Changes In Lean Body Mass Research Articles

Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

Background:Rehabilitation after repair of the anterior cruciate ligament (ACL) is complicated by the loss of leg muscle mass and strength. Prior studies have shown that preoperative rehabilitation may improve muscle strength and postoperative outcomes. Testosterone supplementation may likewise counteract this muscle loss and potentially improve clinical outcomes.Purpose:The purpose was to investigate the effect of perioperative testosterone administration on lean mass after ACL reconstruction in men and to examine the effects of testosterone on leg strength and clinical outcome scores. It was hypothesized that testosterone would increase lean mass and leg strength and improve clinical outcome scores relative to placebo.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:Male patients (N = 13) scheduled for ACL reconstruction were randomized into 2 groups: testosterone and placebo. Participants in the testosterone group received 200 mg of intramuscular testosterone weekly for 8 weeks beginning 2 weeks before surgery. Participants in the placebo group received saline following the same schedule. Both groups participated in a standard rehabilitation protocol. The primary outcome was the change in total lean body mass at 6 and 12 weeks. Secondary outcomes were extensor muscle strength, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score.Results:There was an increase in lean mass of a mean 2.7 ± 1.7 kg at 6 weeks postoperatively in the testosterone group compared with a decrease of a mean 0.1 ± 1.5 kg in the placebo group (P = .01). Extensor muscle strength of the uninjured leg also increased more from baseline in the testosterone group (+20.8 ± 25.6 Nm) compared with the placebo group (–21.4 ± 36.7 Nm) at 12 weeks (P = .04). There were no significant between-group differences in injured leg strength or clinical outcome scores. There were no negative side effects of testosterone noted.Conclusion:Perioperative testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, suggesting that this treatment may help minimize the effects of muscle atrophy associated with ACL injuries and repair. This study was not powered to detect differences in strength or clinical outcome scores to assess the incidence of testosterone-related adverse events.Clinical Relevance:Supraphysiological testosterone supplementation may be a useful adjunct therapy for counteracting muscle atrophy after ACL reconstruction. Further investigation is necessary to determine the safety profile and effects of perioperative testosterone administration on leg strength and clinical outcomes after surgery.Registration:NCT01595581 (ClinicalTrials.gov).

Testosterone Supplementation Increases Lean Mass in Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial

Objectives:Surgical reconstruction of the anterior cruciate ligament (ACL) is essential for those who wish to resume athletic activity following ACL rupture. However, the trauma of surgical repair and post-operative immobility can exacerbate muscle loss and strength. This study investigated the effect of perioperative testosterone administration on lean mass recovery following ACL reconstruction in men. The effects of testosterone on leg strength and clinical outcome scores were also investigated. We hypothesized that testosterone would increase lean mass and leg strength, and improve clinical outcome scores 6 and 12 weeks after surgery to a greater degree than placebo.Methods:This was a randomized, controlled, double blinded clinical trial comparing testosterone and placebo for recovery from ACL repair. Thirteen male subjects scheduled for ACL reconstruction were randomized into two groups, testosterone (n=6) and placebo (n=7). Participants in the testosterone group received 200 mg of testosterone administration weekly for 8 weeks starting 2 weeks prior to surgery. Participants in the control group received a saline placebo intramuscularly following the same schedule. Both intervention groups underwent standard physical rehabilitation. The primary outcome was change in total lean body mass at 6 and 12 weeks, measured by whole-body dual-energy x-ray absorptiometry. Secondary outcomes were extensor muscle strength measured using a Cybex Dynamometer, and the Tegner Activity Score (TAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS).Results:Total testosterone levels in the blood increased from baseline to an average of 860 ± 254 ng/dL by 1 day prior to surgery and 746 ± 173 ng/dL at 6 weeks post-surgery for the testosterone group. The differences in serum testosterone levels between the placebo and testosterone groups at 1 day prior to surgery and 6 weeks post-surgery were both statistically significant (p<0.001). We found that testosterone increased lean mass by 2.8 ± 1.7 kg from baseline at 6 weeks following surgery, while the placebo group had a decrease in lean muscle mass of 0.1 ± 1.5 kg (p=0.01) (Figure 1). Extensor strength of the non-injured leg had a greater increase from baseline in the testosterone group (20.8 ± 25.6 Nm) than the placebo group (-21.4 ± 36.7 Nm) at 12 weeks (p=0.02). There were no significant differences in injured leg strength or clinical outcome scores throughout the study period.Conclusion:Despite a catabolic environment, acute testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, and strength of the non-injured leg 12 weeks after surgery, to a greater degree than placebo. These results suggest that testosterone may be a novel, useful adjunct to physical therapy for knee surgery rehabilitation by offsetting perioperative muscle loss from surgery and immobility. Larger studies are now necessary to elucidate the effects of perioperative testosterone administration on injured leg strength and clinical outcomes following surgery.

Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial

BackgroundHead and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects.MethodsAt the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional.DiscussionThis randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy.Trial registrationApproved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov (NCT02557529) September 11th 2015.

Design of a randomized trial to determine the optimum protein intake to preserve lean body mass and to optimize response to a promyogenic anabolic agent in older men with physical functional limitation

The dietary protein allowance for older men to maintain lean body mass and muscle strength and to accrue optimal anabolic responses to promyogenic stimuli is poorly characterized. The OPTIMEN trial was designed to assess in older men with moderate physical dysfunction and insufficient habitual protein intake (<recommended dietary allowance, RDA, 0.8g·kg−1·d−1) the efficacy of consuming diets containing 163% RDA (1.3g·kg−1·d−1) for protein, compared to RDA, to increase lean mass, muscle performance, and physical function. A second aim was to determine whether increasing protein intake to 1.3 versus 0.8g·kg−1·d−1 would augment anabolic responses to a promyogenic agent, testosterone.For this randomized, double-blind, placebo-controlled six-month intervention trial, 92 men, 65years or older, with Short Physical Performance Battery scores 3–10, and habitual protein intakes <RDA, were assigned to one of four groups: 100% RDA plus placebo intramuscular injections weekly; 100% RDA plus weekly intramuscular injections of 100mg testosterone enanthate; 163% RDA plus placebo injections; or 163% RDA plus testosterone injections. All participants received portion-controlled packaged meals and group-specific dietary supplements containing either mixtures of casein and whey or carbohydrate, with identical appearance. The primary outcome was change in lean body mass assessed using dual energy X-ray absorptiometry. Secondary outcomes included maximal voluntary strength and power in leg press and chest press exercises, 6-minute walking distance, stair climbing power, and self-reported physical function.Results of the OPTIMEN trial have important implications for dietary protein guidance and policy, and efficacy of promyogenic drugs.

The Impact of Dietary Protein or Amino Acid Supplementation on Muscle Mass and Strength in Elderly People: Individual Participant Data and Meta-Analysis of RCT's.

Increasing protein or amino acid intake has been promoted as a promising strategy to increase muscle mass and strength in elderly people, however, long-term intervention studies show inconsistent findings. Therefore, we aim to determine the impact of protein or amino acid supplementation compared to placebo on muscle mass and strength in older adults by combining the results from published trials in a meta-analysis and pooled individual participant data analysis. We searched Medline and Cochrane databases and performed a meta-analysis on eight available trials on the effect of protein or amino acid supplementation on muscle mass and strength in older adults. Furthermore, we pooled individual data of six of these randomized double-blind placebo-controlled trials. The main outcomes were change in lean body mass and change in muscle strength for both the meta-analysis and the pooled analysis. The meta-analysis of eight studies (n=557) showed no significant positive effects of protein or amino acid supplementation on lean body mass (mean difference: 0.014 kg: 95% CI -0.152; 0.18), leg press strength (mean difference: 2.26 kg: 95% CI -0.56; 5.08), leg extension strength (mean difference: 0.75 kg: 95% CI: -1.96, 3.47) or handgrip strength (mean difference: -0.002 kg: 95% CI -0.182; 0.179). Likewise, the pooled analysis showed no significant difference between protein and placebo treatment on lean body mass (n=412: p=0.78), leg press strength (n=121: p=0.50), leg extension strength (n=121: p=0.16) and handgrip strength (n=318: p=0.37). There is currently no evidence to suggest that protein or amino acid supplementation without concomitant nutritional or exercise interventions increases muscle mass or strength in predominantly healthy elderly people.

Lean body mass, muscle fibre size and muscle function in cancer patients during chemotherapy and 10 weeks exercise

AbstractBackgroundChemotherapy can reduce muscle mass in cancer patients but the potential of exercise to ameliorate this is understudied, particularly at the myocellular level. The primary purpose was to investigate changes in lean body mass (LBM) and secondly single fibre cross‐sectional area (CSA) in cancer patients during chemotherapy and in combination with 10 weeks of exercise.MethodsIn a single‐arm trial, patients adhered to chemotherapy for at least 4 weeks (control period) before 10 weeks of exercise adjunct to chemotherapy (exercise period). LBM (Dual Energy X‐ray Absorptiometry) and single fibre CSA (muscle biopsies) were assessed at baseline, pre‐ and post‐exercise. Muscle strength, functional performance and aerobic capacity were also assessed.ResultsTen patients were included, however only six patients completed the protocol. LBM changed over time (p=0.013), but no significant changes were observed between specific time points. Numerically, LBM decreased by 0.3 kg (p=0.41, 95% CI: ‐1.1;0.5) from 41.3–41.0kg, during the control period and increased by 0.7 kg (p=0.16, 95% CI: ‐0.6;2.0) from 40.4–41.1 kg during exercise. Muscle fibre CSA did not change significantly over time (p=0.13), but decreased numerically in the control period by 703 μm2 (p=0.20, 95% CI: ‐1877; 470) and increased by 846 μm2 (trend, p=0.08, 95% CI: ‐162; 1854) following exercise. Muscle strength and functional performance were unchanged during the control period but improved post‐exercise.ConclusionsDespite non‐significant changes in muscle mass (due to small sample size), this study adds novel information on LBM and myocellular changes in cancer patients during chemotherapy and concurrent exercise.

P1.06-003 Anamorelin in Cachectic Patients with Advanced NSCLC, a Post-Hoc Pooled Efficacy Data Analysis of Two Phase 3 Trials

Anorexia-cachexia is a multifactorial syndrome frequently experienced by patients with non-small cell lung cancer (NSCLC). It is characterized by decreased body weight (mainly due to muscle loss) and is associated with worsen morbidity, poor tolerance of chemotherapy and reduced survival. The randomized, double-blind ROMANA 1 and ROMANA 2 phase 3 trials in cachectic NSCLC patients, demonstrated that the ghrelin receptor agonist anamorelin was well tolerated, improved body weight, lean body mass (LBM), fat mass (FM) and anorexia/cachexia symptoms and concerns, with no difference in handgrip strength compared to placebo. Here we assessed pooled efficacy and numbers needed to treat (NNT) from ROMANA 1 and ROMANA 2 studies. Stage III/IV NSCLC patients with cachexia (≥5% weight loss during prior 6 months or BMI<20 kg/m2) were randomized (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. Endpoints included changes in LBM, FM, total body mass (TBM) and in self-reported anorexia/cachexia symptoms and concerns. We present the pooled efficacy data from a post-hoc analysis from both trials (anamorelin, N=552; placebo, N=277); treatment differences, 95% CI, NNT and nominal p values from baseline to end of study. At the end of study, compared with placebo, anamorelin-treated patients significantly increased body composition parameters (LBM, appendicular LBM, FM and TBM), and a greater proportion of patients showed improvements in these parameters (Table). The anamorelin group also significantly improved anorexia/cachexia symptoms and concerns, and compared to placebo, more patients in the anamorelin arm achieved the minimally important difference of 4 points. Anamorelin has anabolic activity while improving symptom burden in cachectic patients with NSCLC. A significantly greater proportion of patients increased lean mass, fat mass and improved anorexia/cachexia symptoms and concern score in the anamorelin arm versus the placebo arm, with favorable NNT.

Blunting of adaptive thermogenesis as a potential additional mechanism to promote weight loss after gastric bypass

BackgroundAdaptive thermogenesis (AT) is described as a change in resting metabolic rate (RMR) that is greater than would be predicted from changes in lean body mass (LBM) and fat mass (FM) alone during periods of energy imbalance. Whereas an AT-related downregulation of RMR has been implicated in suboptimal weight loss and weight regain after nonsurgical weight loss, defense against AT may underpin the durable weight loss after laparoscopic Roux-en-Y gastric bypass (LRYGB) and other bariatric surgeries. However, methodological differences across the few studies that have evaluated postoperative AT limit interpretation as to the effects of these procedures on RMR. ObjectiveTo quantify AT 6 months after LRYGB and laparoscopic adjustable gastric banding (LAGB). SettingThe study was conducted in a large university hospital in the United States. MethodsChanges in body composition and RMR were assessed in 13 severely obese adults 6 months after LRYGB (n = 8) and LAGB (n = 5). AT was calculated as the difference between measured RMR and RMR predicted from LBM, FM, age, and sex before and after surgery. ResultsRMR significantly decreased after LRYGB (−270±96 kcal/d, P<.01) but not after LAGB. Despite significantly greater reductions in weight, FM, and LBM with LRYGB than LAGB, AT responses after LRYGB (15±110 kcal/d, P = .7) and LAGB (42±97 kcal/d, P = .4) were similar (P = .7). ConclusionDespite significant weight and body composition changes, AT was minimal after LRYGB. A blunting of AT may be an additional mechanism that favors sustainable weight loss with LRYGB.

Efficacy of anamorelin in cachectic patients with non-small cell lung cancer (NSCLC) and low BMI (&lt; 20 kg/m2): Post-hoc analysis of two phase III studies.

203 Background: Patients with advanced cancer frequently experience anorexia/cachexia, which can be characterized by weight loss or low BMI, and is associated with reduced function and quality of life. The randomized, phase III, double-blind ROMANA 1 [NCT01387269; N = 484] and ROMANA 2 [NCT01387282; N = 495]) trials in cachectic NSCLC patients demonstrated that the ghrelin receptor agonist anamorelin improved LBM, body weight, fat mass (FM), and symptom burden compared with placebo, and was well tolerated. The aim of this analysis was to assess the response to anamorelin specifically in patients with BMI below 20 kg/m2. Methods: Stage III/IV NSCLC patients with cachexia ( ≥ 5% weight loss during prior 6 months or BMI &lt; 20 kg/m2) were randomly assigned (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. A post-hoc pooled analysis of efficacy data from both trials was conducted in patients with BMI &lt; 20 kg/m2 (N = 182) and with BMI ≥ 20 kg/m2(N = 647). Endpoints included changes in lean body mass (LBM), fat mass (FM), and changes in self-reported anorexia/cachexia symptoms/concerns and fatigue. Results: Compared with placebo, anamorelin significantly increased LBM both in patients with low BMI (treatment difference: 1.71 kg [95% CI 0.88 – 2.54]) and in those with normal/high BMI (1.47 kg [1.00 - 1.94]) (p &lt; 0.001). Greater increases in FM were observed in the BMI &lt; 20 kg/m2 (1.66 kg [0.86 – 2.46], p &lt; 0.001) than in the BMI ≥ 20 kg/m2 subgroup (0.79 kg [0.30 - 1.28], p = 0.002). Significant improvements in anorexia/cachexia symptoms/concerns were observed in the BMI &lt; 20 kg/m2 subgroup (5.27 [2.11 - 8.43], p = 0.001), while in the BMI ≥ 20 kg/m2 subgroup these were not significant (0.91 [(-0.56) - 2.37], p = 0.224). In patients with low BMI, anamorelin also improved fatigue (3.94 [0.56 – 7-32], p = 0.023), while this was not significant in patients with BMI ≥ 20 kg/m2 (-0.42) [(-2.07) – 1.23], p = 0.616). Conclusions: In patients with BMI &lt; 20 kg/m2 anamorelin increased lean and fat mass as well as improved anorexia/cachexia symptoms/concerns. Additionally, improvements in fatigue were also noted in patients with BMI &lt; 20 kg/m2. Clinical trial information: NCT01387282; NCT01387269.

Correction of Hypothyroidism Leads to Change in Lean Body Mass without Altering Insulin Resistance

Background: Hypothyroidism is associated with insulin resistance, dyslipidemia, and abnormal body composition. This study assessed changes in body composition and insulin resistance after thyroxine (T₄) replacement in overt hypothyroidism. Methods: In this prospective longitudinal study carried out in a tertiary care center, adult nondiabetic patients with overt hypothyroidism were rendered euthyroid on T₄. Anthropometry including skinfold thickness (SFT) at the triceps and subscapularis was recorded. Patients underwent testing for fasting plasma glucose, creatinine, serum insulin, T₄, thyrotropin (TSH) and body composition analysis by dual-energy X-ray absorptiometry (DEXA) both before and at 2 months after restoration to the euthyroid state. Results: Twenty-seven patients (20 female and 7 male) aged 35.3 ± 11.0 years (min-max: 17-59 years) with overt hypothyroidism were recruited. Serum T₄ at the time of recruitment was 48.9 ± 24.6 nmol/l (normal range = 64.4-142 nmol/l). All patients had TSH ≥50 µIU/l. Following treatment, there was a mean body weight reduction of 1.7 kg (p = 0.01). Waist circumference as well as triceps and subscapularis SFT decreased significantly (p < 0.001). There was no change in fat mass (FM), percentage of fat (%FM) or bone mineral content in any of the specified regions or in the body as a whole. In contrast, mean lean body mass (LBM) decreased significantly by 0.8 kg (p < 0.01) in the trunk and 1.3 kg (p < 0.01) in the whole body. Insulin resistance and level of glycemia were not affected by treatment with T₄. Conclusion: LBM decreases significantly without affecting FM after correction of hypothyroidism. Insulin resistance was not influenced by T₄ treatment.

Protein Supplementation Has Minimal Effects on Muscle Adaptations during Resistance Exercise Training in Young Men: A Double-Blind Randomized Clinical Trial

Background: To our knowledge the efficacy of soy-dairy protein blend (PB) supplementation with resistance exercise training (RET) has not been evaluated in a longitudinal study.Objective: Our aim was to determine the effect of PB supplementation during RET on muscle adaptation.Methods: In this double-blind randomized clinical trial, healthy young men [18–30 y; BMI (in kg/m2): 25 ± 0.5] participated in supervised whole-body RET at 60–80% 1-repetition maximum (1-RM) for 3 d/wk for 12 wk with random assignment to daily receive 22 g PB (n = 23), whey protein (WP) isolate (n = 22), or an isocaloric maltodextrin (carbohydrate) placebo [(MDP) n = 23]. Serum testosterone, muscle strength, thigh muscle thickness (MT), myofiber cross-sectional area (mCSA), and lean body mass (LBM) were assessed before and after 6 and 12 wk of RET.Results: All treatments increased LBM (P < 0.001). ANCOVA did not identify an overall treatment effect at 12 wk (P = 0.11). There tended to be a greater change in LBM from baseline to 12 wk in the PB group than in the MDP group (0.92 kg; 95% CI: −0.12, 1.95 kg; P = 0.09); however, changes in the WP and MDP groups did not differ. Pooling data from combined PB and WP treatments showed a trend for greater change in LBM from baseline to 12 wk compared with MDP treatment (0.69 kg; 95% CI: −0.08, 1.46 kg; P = 0.08). Muscle strength, mCSA, and MT increased (P < 0.05) similarly for all treatments and were not different (P > 0.10) between treatments. Testosterone was not altered.Conclusions: PB supplementation during 3 mo of RET tended to slightly enhance gains in whole-body and arm LBM, but not leg muscle mass, compared with RET without protein supplementation. Although protein supplementation minimally enhanced gains in LBM of healthy young men, there was no enhancement of gains in strength. This trial was registered at clinicaltrials.gov as NCT01749189.

Cross-sex hormone therapy in transgender persons affects total body weight, body fat and lean body mass: a meta-analysis.

Weight gain and body fat increase the risk of cardiometabolic disease. Cross-sex hormone therapy in transgender persons leads to changes in body weight and body composition, but it is unclear to what extent. We performed a meta-analysis to investigate the changes in body weight, body fat and lean body mass during cross-sex hormone therapy in transgender persons. We searched the PubMed database for eligible studies until November 2015. Ten studies reporting changes in body weight, body fat or lean mass in hormone naive transgender persons were included, examining 171 male-to-female and 354 female-to-male transgender people. Pooled effect estimates in the male-to-female group were +1.8kg (95% CI: 0.2;3.4) for body weight, +3.0kg (2.0;3.9) for body fat and -2.4kg (-2.8; -2.1) for lean body mass. In the female-to-male group, body weight changed with +1.7kg (0.7;2.7), body fat with -2.6kg (-3.9; -1.4) and lean body mass with +3.9kg (3.2;4.5). Cross-sex hormone therapy increases body weight in both sexes. In the male-to-female group, a gain in body fat and a decline in lean body mass are observed, while the opposite effects are seen in the female-to-male group. Possibly, these changes increase the risk of cardiometabolic disease in the male-to-female group.

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation.

BackgroundConcurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss.Main BodyLoss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population.ConclusionPatients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

Long-term activation of PKA in β-cells provides sustained improvement to glucose control, insulin sensitivity and body weight

ABSTRACTType 2 diabetes is associated with obesity, insulin resistance and β-cell failure. Therapeutic aims are to reduce adiposity, improve insulin sensitivity and enhance β-cell function. However, it has been proposed that chronically increasing insulin release leads to β-cell exhaustion and failure. We previously developed mice to have increased activity of the cAMP-dependent protein kinase (PKA), specifically in β-cells (β-caPKA mice). β-caPKA mice have enhanced acute phase insulin release, which is the primary determinant of the efficacy of glucose clearance. Here these mice were used to determine the sustainability of enhanced insulin secretion, and to characterize peripheral effects of enhanced β-cell function. Increased PKA activity was induced by tamoxifen administration at 10 weeks of age. Male mice were aged to 12 months of age and female mice to 16 months. Glucose control in both male and female β-caPKA mice was significantly improved relative to littermate controls with ad libitum feeding, upon refeeding after fasting, and in glucose tolerance tests. In female mice insulin release was both greater and more rapid than in controls. Female mice were more insulin sensitive than controls. Male and female β-caPKA mice had lower body weights than controls. DEXA analysis of male mice revealed that this was due to reduced adiposity and not due to changes in lean body mass. This study indicates that targeting β-cells to enhance insulin release is sustainable, maintains insulin sensitivity and reduces body weight. These data identify β-cell PKA activity as a novel target for obesity therapies.

Body Composition, But Not Gender, Predicts In-Season Changes in Aerobic Fitness in Collegiate Athletes

The relationship between in-season changes in aerobic fitness and body composition in collegiate athletes is poorly defined. PURPOSE: To evaluate in-season changes in aerobic fitness among collegiate athletes, and how these are influenced by gender, sport and body composition. METHODS: 50 NCAA Division 1 athletes [23 female (11 hockey, 12 soccer), 27 male (11 hockey, 16 soccer)] completed testing immediately before and after their competitive seasons for determination of lean body mass (LBM) and percentage body fat (BF%) by dual-energy x-ray absorptiometry (DXA) and maximal treadmill testing for maximal aerobic capacity (VO2max), time to exhaustion (Tmax), and ventilatory threshold (VT). Pre- and post-season fitness and body composition values were compared using paired t-tests. Multivariable regression analysis was used to identify independent predictors of in-season change in body composition using gender and sport as covariates, as well as in-season changes in fitness measures using sport, gender and body composition as covariates. RESULTS: Compared to pre-season, post-season values for the entire group were lower for VO2max (4.30±0.88 v 4.08±0.86 L/min, p=0.002), and unchanged for Tmax (16.5±2.2 v 16.1±2.3 min, p=0.13), VT (3.05±0.77 v 3.15±0.66 L/min, p=0.18), BF% (19.1±6.8 v 19.4±6.5 %, p=0.39) and LBM (56.7±10.5 v 56.3±9.8 kg, p=0.48). (p>0.05 for all). LBM was a significant, independent predictor of in-season changes in VO2max (r2=0.33, p<0.001), Tmax (r2=0.19, p=0.003) and VT (r2=0.21, p=0.003). In-season change in BF% was not related to VO2max (r2=0.04, p=0.29) or VT (r2=0.03, p=0.51), but was a strong predictor of changes in Tmax (r2=0.32, p<0.001). Gender and sport were not related to in-season changes in body composition or fitness variables (p>0.05 for all). CONCLUSION: In collegiate intermittent sport athletes, in-season change in LBM explains a significant portion of changes in VO2max and VT, whereas in-season changes in Tmax are independently predicted by changes in both LBM and BF%. In-season changes in aerobic fitness and body composition do not differ across sport or gender. This suggests that efforts to influence body composition during the competitive season can significantly impact aerobic fitness in intermittent sport athletes.

Dietary Variety and Decline in Lean Mass and Physical Performance in Community-Dwelling Older Japanese: A 4-year Follow-Up Study.

To examine associations of dietary variety with changes in lean mass and physical performance during a 4-year period in an elderly Japanese population. Four-year prospective study. The Hatoyama Cohort Study and Kusatsu Longitudinal Study, Japan. 935 community-dwelling Japanese aged 65 years or older. Dietary variety was assessed using a 10-item food frequency questionnaire. Body composition was determined by multifrequency bioelectrical impedance analysis, and physical performance (grip strength and usual gait speed) was measured in surveys at baseline and 4 years later. Longitudinal analysis included only participants who were originally in the upper three quartiles of lean body mass, appendicular lean mass, grip strength, and usual gait speed. The outcome measures were decline in lean body mass, appendicular lean mass, grip strength, and usual gait speed, defined as a decrease to the lowest baseline quartile level at the 4-year follow-up survey. Associations of dietary variety with the outcome measures were examined by logistic regression analysis adjusted for potential confounders. In the fully adjusted model, the odds ratios for decline in grip strength and usual gait speed were 0.43 (95% confidence interval, 0.19-0.99) and 0.43 (confidence interval, 0.19-0.99), respectively, for participants in the highest category of dietary variety score as compared with those in the lowest category. Dietary variety was not significantly associated with changes in lean body mass or appendicular lean mass. Among older adults, greater dietary variety may help maintain physical performance, such as grip strength and usual gait speed, but not lean mass.

Investigating the clinical significance of body composition changes in patients undergoing chemoradiation for oropharyngeal cancer using analytic morphomics.

BackgroundThe purpose is to investigate the clinical significance of body morphomics changes in stage III–IV oropharyngeal cancer patients during concurrent chemoradiotherapy (CRT).MethodsFifty patients who underwent CRT were selected for body composition analyses by either availability of pre/post treatment DEXA scans or a novel CT-based approach of body morphomics analysis (BMA). BMA changes (lean psoas and total psoas area) were compared to total lean body mass changes by DEXA scans using two-sample t tests. Pearson correlation was used to compare the BMA measures to head and neck specific quality of life outcomes. Cox hazards model was used to predict mortality and tumor recurrence.ResultsClinically significant declines in total psoas area and lean body mass of similar magnitude were observed in both BMA and DEXA cohorts after CRT. Loss of psoas area (P < 0.05) was associated with greater frailty and mobility issues (3 out of 15 UWQOL domains). Total psoas area is more sensitive for local recurrence than weight changes and T-stage on multivariate analyses.ConclusionsBMA specifically evaluating psoas area appears to correlate with head and neck cancer quality of life physical domains. Pre- and post-treatment total psoas area at L4 appears prognostic for tumor recurrence.

Changes in Protein Turnover, Hormonal Status, and Body Composition during Physiologically Demanding Military Training

Physiological stress imposed during short‐term military training is often severe and intentional; producing a catabolic state and loss of lean body mass (LBM). The extent to which this occurs and metabolic responses that may contribute to the loss of LBM are not well characterized. This study examined body composition, whole‐body protein turnover (15N‐alanine), testosterone and cortisol before (BASELINE) and after (POST) 7 days of Survival, Evasion, Resistance, and Escape (SERE) School in 68 male US Marines (mean ± SD, 25 ± 2 y, 83.7 ± 9.1 kg). Total body mass (TBM) was 7% lower (−2.7 ± 1.4 kg fat and −3.1 ± 1.7 kg LBM), proteolysis 28% higher and net protein balance 132% lower POST‐SERE (P &lt; 0.05) compared to BASELINE. Decrements in testosterone POST‐SERE (−42%; −221 ± 136 ng/dL; P &lt; 0.05) were inversely related with increased proteolysis (r = −0.30; P &lt; 0.05) and protein synthesis (r = −0.28; P &lt; 0.05). Percent changes in testosterone were associated with percent loss of TBM (r = 0.37; P &lt; 0.05) and LBM (r = 0.31; P &lt; 0.05). Cortisol changes during SERE were associated with changes in protein synthesis (r = 0.26; P &lt; 0.05). Percent change in cortisol was inversely associated with percent change in fat mass (r = −0.34, P &lt; 0.05) and tended to predict the percent change in LBM (r = 0.22; P = 0.07). The physiological stress during SERE elicits a hypogonadal state and catabolism of LBM. Decrements in testosterone were quantitatively associated with the increase in proteolysis and loss of LBM.Support or Funding InformationSupported by USAMRMC

Lean body mass change over 6 years is associated with dietary leucine intake in an older Danish population.

Higher protein intake, and particularly higher leucine intake, is associated with attenuated loss of lean body mass (LBM) over time in older individuals. Dietary leucine is thought to be a key mediator of anabolism. This study aimed to assess this relationship over 6 years among younger and older adult Danes. Dietary leucine intake was assessed at baseline and after 6 years in men and women, aged 35-65 years, participating in the Danish cohort of the WHO-MONICA (Multinational MONItoring of trends and determinants in CArdiovascular disease) study (n 368). Changes in LBM over the 6 years were measured by bioelectrical impedance using equations developed for this Danish population. The association between leucine and LBM changes was examined using multivariate linear regression and ANCOVA analyses adjusted for potential confounders. After adjustment for baseline LBM, sex, age, energy intake and physical activity, leucine intake was associated with LBM change in those older than 65 years (n 79), with no effect seen in those younger than 65 years. Older participants in the highest quartile of leucine intake (7·1 g/d) experienced LBM maintenance, whereas lower intakes were associated with LBM loss over 6 years (for trend: β=0·434, P=0·03). Sensitivity analysis indicated no effect modification of sex or the presence of CVD. Greater leucine intake in conjunction with adequate total protein intake was associated with long-term LBM retention in a healthy older Danish population. This study corroborates findings from laboratory investigations in relation to protein and leucine intakes and LBM change. A more diverse and larger sample is needed for confirmation of these results.

Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials

Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia. ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index <20 kg/m(2)) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282. From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0·99 kg [95% CI 0·61 to 1·36] vs -0·47 kg [-1·00 to 0·21], p<0·0001) and ROMANA 2 (0·65 kg [0·38 to 0·91] vs -0·98 kg [-1·49 to -0·41], p<0·0001). We noted no difference in handgrip strength in ROMANA 1 (-1·10 kg [-1·69 to -0·40] vs -1·58 kg [-2·99 to -1·14], p=0·15) or ROMANA 2 (-1·49 kg [-2·06 to -0·58] vs -0·95 kg [-1·56 to 0·04], p=0·65). There were no differences in grade 3-4 treatment-related adverse events between study groups; the most common grade 3-4 adverse event was hyperglycaemia, occurring in one (<1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2. Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia. Helsinn Therapeutics.