Loss Of Lean Mass Research Articles

A double-blind, placebo-controlled randomized phase II study: Evaluating the effect of curcumin for treatment of cancer anorexia-cachexia syndrome in solid cancer patients.

e23151 Background: Cancer anorexia–cachexia syndrome (CACS) is common among patients with advanced solid cancer and associated with poor prognosis. CACS is a hypercatabolic state, which comprises adipose tissue and skeletal muscle loss, which is characterized by negative protein and energy balance, loss of lean body mass and adipose tissue. Also, CACS increase systemic inflammation. The treatment of CACS is still unclear. Curcumin has been shown anti-cancer and anti-inflammatory effects, including attenuation of CACS in animal models. Therefore, clinical study of curcumin for CACS is required. Methods: This is randomized, double-blind, placebo-controlled phase ll study, 52 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 400 mg twice daily) or placebo for 8 weeks. The primary end point was body tissue composition and the secondary end points were body weight and body mass index, Hand grip muscle strengthening, safety and toxicity. Results: All parameters of body compositions were not statistically significant different between two groups: curcumin group and placebo group, which were consist body fat mass -0.9, SEM = 0.94 versus –1.65, SEM = 1 ( p-value = 0.58), skeletal muscle mass -0.17, SEM = 0.49 versus +0.4, SEM = 0.52 ( p-value = 0.42) and percent body fat –1.0, SEM = 0.65 versus -0.1, SEM = 0.68 ( p-value = 0.3) including with basal metabolic rate -5.3, SEM = 18 versus +18.3, SEM = 19 ( p-value = 0.37). The average of weight loss was also not statistically significant different between two groups, -1.04, SEM = 0.63 in curcumin group versus –1.15, SEM = 0.61 in placebo group, ( p-value = 0.9). Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [right hand: -2.09 in curcumin versus -3.68 in placebo; p = 0.46], [left hand: -1.24 versus -5.04; p-value = 0.12], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly. Conclusions: Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss and basal metabolic rate. Further investigations should be explored.

Effect of free amino acids mix with medium triglycerides and Withania somnifera on cancer cachexia.

e23140 Background: Cancer cachexia is a multifactorial syndrome involving systemic inflammation, negative protein and energy balance, and involuntary loss of lean muscle mass. It not only adversely affects quality of life but also leads to poor responses to chemotherapy and reduced survival rates. Conventional nutritional support has not been successful in cancer cachexia and most commercially available formulas have shown little to no effect on cancer cachexia. This study assessed nutritional benefits of E2 Energy, an amino acid (AA) supplement powder enriched with branched-chain AAs, medium-chain triglycerides, and Withania somnifera, on body weight, lean muscle mass, and cancer-related piper fatigue score. Methods: This prospective, open-label preliminary feasibility study was conducted in patients receiving active treatment for cancer (e.g. chemotherapy, radiation, targeted therapy, or hormone therapy) with documented evidence of significant weight loss. Patients were evaluated at baseline and at the end of treatment (12 weeks) for lean muscle mass as measured by bioimpedance analysis, body weight, C-reactive protein (CRP), serum albumin, fatigue as measured by Piper Fatigue Scale (PFS), and proinflammatory cytokines (IL-1, IL-2, IL-6, and TNF-α). Being a pilot study, enrollment was restricted to approximately 30 patients with focus on descriptive statistics rather than formal tests of hypotheses. Results: We analyzed data of 15 patients who completed at least 6 weeks of treatment. Treatment with AA powder increased lean muscle mass in 12 (80%) patients. Similarly, PFS scores improved in 14 (93.33%) patients. Overall, in 6 patients (40%), body weight either remained stable or increased from baseline values. Six patients presented abnormal cytokine levels at baseline; however, their results at follow-up were unavailable, thus making interpretation inconclusive. Conclusions: Treatment with AA powder supplement may prevent loss in lean muscle mass, reduce fatigue, and curtail weightloss. However, these results must be substantiated in large well-designed (randomized) studies.

Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism.

Purpose To explore the changes in FSP27 expression and fat metabolism in adipose tissue and their relationship after bariatric surgery in rats. Method Food intake, body weight, triglyceride content, fat distribution, and fat cell morphology were evaluated in rats grouped into control, sham, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) groups. Immunohistochemistry and western blotting were used to detect protein expression and real-time PCR was used to detect mRNA expression. Mouse 3T3-L1 preadipocytes were used to assess the effects of different energy levels and nutrient factors on FSP27 in adipocytes. Result Food intake, body weight, and triglyceride levels were reduced in RYGB and SG rats within 28 days after surgery, with a more pronounced effect in the RYGB group. Weight loss was mainly due to loss of fat mass rather than loss of lean mass, with the most pronounced decrease in trunk fat. FSP27 expression increased in lean rat adipocytes accompanied by increased lipid droplets (LDs). In SG and RYGB rats, the FSP27 protein concentration gradually increased in white adipose tissue (WAT) after operation. Hormone-sensitive lipase (HSL), p-HSL/HSL, Adipose Triglyceride Lipase (ATGL), and Comparative Gene Identification-58 (CGI-58) gradually decreased in SG and RYGB rats, but they were always higher than in control and sham animals. FSP27 was also decreased in 3T3-L1 adipocytes of animals with a high-energy diet. Conclusion FSP27 is associated with rat lipid metabolism and its expression varies with energy and nutrient supply. It can inhibit excessive hydrolysis and fat accumulation by regulating HSL and ATGL expression and by mediating LDs formation.

Can we cure type 2 diabetes?

Can we cure type 2 diabetes?

MON-098 FSH and Body Composition in Older Adults

Background: Common changes with menopause and aging include an increase in visceral adiposity and loss of lean body mass. Declines in sex steroid hormones contribute to these body composition changes, but emerging evidence also implicates increased pituitary production of follicle stimulating hormone (FSH). Blocking FSH action with an FSH-β subunit antibody reduced adiposity and increased lean body mass in ovariectomized female mice, and both male and female intact mice (Liu Nature 2017). Some, but not all, clinical observational studies have demonstrated positive associations between FSH and measures of adiposity (Zaidi Endocrinology 2018). Objective: To investigate the associations between endogenous FSH levels and measures of body composition in older adults from the AGES-Reykjavik cohort, independent of sex steroid hormones. Methods/Results: Participants were recruited from the AGES-R study, excluding those using sex steroid hormone agonists or antagonists. FSH (ELISA), total estradiol and total testosterone (GC/MS) were measured from fasting serum. Total body fat (kg), total body lean mass (kg), and appendicular lean mass (kg) were measured with total body DXA. Appendicular lean mass index (ALMI) was calculated as appendicular lean mass/height2 (kg/m2). Visceral adipose tissue (VAT) area (cm2) and subcutaneous adipose tissue (SAT) area (cm2) were measured with abdominal CT. Linear regression analyses of FSH in association with body composition parameters were performed, stratified by gender, both unadjusted and adjusted for age, visit window, BMI, total estradiol and total testosterone levels. Among the 245 men, the mean age was 82.4 (SD 4.0) years, mean BMI was 26.7 (SD 3.6) kg/m2 and mean FSH 19.0 (SD 16.9) IU/L . Among the 238 women, the mean age was 80.6 (SD 4.0) years, mean BMI 27.4 (SD 4.1) kg/m2 and mean FSH 71.6 (SD 23.2) IU/L. In models adjusted for age, visit window, BMI, estradiol and testosterone, there were no significant associations between FSH and any measure of body composition in men. In adjusted models in women, each SD increase in FSH was associated with a 2.67% greater SAT area (p=0.03) but no significant difference in VAT area or total body fat. Conversely, each SD increase in FSH was associated with a1.62% lower total body lean mass (p=0.005) in women, but no significant difference in ALMI. Conclusion: Consistent with preclinical models, we found higher FSH to be associated with greater subcutaneous adiposity and lower lean body mass in older women. We found no associations between FSH and measures of body composition in older men. Further research is needed to determine whether FSH-directed therapy may be an effective means of combatting the body composition changes associated with menopause.

MON-094 Aromatase Inhibitors and Weight Loss in Severely Obese Male Veterans with Hypogonadism: A Randomized Clinical Trial

Introduction: The prevalence of hypogonadism among males is influenced by aging and obesity. The increased expression of the aromatase enzyme in the adipose tissue of obese men leads to a high conversion of androgens to estrogen, exerting a negative feedback on the hypothalamus-pituitary-gonadal axis contributing to hypogonadotropic hypogonadism. Our objective is to determine if anastrozole, an aromatase inhibitor (AI), in combination with weight loss could have a positive effect on symptoms of hypogonadism and muscle strength, and to evaluate the impact on bone mineral density (BMD) and bone quality. Methods: Twenty-three obese men (BMI≥35kg/m2) aged 35-65 years old with hypogonadotropic hypogonadism were randomized in a 6-month double-blind placebo-controlled trial of weight loss (with diet and exercise) plus either anastrozole (n=12) or placebo (PBO) (n=11). The inclusion criteria were morning testosterone <300 ng/mL (mean of 2 measurements), estradiol >10.9 pg/mL, and LH <9 IU/L. The hypogonadal symptoms were evaluated by 4 questionnaires: IPSS, qADAM, IWQOL, and IIEF-5, and the muscle strength was measured by Biodex machine. The body composition and BMD were determined by DXA, and the bone microarchitecture by HR-pQCT. The hormonal levels, hypogonadal symptoms, muscle strength, and body composition were assessed at baseline, 3 months, and 6 months; whereas the BMD and bone microarchitecture were evaluated at baseline and 6 months. Results: Average weight loss at 6 months was -7.0±6.9% in the AI group vs -2.4±2.9% in the PBO group (p=0.12). At 6 months, testosterone levels increased by +95.2±66.3% in the AI group vs +0.8±29.4% in the PBO group (p<0.01), and estradiol levels decreased by -60.9±21.8% in the AI group vs +5.2±18.6% in the PBO group (p<0.01). LH levels increased by +66.6±89.3% in patients treated with AI and decreased by -4.8±24.2% in those who received PBO (p=0.06). There was no improvement of symptoms in the AI group (+18.9±48.7%) vs placebo (+7.8±34.1%) based on IIEF-5 questionnaire (p=NS) and no significant difference in muscle strength between groups. Lean mass was better preserved in the AI compared to the PBO group (-0.73±2.5% vs -3.60±2.70%, respectively; p=0.05). There was no change in spine BMD in the AI compared to the PBO group (-0.71±3.32% vs +3.22±4.90%, respectively; p=0.08), and no change in tibial trabecular bone area in the AI compared to the decrease in the PBO group (+0.12±0.68% vs -2.09±2.20%, respectively; p<0.05). Conclusion: AI plus weight loss improves the hormonal profile of severely obese men with hypogonadism and prevents weight loss-induced loss of lean mass without causing major side effect on BMD within 6 months of therapy. However, in this short-term study with limited sample size, we found no significant improvement in symptoms of hypogonadism. Further large and long-term trials are needed to confirm these results.

Body composition indices in Brazilian adults: age-specific and sex-specific percentile curves.

To establish percentile curves for measures and indices of body composition by age and sex and compare them with data from other ethnic groups. Cross-sectional, population-based study with adults aged 20-59 years (n = 689). Percentile curves adjusted by a third degree polynomial function were constructed for skeletal mass index (SMI), fat mass index, body fat, and load-capacity metabolic indices (LCMI) based on dual-energy X-ray absorptiometry (DXA). SMIweight and SMIBMI showed decline from the third decade of life in both sexes, whereas SMIheight was not able to identify lean mass loss over the ages studied. There was a slight drop at the end of the fifth decade (50-59 years) in men. Among Americans and Chinese, the 50th percentile curve of SMIheight showed an earlier decline. The estimates of adiposity and LCMI curves peaked between 40-49 years and Americans and Chinese maintained an upward curve throughout adulthood. The data and curves showed that the SMI adjusted for BMI and body weight were more adequate in detecting the decline of lean mass in adults due to aging. In contrast, SMIheight had a positive correlation with age and its curve increased throughout the evaluated age groups. The results contribute to the evaluation to the nutritional status of adults and to the prevention and treatment of outcomes related to adiposity and deficit lean mass.

Metabolic and skeletal homeostasis are maintained in full locus GPRC6A knockout mice

The G protein-coupled receptor class C, group 6, subtype A (GPRC6A) is suggested to have a physiological function in glucose and bone metabolism, although the precise role lacks consensus due to varying findings in different knockout (KO) mouse models and inconsistent findings on the role of osteocalcin, a proposed GPRC6A agonist. We have further characterized a full locus GPRC6A KO model with respect to energy metabolism, including a long-term high-dose glucocorticoid metabolic challenge. Additionally, we analyzed the microarchitecture of tibiae from young, middle-aged and aged GPRC6A KO mice and wildtype (WT) littermates. Compared to WT, vehicle-treated KO mice presented with normal body composition, unaltered insulin sensitivity and basal serum insulin and glucose levels. Corticosterone (CS) treatment resulted in insulin resistance, abnormal fat accrual, loss of lean mass and suppression of serum osteocalcin levels in both genotypes. Interestingly, serum osteocalcin and skeletal osteocalcin mRNA levels were significantly lower in vehicle-treated GPRC6A KO mice compared to WT animals. However, WT and KO age groups did not differ in long bone mass and structure assessed by micro-computed tomography. We conclude that GPRC6A is not involved in glucose metabolism under normal physiological conditions, nor does it mediate glucocorticoid-induced dysmetabolism in mice. Moreover, GPRC6A does not appear to possess a direct, non-compensable role in long bone microarchitecture under standard conditions.

Skeletal Muscle Function is Impaired in Mice Following Surgical Weight Loss

Limb skeletal muscle mass losses in the year following bariatric surgery are far greater than the loss of lean mass experienced by inactive persons during the typical aging process. This is a clinical concern, since loss of skeletal muscle mass may have long term effects that attenuate many of the benefits associated with marked weight loss (such as sarcopenia, frailty and loss of mobility). Here, we use a mouse model of bariatric surgery (gastric sleeve) to test the hypothesis that surgical weight loss impairs skeletal muscle function. Sixteen‐week‐old male C57BL6/J mice with diet‐induced obesity (DIO; 5.21 kCal/g, 60% fat, 20% carbohydrate, 20% protein; D12492 Research Diets) were randomized into groups receiving either gastric sleeve surgery (GS; 80% resection of the greater curvature of the stomach) or sham surgery (DIO‐sham; laparotomy). A third group of age‐matched lean mice were included as a non‐surgical, non‐obese comparison group (3.82 kCal/g, 10% fat, 70% carbohydrate, 20% protein; D12450J Research Diets). Following surgery, GS mice rapidly lost 20% of their pre‐surgery weight, reducing their initial fat mass by 53% and lean mass by 20%, as measured by EchoMRI. Loss of lean mass was associated with a reduction in grip strength six‐weeks post‐surgery (−10%, p=0.04), compared to DIO‐sham, despite regain of most of the initial lean mass losses. GS mice had reduced total energy expenditure compared to DIO‐sham, as measured by indirect calorimetry at both 22°C (−7% during the light phase, p=0.0015 and −11% during the dark phase, p=0.009) and at 28°C (−7% during the light phase only, p=0.05). No differences in ambulatory activity were observed between groups. These findings, although preliminary, suggest that bariatric surgery causes molecular adaptations in the skeletal muscle that may not be easily reversed once initial lean mass losses are restored. Further work will identify whether surgical weight loss causes alterations in protein breakdown/synthesis and other metabolic adaptations that affect long‐term skeletal muscle function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Increased Protein Intake Prevents Elevations in Sclerostin during Short‐Term Diet‐ and Exercise‐Induced Weight Loss

Caloric‐restriction is necessary for efficacious weight loss, but can lead to unwanted losses of lean mass and bone mineral content. High‐protein diets have been shown to protect lean mass during caloric‐restriction and may have similarly preservative effects on bone either through attenuating increases in bone resorption or elevating bone formation.ObjectivesTo determine whether increasing protein intake, in combination with daily aerobic exercise, attenuates elevations in bone resorption markers and reductions in bone formation markers during short‐term severe caloric‐restriction in healthy, active men. We hypothesized increasing protein intake would attenuate elevations in sclerostin and c‐terminal telopeptide (CTX) while maintaining levels of procollagen type I propeptide (P1NP).MethodsIn this randomized crossover trial, participants underwent three conditions: caloric‐restriction with low protein intake (CRLP; 0.8 g/kg body weight (BW)); caloric‐restriction with high protein intake (CRHP; 1.7 g/kg BW) and energy balance control (CON; 1.7 g/kg BW). Caloric restriction was achieved by reducing energy availability, calculated as the difference between dietary energy intake and exercise energy expenditure, to 15 kcal/kg fat‐free mass (FFM), whereas energy availability was maintained at 40 kcal/kg FFM in CON. Throughout all conditions, participants completed daily supervised exercise sessions on a bicycle ergometer set to expend 15 kcal/kg FFM. Before and after each five‐day condition, body composition was assessed via bioimpedance analysis and markers of bone formation and resorption were assessed from fasting blood samples.ResultsBody weight decreased (p &lt; 0.001) in CRLP [−1.97 ± 0.22 kg] and CRHP [−1.80 ± 0.52 kg], but remained stable in CON. Loss of fat mass was significant in CRHP [−1.14 ± 0.23 kg, p &lt; 0.05] but not in CRLP [−0.57 ± 0.48 kg]. Sclerostin was elevated above baseline levels only in CRLP [19.7 ± 22.5 %, p &lt; 0.05] but not in CRHP [3.2 ± 18.3 %] or CON [3.7 ± 26.1 %]. CTX was reduced in CON [−8.9 ± 9.8 %, p &lt; 0.05] but did not change in CRHP [0.1 ± 5.4 %] or CRLP [3.8 ± 14.7 %]. P1NP did not change significantly in any group.ConclusionsElevating protein intake and performing daily aerobic exercise during five days of severe caloric restriction suppressed the elevation in sclerostin, a bone resorption marker, seen in individuals who performed daily aerobic exercise but did not elevate protein intake. This effect mirrors the protective effect of increased protein intake on lean mass.Support or Funding InformationThis work was supported in part by funding from the USDA National Institute of Food and Agriculture (NEB‐36‐083) and a Layman Seed Award from the University of Nebraska Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Anabolic competence: Assessment and integration of the multimodality interventional approach in disease-related malnutrition.

Disease-related malnutrition (DRM) is a frequent clinical problem, characterized by loss of lean body mass and decreased function, including muscle function and immunocompetence. In DRM, nutritional intervention is necessary, but it has not consistently been shown to be sufficient. Other factors, for example, physical activity and hormonal or metabolic influencers of the internal milieu, are also important in the treatment of DRM. A prerequisite for successful treatment of DRM is the positive balance between anabolism and catabolism. The aim of this review was to approach DRM using this paradigm of anabolic competence, for conceptual and practical reasons. Anabolic competence is defined as "that state which optimally supports protein synthesis and lean body mass, global aspects of muscle and organ function, and immune response." Anabolic competence and interdisciplinary, multimodality interventions create a practical foundation to approach DRM in a proactive comprehensive way. Here, we describe the paradigm of anabolic competence, and its operationalization by measuring factors related to anabolic competence and suited for clinical management of patients with DRM.

Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low-dose growth hormone therapy.

The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy. In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow-up data were excluded, and data for 56 patients were analysed. Twenty-six patients who had received GH therapy for more than 6months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5IU/d. Thirty patients who had not previously received GH treatment were included in the non-GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual-energy X-ray-absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) <7.0kg/m2 in males or 5.7kg/m2 in females. Statistical analyses were performed using GraphPad Prism 5.0. Compared to the non-GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non-GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non-GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non-GH-treated patients (P<0.05). The GH group had significantly higher serum levels of both IGF-1 and IGFBP3. Moreover, both IGF-1 and IGFBP3 were significantly correlated with SMI (r2 =0.275, P=0.003, and r2 =0.138, P=0.005, respectively). Our data showed that AGHD patients who received low-dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

Alteration of performance in a mouse model of Emery–Dreifuss muscular dystrophy caused by A-type lamins gene mutation

Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated cardiomyopathy with conduction blocks; however, variable skeletal muscle involvement can be present. Previously, we and other demonstrated altered activity of signaling pathways in hearts and striated muscles of LmnaH222P/H222P mice, a model of autosomal EDMD. We showed that blocking their activation improved cardiac function. However, the evaluation of the benefit of these treatments on the whole organism is suffering from a better knowledge of the performance in mouse models. We show in the present study that LmnaH222P/H222P mice display a significant loss of lean mass, consistent with the dystrophic process. This is associated with altered VO2 peak and respiratory exchange ratio. These results showed for the first time that LmnaH222P/H222P mice have decreased performance and provided a new useful means for future therapeutic interventions on this model of EDMD.

370 Evaluating the Efficacy and Safety of Intraoperative Enteral Nutrition in Critically Ill Burn Patients: A Systematic Review and Meta-Analysis

Large burn injuries incite a hypermetabolic response that increases basal calorie requirements up to 140%. Caloric deficits and resultant malnutrition causes loss of lean body mass that perpetuates an immuno-compromised state and leads to a significant increase in graft failure, wound infections, and mortality. Optimal nutritional therapy reduces such complications, stressing the importance of early enteral nutrition (EN). Perioperative fasting can lead to cumulative caloric deficits over time, which can be ameliorated by intraoperative enteral nutrition (IEN). One concern of IEN is aspiration and an uncertain risk benefit ratio. Because of this, we conducted a systematic review and meta-analysis to evaluate the safety and efficacy of IEN. The guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were employed for this study. A systematic literature search was performed by two independent reviewers using PubMed, Scopus, and OvidSP MEDLINE databases as well as manually checking the reference lists of retrieved articles and reviews once article relevance was determined. We performed a meta-analysis on the incidence of mortality, pneumonia, and wound infections in patients who received IEN. We identified 1,414 non-duplicate articles, of which 56 were included in the full-text analysis. After full-text analysis, five and four articles were included for qualitative and quantitative review, respectively. All articles were Level IV evidence. There was a total of 97 patients that received IEN. Based on the limited sample size from the articles retrieved, there were no statistically significant increases in the risk of mortality (OR=1.3, 95% CI 0.5, 3.3), pneumonia (OR=2.1, 95% CI=0.7, 6.1), or wound infection (OR=0.7, 95% CI, 0.2, 3.2). In all studies, patients receiving IEN were delivered more calories than standard fasting patients. IEN may be safely delivered in select burn patients without an increase in complications, although the studies are limited and of low quality. The benefits of nutritional therapy in burn patients are well-established and indisputable. IEN deserves special attention, as it presents a simple and straightforward means to improve nutritional supplementation and improve hospital outcomes. However, it is not without risk and may be logistically difficult to implement at many institutions due to concerns for aspiration and dogmatic perioperative fasting protocols. Although IEN shows great promise, trials clarifying safety and efficacy are needed before widespread adoption of this practice begins. IEN may be considered on a case-by-case basis in burn patients requiring nutritional therapy.

118 Sarcopenia is Associated with Worse Postoperative Outcomes in Burn Patients

Loss of lean muscle mass has been associated with worse outcomes in cancer patients. Although there have been studies that have examined outcomes related to metabolic derangements in burn patients, the prevalence of sarcopenia and sarcopenic obesity and their effects on operative outcomes of burned patients have yet to be described. Skeletal muscle mass index was measured for patients with ≥20% surface area burn admitted to the ICU with computed tomography scan performed between January 2007 and January 2017. Skeletal muscle area was measured at the L3 level and calculated the skeletal muscle mass index (cm2/m2). Sarcopenia was defined as two standard deviations below the index level defined in healthy adults. Statistical analysis evaluating demographics, co-morbidities and outcomes in relation to sarcopenia was performed. Nineteen patients were included in the study with a mean age of 43.2 (21–67) and 68.4% were male. The mean % burn surface area was 43.9% (20–77.5). Mean number of burn operations per patient was 8.6 (1–27). 47.4% of skin grafts healed after the first attempt and overall healing was 73.7%. Mean length of stay (LOS) was 99.4 days (median 91, 16–257). Mean BMI was 29.3 (21.2–41.8). The prevalence of sarcopenia was 68.4%; 69.2% of males and 66.7% of females. Sarcopenia was associated with overall postoperative complications (p=0.007) and superficial wound infections (p=0.012) and pneumonia (p=0.013). There were 6 (31.5%) patients categorized as having sarcopenic obesity. These patients were more likely to use or have used alcohol (p=0.004, 0.009) and had increased number of overall and burn-specific operations (p=0.006 and 0.011, respectively). They were more likely to have PE (p=0.028). Sarcopenia was not significantly associated with gender, race, co-morbidities, LOS, readmissions or mortality. Our findings suggest that decreased lean muscle mass at time of burn injury is associated with worse postoperative outcomes, especially if the patient is both sarcopenic and obese. Interestingly, co-morbidities and age were not associated with sarcopenia. In these patients, nutritional support was maintained throughout hospitalization. However, it may require interventions targeting muscle strengthening, even during these lengthy hospitalizations to help improve operative outcomes in severely burned patients. This study accomplishes two goals: it highlights the significance of close monitoring of nutritional status on eventual outcomes in Burn Patients. Also, we are describing another method of investigating metabolic studies, not previously applied to Burn Patients, that will allow centers to better care for their patients.

Changes in body composition and weight during the menopause transition.

The relation between the menopause transition (MT) and changes in body composition or weight remains uncertain. We hypothesized that, independent of chronological aging, the MT would have a detrimental influence on body composition. Participants were from the longitudinal Study of Women's Health Across the Nation (SWAN) cohort. We assessed body composition by dual energy x-ray absorptiometry. Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of outcomes as a function of time before or after the final menstrual period (FMP). Covariates were age at FMP, race, study site, and hormone therapy. Fat and lean mass increased prior to the MT. At the start of the MT, rate of fat gain doubled, and lean mass declined; gains and losses continued until 2 years after the FMP. After that, the trajectories of fat and lean mass decelerated to zero slope. Weight climbed linearly during premenopause without acceleration at the MT. Its trajectory became flat after the MT. Accelerated gains in fat mass and losses of lean mass are MT-related phenomena. The rate of increase in the sum of fat mass and lean mass does not differ between premenopause and the MT; thus, there is no discernable change in rate of weight gain at the start of the MT. NIH, Department of Health and Human Services (DHHS), through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women's Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).

SARCOPENIA, SARCOPENIC OBESITY AND FRAILTY; LINKS TO COGNITIVE PERFORMANCE IN ELDERS: Session 412

Background: According to 2011 CDC data, more than 2.6 million adults aged 60 and older with cognitive impairment reported difficulty performing one or more ADLs. There are studies that link cognitive decline and physical impairment in terms of low-level chronic inflammation, oxidative stress, and depression. Skeletal muscle can produce IL-1, IL-6 and other important myokines that have been implicated in cognitive and physical functional degenerative processes. Oxidative stressors have been linked to physical frailty and sarcopenia as well as neurodegenerative processes further worsening cognitive impairment. What are Sarcopenia and Sarcopenic Obesity and its impacts on elders? Sarcopenia is a primary disease of the elderly population, characterized by loss of skeletal muscle mass and function. Sarcopenia is correlated with physical disability, poor quality of life, frailty, cognitive impairment, and death. Age, gender, and level of physical activity are the risk factors for the Sarcopenia. In addition to aging, malignancy and rheumatoid arthritis causes loss of lean body mass and even increase in body fat mass. The loss of muscle mass associated with increased body fat mass i.e. sarcopenic obesity causes weakness in aging. Sarcopenia, with or without obesity, results in impairment of IADL (Instrumental Activity of Daily Living) and eventually ADLs (Activities of Daily Living) among elders and results in need for long-term care and increased cost of health care. What is the link between Sarcopenia and Cognitive Impairment? Sarcopenia has not only has a greater effect on survival but also on cognitive impairment. Sarcopenia has been linked to global cognitive impairment and dysfunction in specific cognitive skills including memory, speed, and executive functions. While obesity may impair the executive functions of aging, the exact mechanism linking obesity to cognitive dysfunction is not clear. Improvement in muscular function of obese older adults has been linked to improvement of executive functions. Obesity and Sarcopenia were associated with the lower executive function such as working memory, mental flexibility, self-control and orientation when assessed independently and even more so when they occurred together. Sarcopenia is highly correlated with frailty and risk of falls in elders; it also represents an important risk factor for disability and mortality. Frailty is an independent predictor of dementia. How do you assess for the Sarcopenia? Sarcopenia with or without obesity can be used in clinical practice to assess the potential risk of cognitive impairment in elders. There are several ways to measure Sarcopenia – DEXA (Dual-Energy X-ray Absorptiometry), biometric impedance analysis (BIA), CT (Computed Tomography) scan and MRI (Magnetic Resonance Imaging). However, assessing BMI and testing grip strength by dynamometry can be easily administered during annual wellness visits to assess the risk of sarcopenic related cognitive impairments. Sarcopenia can be assessed using parameters such as 1) Measure walking speed in elderly (>65 years). If the walking speed is below 0.8 m/s at the 4-m walking test, measure the muscle mass. 2) Hand- grip strength if this value is lower than 20kg in women and 30kg in man then muscle mass must be analyzed. 3) Defining Fat mass and lean body mass using BIA 4) Muscle Mass assessment by DEXA or CT. What is the significance of assessing the Sarcopenia? It is important to identify the risk of cognitive impairment by assessing for the onset of this condition. Preventing or delaying onset will likely enhance survival and reduce the demand for long-term care. Increasing resistance physical training will help to improve physical deconditioning, strengthen skeletal muscle hypertrophy, overcome the pain syndrome and enhance overall mental well-being. Interventions such as resistance exercise and nutritional therapy need to be developed specifically to delay the onset of Sarcopenia. What is the need in the future? Team-based approach including multidisciplinary model involving primary care physicians, geriatric psychiatrists, pain management physicians and physical therapists is required to combat the complex interlinked Sarcopenia associated cognitive impairment. Screening programs that include identification of cognitive and functional impairment in the office setting will serve as the starting point for specific interventions. The training regimen that includes supervision and correct equipment with resistance exercise will be necessary to get proper training and delay the muscle loss in elderly.

Increasing adipose burden in young men with metastatic testicular cancer following front-line cytotoxic chemotherapy.

525 Background: Exposure to cytotoxic chemotherapy (CC) has been observed to be associated with significant changes in body composition, namely marked lean muscle mass losses, with implications for treatment-related toxicity and oncologic outcomes. However, prior studies predominately include elderly patients who, a priori, are at risk for sarcopenia or severe skeletal muscle deficiency. To date, the impact of CC on body composition in young men with testicular cancer remains undefined. Methods: A retrospective analysis of 19 patients with metastatic testicular cancer treated with CC was performed (2015-17). Lumbar skeletal muscle index (SMI), visceral (VAI), subcutaneous (SCAI), and intramuscular adipose (IMAI) indices (cm2/m2), as well as fat-free mass (FFM, kg) and fat mass (FM, kg) were calculated using cross-sectional soft tissue area measurements on pre- and post-CC computed tomography (CT) axial scans and compared using paired Wilcoxon Signed Rank Tests. Results: Median age was 29 years. According to the NHANES FMI-based classification, 5 (26.3%), 9 (47.4%), 4 (21.1%), and 1 (5.3%) patients had normal, excess, class I, and class II obesity, respectively. Median pre- and post-CC BMI was 27.7 vs. 29.6 kg/m2(p = 0.03). Median pre- and post-CC SMI, VAI, SAI, and IAI were 63.5 vs 57.8 (p = 0.14), 19.9 vs 30.8 (p = 0.01), 47.9 vs 58.2 (p = 0.03), and 3.0 vs 5.2 (p = 0.002), respectively. Median muscle density pre- and post-CC were 47.0 vs 43.6 HU (p = 0.002). Pre- and post-chemotherapy FFM were 21.5 vs 19.5 kg, representing an overall median loss of 2.8%, (IQR -10.1, +4.7; Range -49.5 - +16.3; p = 0.14). Conversely, pre- and post-CC FM were 6.6 vs 7.5 kg, representing an overall median gain of 13.3% (IQR -3.3, +17.0; -24.9 - +50; p = 0.01). Median time between imaging assessments was 121 days. Specific median measures of adiposity each increased significantly, such that VIA increased by 29% (p = 0.01), SCAI increased by 39.7% (p = 0.03), and IMIA increased by 39.7% (p = 0.002). Conclusions: While lean muscularity remained stable, we observed significant increases in total body adipose mass with decreased muscle density in this consecutive case series of testicular cancer patients following CC.

The leptin sensitizer celastrol reduces age-associated obesity and modulates behavioral rhythms.

The prevalence of obesity increases with age in humans and in rodents. Age‐related obesity is characterized by leptin resistance and associated with heightened risk of metabolic disorders. However, the effect of leptin resistance per se has been difficult to disentangle from other effects of aging. Here we demonstrate that celastrol, a natural phytochemical that was previously shown to act as a leptin sensitizer, induces weight loss in aged animals, but not in young controls. Celastrol reduces food intake and lowers fasting glucose without affecting energy expenditure. Unexpectedly, administration of celastrol just before the dark period disrupted circadian rhythms of sleep and activity. This regimen was also associated with loss of lean mass an outcome that would not be desirable in elderly patients. Adjusting the timing of celastrol administration by 12 hr, to the beginning of the light period, avoided interference with circadian rhythms while retaining the reductions in body weight and adiposity. Thus, targeting leptin signaling is an effective strategy to ameliorate age‐associated weight gain, and can profoundly impact circadian rhythms.

The Obesity Paradox in Cardiovascular Diseases

The Obesity Paradox in Cardiovascular Diseases