastrocnemius: +12%, +19%, p < 0.05) in old mice. This increase was accompanied by a cross‐sectional area (CSA) increase in the quadriceps and gastrocnemius muscle (p < 0.05). The administration of GABA increased IGF‐1 levels in serum (p < 0.05), leading to the activation of muscle protein synthesis. We found that GABA inhibits sarcopenia by regulating muscle protein degradation through the activation of Akt/mTOR/FoxO3a signalling pathways. GABA also regulates inflammaging, which is a hallmark of age‐related muscle atrophy. There was a significant increase in the F4/80 + CD11b + total macrophage ratio in gastrocnemius and spleen, especially the M1 macrophage ratio increased in old mice. However, GABA administration was effective in suppressing M1 macrophages (gastrocnemius: −40%, − 53%; spleen: −22%, −26%, p < 0.05). Pro‐inflammatory cytokines such as TNF‐α and IL‐6, primarily secreted by M1 macrophages, are also decreased by treatment with GABA (TNF‐α: −24%, −27%; IL‐6: −45%, −59%, p < 0.05).ConclusionsTogether, this study demonstrates the importance of GABA in maintaining muscle and low‐chronic inflammation during ageing. We suggest that GABA shows potential as a substance that can effectively address sarcopenia and enhance the overall lifespan and well‐being of older individuals.

Biometric Changes Up to 2 Years After Hip Arthroscopy in National Collegiate Athletic Association Division I Athletes.

Patients who undergo hip arthroscopy for femoroacetabular impingement (FAI) require lower extremity immobilization for an extended period of time. Periods of immobilization combined with surgery have been associated with decreased muscle mass and bone mineral density (BMD). The purpose of this study was to characterize postoperative body composition and BMD changes after arthroscopy for FAI. It was hypothesized that both lean mass and BMD would decrease postoperatively and then normalize over time. Case series; Level of evidence, 4. This was a retrospective review of 23 National Collegiate Athletic Association Division I athletes who underwent hip arthroscopy between 2017 and 2019 and had a dual-energy x-ray absorptiometry scan preoperatively and at 3, 6, 12, or 24 months postoperatively. Linear mixed-effects models were used to compare pre- with postoperative lean and fat mass values for the total body and total leg (both operative and nonoperative sides) as well as trunk, pelvic, and spinal BMD. For total-leg, femur, and femoral BMD, linear mixed-effects models were used to evaluate the influence of time, side (operative vs nonoperative), and their interaction on each outcome measure. Regarding pelvic BMD, compared with baseline (mean, 1.41 g/cm2 [95% CI, 1.33-1.49]), significant decreases were seen at postoperative 3 months (mean, 1.36 g/cm2 [95% CI, 1.28-1.45 g/cm2]; P < .001) and 6 months (mean, 1.39 g/cm2 [95% CI, 1.27-1.52 g/cm2]; P < .01) but not at 12 months (mean, 1.42 g/cm2 [95% CI, 1.33-1.51 g/cm2]; P = .319). Total-leg BMD for the operative side increased significantly from baseline (mean, 1.52 g/cm2 [95% CI, 1.43-1.61 g/cm2]) to ≥2 years postoperatively (mean, 1.56 g/cm2 [95% CI, 1.47-1.65 g/cm2]) (P = .005). Combined leg fat mass was increased from baseline (mean, 6427 g [95% CI, 4855-7999 g]) to ≥2 years (mean, 11645 g [95% CI, 7845-15,446 g]) (P < .01). There were no significant differences in total-body fat or lean mass or combined-leg lean mass. In this patient population, a postoperative decrease in pelvic BMD that resolved by 12 months and an increase in total-leg BMD on the operative side at ≥2 years were observed. While hip arthroscopy for FAI may have significant benefits for long-term body composition and bone mass, clinicians should be aware of the potential implications of decreased bone mass for up to 12 months postoperatively.

Sex-Specific Association of Low Muscle Mass with Depression Status in Asymptomatic Adults: A Population-Based Study

Background: The objective of this study was to examine the correlation between low muscle mass (LMM) and depression, with a specific focus on identifying the sex-specific relationship between LMM and depression in a large sample. Methods: This population-based cross-sectional study involved 292,922 community-dwelling adults from 2012 to 2019. Measurements were taken using the Center for Epidemiological Studies Depression (CESD) scale and body composition analyses. Depression was defined as a CESD score ≥ 16, and severe depression as a CESD score ≥ 22. LMM was defined as an appendicular muscle mass/height2 below 7.0 kg/m2 in men and below 5.4 kg/m2 in women. Sex-based multivariable logistic regression analyzed the LMM–depression association, adjusting for confounders, with depression status and severe depression status as dependent variables. Results: Both men and women in the LMM group had an increased odds of depression (men, adjusted odds ratio = 1.13 [95% confidence interval = 1.03–1.12]; women, 1.07 [1.03–1.23]) and severe depression (men, 1.20 [1.05–1.36]; women, 1.10 [1.04–1.15]) compared to those in the control group. Men showed a stronger association between LMM and the presence of depression (p for interaction = 0.025) and the presence of severe depression (p for interaction = 0.025) compared to women. Conclusions: Decreased muscle mass was independently associated with increased chances of depression and severe depression in both sexes, with a significantly stronger association in men compared to women. This highlights the potential significance of LMM as a predictor of depression, particularly in men.

The Effect Combined Of Intradialytic Exercise: Static Stretching And Dynamic Streching Lower Limb, Increase Physical Funtion In Chronic Kidney Diseases On Haemodialysis Patients Quasi Experiment

Background: Individuals with end-stage kidney disease (ESKD) usually engage in minimal physical activity, as renal failure progresses in chronic kidney disease (CKD), muscle mass and physical function decrease. Physical activity (PA) is important in maintaining/improving health in all population. Aim of this study to evaluate effect exercise of combine static stretching and dynamic stretching increasing Physical Function in CKD on HD patients. Methods: design of this study was quasi experiment in one group 39 respondents CKD on HD patients meet inclusion criteria. Implementation 12 weeks intradialytic exercise combine static and dynamic stretching lower limbs include leg, ankles, knee, femoral and hip. During exercise evaluate using Borg Skill to know level of fatigue. Comparing with before-after test Time Up and Go 3 meters return measurement. Result: The results of this study demonstrate that the mean values of functional balance, which are much lower in this population than in their healthy counterparts, can be improved by a video-based intradialytic exercise program that includes stretching and endurance activities. In particular, notable advancements were noted in the average TUG test 3 meter return result, which is a reliable indicator of hospitalization, cardiovascular events, and mortality in dialysis patients. Conclusion all participants reported after 12 weeks static and dynamic stretching felt more flexible range of motion knee and leg, walking stronger than before and felt more conformable in walking reported, significant different before and after given static and dynamic stretching, both Static and dynamic stretching effective for improving functional balance and physical performance, Recommended static and dynamic stretching to be rutine activity in Hemodialysis unit.

Effect of Fontan circulation on body composition and correlation with exercise capacity

Abstract Background There is growing attention to body composition in Fontan patients (FP) and preliminary results suggest that FP have an increased fat mass and a decreased muscle mass compared to the healthy population. FP also have reduced exercise capacity compared to health peers. However, data are still limited. Purpose The aim of our study was to compare the body composition (BC) of adult patients with Fontan circulation and healthy controls and to assess the correlation with functional capacity. Material and Methods Case control study on adult patients with Fontan circulation (FP) and age and gender matched healthy controls (HC). The following characteristics were recorded: age, gender, morphology of the systemic ventricle, type of Fontan circulation, level of physical activity (PAR, 0-7 points, 0 = sedentary - 7 = running &amp;gt; 3hours/week). S-score muscle, T-score bone, fat mass (FM%), intra-muscular adipose tissue (IMAT), abdominal adipose tissue (AAT), intracellular water (ICW), extracellular water (ECW), total body water (TBW), were measured through multi-frequency bioelectrical impedance technology in the FP and in the HC. Correlation was made for FP between body composition and oxygen consumption at peak exercise (VO2 peak), VE/VCO2 slope and NYHA class as indicator of functional capacity. Results Thirty Fontan patients (FP, mean age 24±6 yrs, 70% males) and 30 matched healthy controls (HC) were recruited in the study. The systemic ventricle was dominant left in 14 patients (47%), dominant right in 16 (53%). Four patients had atrio-pulmonary connection, the remaining were palliated with a lateral tunnel (n=26, 87%). The analysed parameters are summarised in Table 1. PAR was reduced in FP compared to HC (median 4.0 points in FP versus 7.0 points in HC, p 0.024). There was no difference in the BMI, fat mass, and body water between FP and HC. However, FP showed significantly lower S and T scores compared to the HC (S-score: -0,75 in FP versus 0,0 in HC, p 0.003. T-score: -0.9 in FP versus -0.25 in HC, p 0.001). In FP, NYHA Class was I in 28 patients (93%), II in 1 (3,5%) and III in 1 (3.5%) patient. The mean VO2 was 23.4±5.4mlO2/kg/min and mean VE/VCO2 slope 32±7. There was a direct correlation between VO2 peak and the PAR (rho 0.443, p 0.044). No correlation was found between the VO2 peak, the VE/VCO2 slope or the NYHA Class and the analysed parameters of body composition. Conclusion FP have reduced muscle mass, and bone density compared to HC. In addition to the known reduced efficiency of the cardiac pump during exercise in FP, the lower level of conditioning contributes to the reduced exercise capacity in this population. Programs aiming to encourage physical activity are key and should be part of patients’ care.

Effects of Atezolizumab plus Bevacizumab on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma

Introduction: Pharmacological treatment of unresectable hepatocellular carcinoma (uHCC) includes sorafenib and lenvatinib, a tyrosine kinase inhibitor, which are linked to low serum levels of carnitine and reduced skeletal muscle volume. Nowadays, atezolizumab plus bevacizumab (Atezo/Bev) combination therapy is recommended as the first-line treatment for patients with uHCC. However, the association with decreased muscle mass or cardiac function is unknown. Therefore, this study aimed to evaluate the effects of Atezo/Bev on skeletal muscle volume and cardiac function in patients with uHCC. Methods: This retrospective study included 55 adult Japanese patients with chronic liver diseases and uHCC treated with Atezo/Bev. Patients were divided into three groups according to age: middle, preold, and old. Serum levels of carnitine and cardiac function were measured before and after 3 weeks of treatment. The psoas muscle index (PMI) was measured before and after 6 weeks of treatment. Results: After treatment, the global longitudinal strain was significantly lower in the old group, whereas the PMI and ejection fraction were significantly lower in the preold and old groups. However, no significant difference in serum levels of total carnitine and those fractions with treatment in each group was found. Cardiac function decreased in the preold and old groups. Conclusion: When treating patients with uHCC by Atezo/Bev, caution should be taken in preold and old patients because they are vulnerable to decreased skeletal muscle mass and deterioration of cardiac function. Strength training and regular monitoring of cardiac function are encouraged in these groups.

Photobiomodulation and Physical Exercise Modulate of Cell Survival Proteins in the Skeletal Muscle of Rats with Heart Failure and Diabetes Mellitus.

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p-AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Nutrition and Physical Activity in Older Adults with CKD patients: Two Sides of the Same Coin.

Nutrition and physical activity are two major issues in the management of CKD patients who are often older, have comorbidities and are prone to malnutrition and physical inactivity, conditions that cause loss of quality of life and increase the risk of death. We performed a multidimensional assessment of nutritional status and of physical performance and activity in CKD patients on conservative therapy in order to assess the prevalence of sedentary behaviour and its relationship with body composition. 115 consecutive stable CKD patients aged 45-80 years were included in the study. They had no major skeletal, muscular or neurological disabilities. All patients underwent a multidimensional assessment of body composition, physical activity and exercise capacity. Sedentary patients, as defined by mean daily METs &lt; 1.5 were older and differed from non-sedentary patients in terms of body composition, exercise capacity and nutrient intake, even after adjusting for age. Average daily METs were positively associated with lean body mass, muscle strength, 6-MWT performance, but negatively associated with fat body mass, body mass index and waist circumference. In addition, a sedentary lifestyle may have negative effects on free fat mass, muscle strength and exercise capacity, and may increase fat body mass. Conversely, s decrease in muscle mass and/or an increase in fat mass may lead to a decrease in physical activity and exercise capacity. There is a clear association and potential interrelationship between nutritional aspects and exercise capacity in older adults with CKD: they are really the two sides of the same coin.

Prospective Intervention Strategies Between Skeletal Muscle Health and Mitochondrial Changes During Aging.

Sarcopenia is a geriatric condition characterized by a decrease in skeletal muscle mass and function, significantly impacting both quality of life and overall health. Mitochondria are the main sites of energy production within the cell, and also produce reactive oxygen species (ROS), which maintain mitochondrial homeostasis-mitophagy (clearing damaged mitochondria); mitochondrial dynamics, which involve fusion and fission to regulate mitochondrial morphology; mitochondrial biogenesis, which ensures the functionality and homeostasis of mitochondria. Sarcopenia is linked to mitochondrial dysfunction, suggesting that muscle mitochondrial function therapy should be investigated. Extrinsic therapies are extensively examined to identify new treatments for muscular illnesses including sarcopenia. Changes in muscle physiology and lifestyle interventions, such as pharmacological treatments and exercise, can modulate mitochondrial activity in older adults. This PubMed review encompasses the most significant mitophagy and sarcopenia research from the past five years. Animal models, cellular models, and human samples are well covered. The review will inform the development of novel mitochondria-targeted therapies aimed at combating age-related muscle atrophy.

Examining the Safety of Dorsogluteal and Ventrogluteal Sites for Intramuscular Injection in Older Adults.

Muscle, subcutaneous tissue and total tissue thicknesses are important factors in successful intramuscular injection. Muscle mass decreases and subcutaneous tissue increases with age. This may negatively affect the safety and effectiveness of intramuscular injection in older adults by increasing the risk of bone contact and subcutaneous drug administration. Intramuscular injection sites should be evaluated in this respect, but no previous study has evaluated the most appropriate sites for safe and effective intramuscular injection in older adults. This study aimed to examine the safety of dorsogluteal and ventrogluteal injection sites in older adults. This cross-sectional study included 171 older adults who presented to the radiology clinic of a hospital between November 2022 and February 2023. We collected the study data using a descriptive characteristics form and an ultrasonographic measurement form. To complete the descriptive characteristics form, we interviewed the participants and measured their waist circumference, hip circumference, weight and height. Muscle, subcutaneous tissue and total tissue thicknesses at the ventrogluteal and dorsogluteal sites were determined by ultrasonography. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. At the ventrogluteal and dorsogluteal sites, respectively, total tissue thicknesses were 59.43 ± 11.21 and 48.78 ± 9.68 mm, subcutaneous tissue thicknesses were 20.07 ± 6.64 and 22.97 ± 7.40 mm and muscle thicknesses were 40.13 ± 5.59 and 25.61 ± 4.30 mm. Tissue thicknesses at both sites differed according to sex, weight, hip circumference and waist circumference (p < 0.05). Although both sites were acceptable according to the tissue thickness thresholds for intramuscular injection given in the literature (subcutaneous tissue < 25 mm, total tissue > 35 mm), the ventrogluteal site was more advantageous in terms of greater muscle thickness and lower subcutaneous tissue thickness. The results of this study indicated that both the ventrogluteal and dorsogluteal sites are safe for intramuscular injections in older adults in terms of tissue thickness. However, the ventrogluteal site may be safer for older adults because of the lower risk of bone contact and subcutaneous injection. Further studies are needed on this subject. This study is important in terms of determining the safe and effective gluteal site for IM injection in older people aged 65 and over, preventing complications that may arise from site selection, and developing nursing policies that consider older people as a special group in the selection of IM injection sites.

Prognostic value of body composition measures in breast cancer patients treated with chemotherapy

Breast cancer remains a significant public health issue, often resulting in severe side effects such as neutropenia, highlighting the need for reliable predictors of clinical outcomes. This study aimed to evaluate the predictive value of body composition measures for mortality, recurrence, and chemotherapy-induced neutropenia in patients with breast cancer following surgery and chemotherapy. We retrospectively analyzed 85 breast cancer patients who underwent surgery and chemotherapy between 2006 and 2016. Body composition was assessed using computed tomography (CT) or positron emission tomography (PET) at diagnosis and three years and five years post-diagnosis. Metrics included skeletal muscle area (SMA), skeletal muscle index (SMI), subcutaneous adipose tissue area (SAT), and visceral adipose tissue area (VAT). Longitudinal analysis revealed a decrease in muscle mass (P < 0.001 for both SMA and SMI) and nonsignificant changes in fat mass (P = 0.449 for SAT and P = 0.798 for VAT). A lower SMI at diagnosis was significantly associated with increased mortality (P = 0.019) and a higher incidence of grade 4 neutropenia (P = 0.008). There was no significant association between SMI at diagnosis and recurrence (P = 0.691). No associations were found between body composition measurements during the follow-up period and the clinical outcomes. Lower skeletal muscle mass at diagnosis is strongly associated with higher mortality and chemotherapy-induced complications in patients with breast cancer, highlighting the potential of readily available imaging techniques as valuable predictors of clinical outcomes.

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.

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

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

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

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

Exposure to air pollution, genetic susceptibility, and prevalence of sarcopenia in the UK

BackgroundThe role of environmental factors, particularly air pollutants, in the prevalence of sarcopenia remains unclear. ObjectivesThis study explored the relationship between the prevalence of sarcopenia and prolonged exposure to air pollutants, and investigated potential interactions with genetic susceptibility and inflammation. MethodsData from 408,117 people at baseline and 35,060 participants in the longitudinal analysis in the UK Biobank were used in this prospective cohort study. Utilizing land use regression models, air pollutants (nitrogen dioxide (NO2), nitric oxides (NOx), and particulate matter with aerodynamic diameters of ≤2.5 μm (PM2.5) and ≤10 μm (PM10) were estimated and classified into quartiles. Alterations in body composition were among the secondary results. ResultsLastly, 3353 people (0.8 %) developed sarcopenia. Higher levels of air pollutants were linked to an increased prevalence of sarcopenia after controlling for confounding variables (highest vs lowest quartile: NOx, OR, 1.21 [95 % CI, 1.16–1.26]; NO2, OR, 1.22 [95 % CI, 1.16–1.27]; PM2.5, OR, 1.17 [95 % CI, 1.12–1.22]; PM10, OR, 1.15 [95 % CI, 1.10–1.20]; all P<.001). Longitudinal analysis revealed that air pollutants had adverse changes in body composition, including increased muscle fat infiltration and decreased muscle mass. At baseline, the probability of sarcopenia was strongly correlated with NOx, NO2, PM2.5, and PM10, and increased with elevated PRSBMI or CRP levels in subgroup analyses. ConclusionAir pollutants may contribute to accelerated muscle aging and highlight the importance of environmental factors in sarcopenia development.

Evaluating changes in body composition, bone mass, and metabolic profile in an animal model undergoing transfeminine hormone therapy and physical exercise

Background & AimsGender-affirming hormone therapy (GAHT) is essential for transgender individuals seeking body modifications. For transfeminine people assigned male at birth, GAHT typically involves a combination of antiandrogens and estrogens. Despite its importance, the scientific literature presents inconsistencies regarding the effects of these hormones on nutritional status, body composition, and biochemical markers. This study aims to evaluate the impact of estradiol enanthate and dihydroxyprogesterone acetophenide (E2EN/DHPA) hormonal treatment, in conjunction with resistive physical exercise, on body composition and metabolic profiles. MethodsTwenty-eight male rats were divided into three groups: MO (control group, n=8), receiving sesame oil vehicle; MH (n=11), receiving E2EN/DHPA; and MEH (n=9), receiving E2EN/DHPA along with physical exercise. The hormonal treatment was administered every ten days for two months, while the exercise regimen involved stair climbing with progressively increasing weights, performed five times weekly for seven weeks. Evaluated parameters included body mass index (BMI), body composition (fat and lean mass), bone mineral density (BMD), and lipid profile (triglycerides, HDL-C, LDL-C). ResultsThe rats that received E2EN/DHPA showed significant changes in body composition and BMI, regardless of exercise. The MH group had increased body fat, while both the MH and MEH groups had decreased bone area and mineral content. However, BMD remained the same across all groups. Elevated triglyceride levels were observed, and the MEH group also had reduced LDL-C levels. HDL-C levels did not show significant variation. ConclusionThe study's findings show similarities to changes seen in transfeminine individuals undergoing GAHT with estrogen and antiandrogens. These changes include decreased muscle mass, increased body fat, preserved bone mineral density, and elevated triglycerides. The study also found that resistance exercise positively impacted lipid profiles, particularly in reducing LDL-C. These results highlight the need for further research and comparative trials on hormone therapy regimens.

Nutritional Aspects of Spina Bifida Care: Optimizing Medical Management and Surgical Healing.

This review aims to highlight background of contributing factors for suboptimal nutrition in individuals with spina bifida and introduce strategies for amelioration. Recent studies demonstrate increased risk of metabolic syndrome by neurosegmental level, which is associated with truncal obesity and reduced mobility. From the neonatal intensive care stay, which may disrupt breast feeding and the developing microbiome of the gastrointestinal tract, to early childhood various insults may lead to suboptimal feeding practices, preferences and dietary intake. Family coping skills, financial stressors may lead to food insecurity and/or residence in an area with limited availability of fresh food. As children grow, weakness and challenging transfers may lead to more sedentary lifestyle and weight gain despite limited linear growth. Body habitus changes including atrophy of the lower extremities may lead to decreased muscle mass and reduced energy expenditure, with predisposition to truncal obesity and metabolic syndrome.