Body Composition Phenotypes Research Articles

Tumour grade and stage are associated with specific body composition phenotypes with visceral obesity predisposing the host to a less aggressive tumour in colorectal cancer

BackgroundSarcopenia, myosteatosis and visceral obesity (VO) are known to negatively impact on outcomes from colorectal cancer (CRC). Little is known about tumour factors associated with these body composition (BC) phenotypes. We aimed to identify whether histopathological tumour characteristics were associated with various BC phenotypes. MethodsA prospectively collected database of patients undergoing surgery for primary CRC at a tertiary referral unit in the United Kingdom was analysed. Sarcopenia, myosteatosis and VO were identified on preoperative CT. Binary logistic regression modelling was performed to determine significant associations between tumour stage, grade and BC phenotype. ResultsFinal analysis included 795 patients; median age 69, 56% male, 65% were sarcopenic, 72% myosteatotic, 52% VO and 20% had sarcopenic obesity (SO). VO patients were significantly less likely to have advanced T Stage (T3-4) OR0.62(95%CI 0.44–0.86, p = 0.005); nodal metastases OR0.60(95%CI 0.44–0.82, p = 0.001); vascular invasion OR0.63(95%CI 0.46–0.88, p = 0.006) and poor tumour differentiation OR0.49(95%CI 0.28–0.86, p = 0.012). Myosteatotic patients were more likely to have metastatic disease OR2.31(95%CI 1.15–4.63, p = 0.018) but less likely to have poorly differentiated tumours OR0.48(95%CI 0.27–0.86, p = 0.013). SO patients were significantly more likely to have poorly differentiated tumours OR2.01(95%CI 1.04–3.87, p = 0.037). ConclusionVO predisposes to earlier stage tumours with a less aggressive tumour phenotype. The SO group have adverse tumour characteristics which may be explained by differences in fat distribution. Myosteatosis relates to increased likelihood of distant metastasis that may be related to a systemic inflammatory response, despite the association with better differentiated tumours.

Altered features of body composition in older adults with type 2 diabetes and prediabetes compared with matched controls.

BackgroundAgeing is accompanied by muscle loss and fat gain, which may elevate the risk of type 2 diabetes (T2D). However, there is a paucity of data on the distribution of regional lean and fat tissue in older adults with T2D or prediabetes compared with healthy controls. The objective of this study was to compare regional body composition [by dual‐energy x‐ray absorptiometry (DXA)], muscle and subcutaneous adipose tissue (SAT) thicknesses (by ultrasound), and ultrasound‐based muscle texture features in older adults with T2D or prediabetes compared with normoglycaemic controls.MethodsEighteen adults > 60 years with T2D or prediabetes (T2D group) were individually matched to normoglycaemic participants [healthy matched (HM) group] for age (±5 years), sex, and body fat (±2.5%). In a single study visit, all participants received a whole‐body DXA scan and ultrasound assessment of the abdomen and anterior thigh. At these two landmarks, we used ultrasound to measure muscle and SAT thickness, as well as texture features of the rectus femoris and rectus abdominis. We also conducted an exploratory subanalysis on a subset of participants (n = 14/18 in the T2D group and n = 10/18 in the HM group) who underwent additional assessments including strength testing of the knee extensors (using a Biodex dynamometer), and a fasting blood sample for the measurement of circulating markers of glucose metabolism [glucose, insulin, c‐peptide, and the homoeostatic model assessment of insulin resistance (HOMA‐IR)].ResultsThe T2D group was 72 ± 8 years old (mean ± SD), predominantly male (n = 15/18; 83%), and overweight (BMI: 27.8 ± 4.2 kg/m2, 33.2 ± 5.3% body fat). DXA‐derived upper arm lean mass was 0.4 kg greater (P = 0.034), and leg fat mass was 1.4 kg lower (P = 0.048), in the T2D vs. HM group. Ultrasound‐based texture features were distinct between the groups [rectus abdominis blob size: 0.07 ± 0.06 vs. 0.30 ± 0.43 cm2, P = 0.045; rectus femoris local binary pattern (LBP) entropy: 4.65 ± 0.05 vs. 4.59 ± 0.08 A.U., P = 0.007]. When all participants who underwent additional assessments were pooled (n = 24), we observed that certain ultrasound‐based muscle texture features correlated significantly with muscle strength (rectus abdominis histogram skew vs. power during an isokinetic contraction at 60°/s: r = 0.601, P = 0.003) and insulin resistance (rectus femoris LBP entropy vs. HOMA‐IR: r = 0.419, P = 0.042).ConclusionsOur findings suggest a novel body composition phenotype specific to older adults with T2D or prediabetes. We are also the first to report that ultrasound‐based texture features correspond with functional outcomes. Future larger scale studies are needed to uncover the mechanisms underpinning these regional body composition differences.

Anti-CD47 antibody treatment attenuates liver inflammation and fibrosis in experimental non-alcoholic steatohepatitis models.

With the epidemic burden of obesity and metabolic diseases, nonalcoholic fatty liver disease (NAFLD) including steatohepatitis (NASH) has become the most common chronic liver disease in the western world. NASH may progress to cirrhosis and hepatocellular carcinoma. Currently, no treatment is available for NASH. Therefore, finding a therapy for NAFLD/NASH is in urgent need. Previously we have demonstrated that mice lacking CD47 or its ligand thrombospondin1 (TSP1) are protected from obesity-associated NALFD. This suggests that CD47 blockade might be a novel treatment for obesity-associated metabolic disease. Thus, in this study, the therapeutic potential of an anti-CD47 antibody in NAFLD progression was determined. Both diet-induced NASH mouse model and human NASH organoid model were utilized in this study. NASH was induced in mice by feeding with diet enriched with fat, fructose and cholesterol (AMLN diet) for 20weeks and then treated with anti-CD47 antibody or control IgG for 4weeks. Body weight, body composition and liver phenotype were analysed. We found that anti-CD47 antibody treatment did not affect mice body weight, fat mass or liver steatosis. However, liver immune cell infiltration, inflammation and fibrosis were significantly reduced by anti-CD47 antibody treatment. In vitro data further showed that CD47 blockade prevented hepatic stellate cell activation and NASH progression in a human NASH organoid model. Collectively, these data suggest that anti-CD47 antibody might be a new therapeutic option for obesity-associated NASH and liver fibrosis.

Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease.

An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the “sarcopenic NAFLD phenotype.” This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.

Composition of the body in male patients with rheumatoid arthritis with account of androgenic status

Aim. To evaluate alterations in body composition and bone mineral density (BMD) in male patients with rheumatoid arthritis (RA) taking into account their androgen status. Materials and methods. The single-stage study included 96 male RA patients. The mean age of patients was 59 [54; 64.75] years. The control group included 30 healthy men of comparable age. The androgen status assessment was based on sex hormone binding globulin (SHBG), total and free testosterone levels determination. Body composition and BMD measurements were performed using dual-energy X-ray absorptiometry (DXA) on the Stratos dR device (DMS, France) with the program “Whole Body”. Depending on the combination of BMD, lean- and fat-mass parameters, phenotypes of body composition were determined. The study was approved by Pirogov Russian National Research Medical University Local Ethics Committee. All patients signed informed consent.Results. Generally, lumbar spine, femoral neck and total hip BMD in RA patients was significantly less than in the control group (p<0.05). In 69 (71.9%) patients with RA osteopenic syndrome was detected. It was represented by osteopenia and osteoporosis (OP) in 60.4% and 11.5% of cases respectively. The spine and femoral neck BMD correlated negatively with SHBG level, and positive correlation was detected between BMD and free testosterone level. The RA patients had significantly less lean mass than the control group. Low lean mass was found in 48.9% of patients in the main group and was not detected in the control group. Appendicular lean mass (ALM) correlated positively with total and free testosterone levels. According to DXA data, the adipose tissue content (%) corresponded to obesity in 63.3% of patients. Adipose tissue indicators correlated negatively with SHBG, total and free testosterone levels. The BMD of various skeleton parts correlated positively with trunk lean mass, and the femoral neck and total hip BMD had positive relationships with body mass index (BMI). Body composition alterations were revealed in 93.2% of RA patients. The most common phenotypes were osteosarcopenic obesity (25%), osteopenic obesity (21.6%) and osteopenic sarcopenia (14.8%). Conclusion. Our study shows that RA course in men is associated with the development of osteopenic syndrome in 71.9% of cases and ALM decrease to diagnostic values of sarcopenia in 48.9% of cases. This fact should be considered in the development of a gender approach to RA patients management and rehabilitation.

Is craniofacial morphology and body composition related by common genes: Comparative analysis of two ethnically diverse populations.

The overarching hypothesis of the present paper is that ethnically and/or genetically diverse human populations may exhibit similarity in correlations between various aspects of human phenotypes due to the morphological integration process during the ontogenetic stages. To test this we investigated whether an association between craniofacial (CF) features and body composition (BC) variations is present in humans and the extent to which such possible associations are comparable in different populations. Furthermore, the paper examines the contribution of common genetic (additive) and shared familial environmental factors in assessing the correlation between CF and BC characteristics in humans. Two pedigree-based samples were collected from two distinct populations, including India (Santhal) and Europe (Chuvash). Canonical correlation analysis was used to compare the association between CF and BC characteristics in the two studied samples. The contribution of genetic and familial environmental factors on the correlation between CF and BC features was analyzed through variance decomposition analysis by implementing the Mendelian Analysis package (MAN). Our study suggests that CF morphology is significantly (p < 0.001) associated with BC variation in both samples. CF characteristics and BC phenotypes revealed a consistent trend in both samples where condensed and broad CF morphology was significantly associated with increased fat accumulation, with slight variations between the Santhal and Chuvash samples. Despite the variations observed between the samples, the heritability estimates were impressively equivalent for traits like total facial height (55.6%Santhal vs.56.1%Chuvash ) and nasal index (42.8%Santhal vs. 43.3%Chuvash ). The genetic contribution of CF morphology appeared to be extensive and the contribution of common genetic and shared family environmental correlations between CF and BC measures were suggestively substantial. Accordingly, these correlations were consistently observed across ethnically diverse populations, despite drastic morphological differences between the samples under comparison.

Determination of Peak Aerobic Capacity in Normal Weight Obesity and Metabolically Healthy Obesity

ObjectivesThe true cardiometabolic risk of the novel body composition phenotypes normal-weight obesity (NWO) and metabolically healthy obesity (MHO) remains controversial. Cardiorespiratory fitness, as measured by peak oxygen uptake during exercise (VO2peak), is inversely correlated with CVD and mortality. The objective of this project was to determine VO2peak in NWO and MHO relative to appropriate positive and negative control groups. MethodsFor this cross-sectional study, participants aged 18–50 years were recruited into one of four groups based on BMI, body composition, and metabolic risk factors: NWO (normal BMI with high body fat percentage (BF%)); MHO (obese BMI, high BF%, and up to one of the diagnostic criteria for metabolic syndrome (MetS) as defined by the International Diabetes Federation); MetS (obese BMI, high BF%, and at least three of the diagnostic criteria for MetS); and healthy controls (HC; normal BMI, BF%, and metabolic markers). Participants engaged in a maximal exercise test on a cycle ergometer to determine VO2peak and a DEXA scan to assess BF%. Data were analyzed using one-way ANOVA. ResultsA total of 35 participants completed this study (HC: n = 10; NWO: n = 8; MHO: n = 10; MetS: n = 7). VO2peak was greater in HC (44.2 ± 11.0 ml/kg/min) compared to NWO (28.6 ± 5.1 ml/kg/min; P = 0.002), MHO (25.4 ± 6.7 ml/kg/min; P < 0.0001) and MetS (24.3 ± 8.8 ml/kg/min; P = 0.0002). VO2peak was similar among NWO, MHO, and MetS (p’s ≥ 0.76). BF% was lower in HC (23.4 ± 5.5%) compared to NWO (32.6 ± 3.8%; P = 0.0099), MHO (41.9 ± 6.0%; P < 0.0001) and MetS (32.5 ± 6.1%; P = 0.016). BF% was also greater in MHO compared to NWO (P = 0.0085) and MetS (P = 0.0115). There was no significant difference in BF% between NWO and MetS (P > 0.9999). Across groups, there was a strong inverse correlation between BF% and VO2peak (r = –0.83). ConclusionsVO2peak did not significantly differ among all three at-risk groups (NWO, MHO, and MetS), and all were lower than HC. BF% also did not significantly differ between NWO and MetS groups, and BF% was actually greater in MHO compared to MetS and NWO. NWO and MHO, despite normal BMI and metabolic markers, respectively, have a VO2peak more similar to MetS than HC, suggesting increased cardiometabolic risk. Funding SourcesAmerican Society for Nutrition Mars. Inc Predoctoral Fellowship.

Does oxaliplatin pharmacokinetics (PKs) explain associations between body composition and chemotherapy toxicity risk in older adults with gastrointestinal (GI) cancers?

3095 Background: Considerable inter-individual variability in oxaliplatin toxicity exists in older adults with GI cancers. Low lean body mass (LBM), commonly known as sarcopenia, influences toxicity and is not incorporated in standard body surface area-based dosing, which may affect oxaliplatin PK and tolerability, but has not been examined systematically. Methods: We examined oxaliplatin PK in 26 older adults (103 concentrations) with GI cancers (NCT03998202). Using the transverse section at L3, skeletal muscle area (SMA) and total adipose tissue (TAT) were quantified (Slice-O-Matic software) and LBM was calculated (LBM = 0.30 × SMA + 6.06). Noncompartmental methods (WinNonlin 7.0) were used for PK estimates and a one compartment population PK model (PopPK) was developed. Covariates included age, sex, LBM, TAT, weight, BMI, creatinine clearance, BSA, serum albumin, and body composition phenotypes (i.e. low LBM-high TAT, etc.). Results: Median age was 68yrs, 69% male, 88% white, and mostly colorectal (62%) and pancreatic (27%) cancers. There was wide variability in oxaliplatin volume of distribution (Vd: 12.5-259L), peak concentrations (Cmax: 404-3642ng/mL), and clearance (CL: 26.7-270L/hr). Participants with lower LBM had lower Vd (r = 0.51, p&lt; 0.01); those with higher TAT had higher Cmax (r = 0.53, p&lt; 0.01). Higher albumin was associated with lower Cmax (r = -0.49, p= 0.01) and higher CL (r = 0.47, p= 0.01). The phenotype of low LBM + high TAT had the lowest Vd (Relative Risk [RR] 0.32, p= 0.01), lowest CL (RR 0.39, p&lt; 0.01), and highest Cmax (RR 3.3, 95% CI 1.7-6.5, p&lt; 0.01). Eleven patients (44%) had grade 3-5 chemotoxicity. Vd (r = -0.46, p= 0.02) and Cmax (r = 0.44, p= 0.03) were associated with grade 3-5 chemotoxicity. The phenotype of low LBM + high TAT was associated with a 45% higher risk of grade 3-5 chemotoxicity (RR = 1.45, 95% CI 1.1-2.1, p= 0.04), while BSA was not (r = -0.04, p= 0.9). In the popPK model, body composition was associated with PK (TAT with Vd [p = 0.006] and CL [p &lt; 0.001]), as was albumin (Vd p = 0.004; CL p = 0.002), while BSA was not (Vd p = 0.08; CL p = 0.2). Compared to BSA, an additional 11-17% in oxaliplatin PK variability was explained by LBM (11%), TAT (14%), and albumin (17%). Conclusions: Relationships between body composition, oxaliplatin PK, and severe chemotoxicity suggest the need for novel dosing strategies that incorporate body composition to reduce chemotoxicity and improve outcomes. Clinical trial information: NCT03998202.

New Frontiers of Body Composition in Sport.

The body composition phenotype of an athlete displays the complex interaction among genotype, physiological and metabolic demands of a sport, diet, and physical training. Observational studies dominate the literature and describe the sport-specific physique characteristics (size, shape, and composition) of adult athletes by gender and levels of competition. Limited data reveal how body composition measurements can benefit an athlete. Thus, the objective is to identify purposeful measurements of body composition, notably fat and lean muscle masses, and determine their impact on the health and performance of athletes. Areas of interest include relationships among total and regional body composition measurements, muscle function, sport-specific performance, risk of injury, return to sport after injury, and identification of activity-induced fluid shifts. Discussion includes the application of specific uses of dual X-ray absorptiometry and bioelectrical impedance including an emphasis on the need to minimize measurement errors and standardize protocols, and highlights opportunities for future research. This focus on functional body composition can benefit the health and optimize the performance of an athlete.

Cardiometabolic Profile of Different Body Composition Phenotypes in Children.

Cardiometabolic profiles of different body composition phenotypes are poorly characterized in young children, where it is well established that high adiposity is unfavorable, but the role of lean mass is unclear. We hypothesized that higher lean mass attenuates cardiometabolic risk in children with high fat mass. In 6-year-old children (n = 377) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective birth cohort, whole-body composition was measured by quantitative magnetic resonance, a novel validated technology. Based on fat mass index (FMI) and lean mass index (LMI), 4 body composition phenotypes were derived: low FMI-low LMI (LF-LL), low FMI-high LMI (LF-HL), high FMI-low LMI (HF-LL), high FMI-high LMI (HF-HL). Body mass index (BMI) z-score, fasting plasma glucose, insulin resistance, metabolic syndrome risk score, fatty liver index, and blood pressure. Compared with the LF-HL group, children in both high FMI groups had increased BMI z-score (HF-HL: 1.43 units 95% CI [1.11,1.76]; HF-LL: 0.61 units [0.25,0.96]) and metabolic syndrome risk score (HF-HL: 1.64 [0.77,2.50]; HF-LL: 1.28 [0.34,2.21]). The HF-HL group also had increased fatty liver index (1.15 [0.54,1.77]). Girls in HF-HL group had lower fasting plasma glucose (-0.29 mmol/L [-0.55,-0.04]) and diastolic blood pressure (-3.22 mmHg [-6.03,-0.41]) than girls in the HF-LL group. No similar associations were observed in boys. In a multi-ethnic Asian cohort, lean mass seemed to protect against some cardiometabolic risk markers linked with adiposity, but only in girls. The FMI seemed more important than lean mass index in relation to cardiometabolic profiles of young children.

Body composition and breast cancer risk and treatment: mechanisms and impact.

The purpose of this review is to clarify the association of body composition with breast cancer risk and treatment, including physiological mechanisms, and to elucidate strategies for overcoming unfavorable body composition changes that relate to breast cancer progression. We have summarized updated knowledge regarding the mechanism of the negative association of altered body composition with breast cancer risk and treatment. We also review strategies for reversing unfavorable body composition based on the latest clinical trial results. Body composition changes in patients with breast cancer typically occur during menopause or as a result of chemotherapy or endocrine therapy. Dysfunction of visceral adipose tissue (VAT) in the setting of obesity underlies insulin resistance and chronic inflammation, which can lead to breast cancer development and progression. Insulin resistance and chronic inflammation are also observed in patients with breast cancer who have sarcopenia or sarcopenic obesity. Nutritional support and a personalized exercise program are the fundamental interventions for reversing unfavorable body composition. Other interventions that have been explored in specific situations include metformin, testosterone, emerging agents that directly target the adipocyte microenvironment, and bariatric surgery. A better understanding of the biology of body composition phenotypes is key to determining the best intervention program for patients with breast cancer.

Body composition phenotypes in rheumatoid arthritis

Objective. To study body composition phenotypes, the frequency of osteoporosis (OP), sarcopenia (SP), and obesity in postmenopausal women with rheumatoid arthritis (RA). Material and methods. 99 women (aged 40-75 years) with RA were enrolled in the study. All patients were interviewed using a special questionnaire. Anthropometric measurements and muscle strength determination were also peiformed. Bone mineral density and body composition were assessed with dual energy X-ray absorptiometry. Results. The frequency of OP was 31.3 % and the confirmed SP was 21.2 %. Isolated osteopenic phenotype was found in 14.1 %, osteosarcopenia - in 6.1 %, isolated sarcopenic phenotype - in 2.0 %, and phenotypes with obesity (osteopenic obesity, osteosarcopenic obesity and isolated obesity) - in 70.7 % of patients. Only 7.1 % of women had healthy phenotype. Conclusion. Patients with RA had combined phenotypes of body composition more often than isolated ones. Phenotypes with obesity determined by densitometry were the most common.

Characterisation of body size phenotypes in a middle-aged Maltese population.

Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist-hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity - a cross-sectional study.

ObjectivesTo compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease.MethodsDetailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls.ResultsPsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (s.d. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (s.d. 1.83 l)] (P <0.001) and liver fat percentage [median 8.88% (interquartile range 4.42–13.18%)] compared with MDF controls [3.29% (1.98–7.25%)] (P <0.001). These differences remained significant after adjustment for age, sex and BMI. There were no statistically significant differences in VAT, liver fat or muscle fat infiltration (MFI) between PsA and type 2 diabetes. PsA participants had a lower thigh muscle volume than MDF controls and those with type 2 diabetes. Body composition-predicted propensity for CHD and type 2 diabetes was 1.27 and 1.83 times higher, respectively, for PsA compared with matched-MDF controls.ConclusionIndividuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk.

Obesity, Sarcopenia, and Outcomes in Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors.

Body composition refers to the proportional content of body fat mass and lean body mass that can lead to a continuum of different phenotypes ranging from cachectic/sarcopenic state to obesity. The heterogenetic phenotypes of body composition can contribute to formation of some cancer types and can sometimes lead to disparate outcomes. Both of these extremes of the spectrum exist in patients with non-small cell lung carcinoma (NSCLC). The discovery of new pathways that drive tumorigenesis contributing to cancer progression and resistance have expanded our understanding of cancer biology leading to development of new targeted therapies including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) that have changed the landscape of NSCLC treatment. However, in the new era of precision medicine, the impact of body composition phenotypes on treatment outcomes and survival is now being elucidated. In this review, we will discuss the emerging evidence of a link between body composition and outcomes in patients with NSCLC treated with TKI and ICI. We will also discuss suggested mechanisms by which body composition can impact tumor behavior and anti-tumor immunological response.

1560P Sarcopenia and sarcopenic obesity in pancreatic ductal adenocarcinoma (PDAC) patients undergoing surgery after neoadjuvant therapy (NAT): Prevalence and clinical implications

Body anthropometry may be markedly affected by NAT for PDAC. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher morbidity and mortality. The present study evaluated the impact of sarcopenia/sarcopenic obesity and changes in body composition (BC) following NAT on surgical and survival outcomes in patients (pts) undergoing surgery for PDAC. PDAC pts with available CT-scans (both at diagnosis and preoperatively) undergoing surgical resection after NAT at two academic medical institutions from 2013 to 2015 were retrospectively assessed. BC was estimated by analyzing axial L3 CT images before and after NAT. Data were correlated with overall survival (OS) using a Cox regression model. Kaplan-Meier curves were compared with Log-Rank test. The final cohort consisted of 108 pts, with a median age of 63 years and a median follow-up of 16 months. Ninety-one pts (89.8%) received FOLFIRINOX. Sarcopenia and sarcopenic obesity were found at diagnosis in 41.7% and 16.7% of pts, respectively. After NAT, all body compartments significantly changed (p < 0.001); the prevalence of sarcopenia and sarcopenic obesity decreased to 30.5% and 10.2%, respectively, after NAT. These BC phenotypes were associated with a higher overall complications rate after surgery (69.7% vs. 30.3%, p = 0.027 and 81.8% vs. 18.2% %, p = 0.048, respectively). Particularly, cardiac complications were related to sarcopenia (9% vs. 0%, p = 0.028) and pts that developed postoperative complications had higher preoperative total adipose tissue (300 vs. 229 cm2, p > 0.05). With regards to OS, sarcopenic obesity at baseline (HR 3.45, p = 0.023) was found to be a significant independent predictor for OS at multivariate analysis. Our data provide evidence that BC impacts on both surgical and survival outcomes in PDAC pts undergoing NAT before resection. The associations with worse clinical outcomes emphasize the role of a careful nutritional evaluation, as well as the need to develop appropriate evidence-based nutritional interventions during NAT.

Fat-Free Mass Is Better Related to Serum Uric Acid Than Metabolic Homeostasis in Prader-Willi Syndrome.

Background: Prader-Willi syndrome (PWS) is conventionally regarded as a model of genetic obesity carrying a metabolically healthier profile and fat compartmentalization than subjects with non-syndromic obesity. Serum uric acid (sUA) is a recognized surrogate marker of metabolic derangement. As no information is currently available on sUA levels in adults with PWS, we aimed to analyze sUA in a large cohort of adult patients with PWS in comparison to a control counterpart; secondly, we aimed to investigate the metabolic and non-metabolic determinants of sUA in PWS. Methods: A cross-sectional study was conducted on 89 consecutive adult patients with genetically confirmed PWS spanning a wide BMI range (17.2–56.7 kg/m2). As controls, 180 age-, sex- and BMI-matched healthy controls were included. sUA levels were analyzed in relation to the PWS status, metabolic variables, hormone status, body composition, and resting energy expenditure (REE). Bivariate correlation and multivariable regression studies were used to test for predictors of sUA in PWS. Results: Despite having similar BMI values, patients with PWS presented with higher FM (p < 0.0001), lower FFM (p < 0.0001) and REE values than controls (p < 0.0001). In PWS, sUA levels were non-significantly different between subjects with and without obesity (5.4 ± 1.3 vs. 4.9 ± 1.1 mg/dL, p = 0.09), and did not vary significantly in relation to genotype, sex steroid or GH replacement, as well as psychiatric treatments. Rates of hyperuricaemia (19.1% vs. 33.7%, p < 0.01) and absolute sUA levels were lower in patients with PWS compared to controls owing to significant differences between subgroups with obesity (5.5 ± 1.4 vs. 6.6 ± 1.6 mg/dL, p < 0.0001). In merged populations, sUA increased in parallel with age, BMI, FM, FFM, REE, glucolipid homeostasis, and inflammatory markers. In a separate analysis in PWS, however, sUA correlations with BMI, FM, and inflammatory markers were null. Stepwise multivariable regression analysis in the PWS group adjusted for karyotype, age, sex, FM, FFM, obesity, triglycerides, and HDL cholesterol, showed that sUA levels were independently associated with FFM (β = 0.35, p < 0.0001) and, albeit less significantly, with triglycerides (β = 0.23, p < 0.05). The introduction of height-normalized FFM (FFM index) in the regression model, however, abrogated the predictive role of FFM on sUA. Conclusions: FFM mass is a strong predictor of sUA. PWS is associated to lower sUA levels than controls likely due to genetic predisposition to different body composition and healthier metabolic phenotype. Further studies are warranted to assess purine metabolism and the clinical significance of the FFM index in PWS.

Myopenia and Reduced Subcutaneous Adiposity in Children With Liver Disease Are Associated With Adverse Outcomes.

Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications. This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm2 /height2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score <-2 and low SAT was defined as SAT index z-score <-1.5. Anthropometric, biochemical, and clinical data (hospitalization, complications, growth, neurodevelopment, energy/protein intake) were collected at LTx assessment, LTx, and post LTx (first hospitalization, 6 months, 12 months). Four distinct body composition phenotypes in children with ESLD were found: (1) myopenia with low SAT (17%;5 of 30), (2) myopenia (3%;1 of 30), (3) low SAT (20%;6 of 30), (4) normal muscle mass and SAT (60%;18 of 30). Myopenia with low SAT was prevalent in older (>2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal). Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important.

Physical activity and inactivity among different body composition phenotypes in individuals with moderate to very severe chronic obstructive pulmonary disease

BackgroundThe phenotype profiling of individuals with chronic obstructive pulmonary disease (COPD) according to impairments in body composition and level of physical activity in daily life (PADL) needs to be determined. ObjectiveTo verify if individuals with COPD classified as physically active/inactive present different characteristics within different body composition phenotypes. MethodsIndividuals with COPD were cross-sectionally stratified into four groups according to fat-free and fat mass indexes: Normal Body Composition (NBC), Obese (Ob), Sarcopenic (Sarc), and Sarcopenic/Obese (Sarc/Ob). Additionally, individuals had their PADL level objectively assessed through activity monitoring during two weekdays for at least 10h/day, and then were classified as physically active (Act) or inactive (Inact) according to international recommendations. Lung function (spirometry), exercise capacity (6-minute walking test [6MWT]) and peripheral muscle strength (1-repetition maximum [1RM]) were also assessed. Results176 individuals with COPD (mean±standard deviation age: 67±8 years, body mass index 26±6kg/m2, FEV1 47±16%predicted) were classified as: NBC+Act (17%), NBC+Inact (22%), Ob+Act (6%), Ob+Inact (10%), Sarc+Act (12%), Sarc+Inact (9%), Sarc/Ob+Act (8%) and Sarc/Ob+Inact (16%). The Sarc/Ob+Inact group presented lower 6MWT and 1RM for knee extension compared to NBC+Act, NBC+Inact, and Ob+Act groups (p<0.05). The Sarc/Ob+Inact group also presented lower FEV1% predicted, 1RM for elbow flexion and elbow extension compared to the NBC+Act and NBC+Inact groups and lower 1RM for elbow extension compared to Ob+Inact group (p<0.05). ConclusionThe combination of sarcopenia, obesity, and physical inactivity was shown to be detrimental in individuals with COPD. Therefore, this profile is a main therapeutic target for improving PADL level and/or body composition.

A significant association of non-obese non-alcoholic fatty liver disease with sarcopenic obesity

Non-alcoholic fatty liver disease (NAFLD) is significantly related to sarcopenia as well as obesity and its associated comorbidities. This cross-sectional study aims to examine the association between four body composition phenotypes (standard, obesity alone, sarcopenia alone, sarcopenic obesity) and non-obese NAFLD, or obese NAFLD. Reduced muscle mass and high percentage of body fat mass was measured by dual-energy x-ray absorptiometry, and body composition phenotypes were determined, according to Asian criteria for sarcopenia. Based on body mass index (BMI) cut-off point (25kg/m2) and hepatic steatosis on ultrasound, 748 subjects who underwent a health checkup were enrolled and divided into three groups: non-obese NAFLD, obese NAFLD, and no steatosis. Of 563 subjects (64.1±13.0 years) without secondary causes for steatosis, the overall prevalence of non-obese NAFLD and obese NAFLD were 17% and 16%, respectively. The former prevalence remained relatively constant at around 20% from the 50s to 80's, while the proportion of sarcopenic obesity in all subjects increased gradually with age, reaching 18% in the 80's. Multivariate analysis demonstrated a significant association between sarcopenic obesity and non-obese NAFLD after adjusting for confounders (odds ratio=2.367, 95% confidence interval=1.317-4.254, P=0.004). On the other hand, no significant association was found between obesity alone and obese NAFLD, when BMI and visceral adipose tissue were added as confounders, although 91% of obese NAFLD was included in obesity alone phenotype. Non-obese NAFLD had a significant association with sarcopenic obesity, independent of metabolic confounders. Early treatment intervention for non-obese NAFLD could suppress the deterioration of sarcopenic obesity because non-obese NAFLD might be a risk factor for sarcopenic obesity.