Body Composition Phenotypes Research Articles

Common Genetic Factors May Play a Role in the Relationships Between Body Composition, Adipokines, and Low-Back-Pain-Related Disability

In this study, we evaluated the contribution of the putative genetic factors into the established associations between selected circulating adipokine levels, body composition measurements, and low-back-pain-related disability scores (LBP_DS). A total of 1078 individuals from 98 nuclear families (with 1 to 11 siblings per family) were examined. A detailed self-report questionnaire was used to collect LBP disability data; body composition (fat, skeletal muscle mass, and extracellular water (ECW)) was assessed using the bioimpedance method; plasma levels of adipokines were measured by ELISA. Pedigree-based statistical analysis methods were used, including family-based variance component analysis (VCA) and principal phenotype analysis (PPA), to estimate the contribution of potential genetic and environmental factors. The VCA revealed a significant additive genetic component in LBP_DS and for the selected body composition phenotypes and adipokines. The study also revealed that both adipokines (GDF-15, chemerin, and follistatin) and body composition variables (BMI, fat mass/weight, waist circumference, and ECW) were genetically correlated with LBP_DS. Next, PPA generated two synthetic phenotypes: PPCT (combining cytokines) and PPBC (combining body composition variables). There was no significant correlation between the putative genetic factors underlying the created PPs. However, each of them displayed a significant genetic correlation with LBP_DS. These findings indicate that genetic factors that are assumingly common for several adipokine variations and several body composition measurements, respectively, presumably have a pleotropic genetic influence on the LBP_DS variation, independently from one another. This, in turn, suggests that the alleged genetic factors employing pleiotropic effects on LBP_DS have a complex and probably non-overlapping composition.

Clinically relevant body composition phenotypes are associated with distinct circulating cytokine and metabolomic milieus in epithelial ovarian cancer patients

Clinically relevant body composition phenotypes are associated with distinct circulating cytokine and metabolomic milieus in epithelial ovarian cancer patients

Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study.

While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC. A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model. Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69years (range 36-85), with a median follow-up of 12months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P<0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P=0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P<0.0001 and 30.7% vs. 73.2%, P<0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P<0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P=0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P=0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P<0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P<0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P<0.0001). Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers.

Dietary Patterns Associated with Body-Composition Phenotype in a Middle-Aged and Elderly Population: A Population-Based Cross-Sectional Study.

There is currently limited understanding of the intricate dynamics between fat and muscle mass and the potential effect of dietary patterns. This study aimed to investigate the effects of overall dietary patterns on four body composition phenotypes associated with central obesity and low muscle mass in the middle-aged and elderly population of Korea. We examined data from 6120 adults aged ≥ 50 years, collected during the 4th (2008-2009) and 5th (2010-2011) Korea National Health and Nutrition Examination Survey. Participants were classified into four groups according to their combined status of central obesity and low muscle mass: healthy control, central obesity, low muscle mass, and sarcopenic obesity. Using factor analysis on the twenty-two pre-defined food groups, we identified three distinct dietary patterns: the "Healthy dietary pattern", "Convenience-based dietary pattern", and "Alcohol and side dish pattern". Multivariate analysis included potential confounders such as age, sex, place of residence, marital status, educational level, occupation, household income, and physical activity level. Higher scores in the "Healthy dietary pattern" were associated with lower odds of sarcopenic obesity (OR = 0.61, 95% CI = 0.40-0.92, p for trend = 0.018). For the "Convenience-based dietary pattern", individuals in the third tertile of the dietary pattern score showed a marginal association with low muscle mass (OR = 1.18, 95% CI = 0.99-1.41, p for trend = 0.056). The "Alcohol and side dish pattern" was linked to higher odds of central obesity (OR = 1.22, 95% CI = 1.03-1.44, p for trend = 0.016) and low muscle mass (OR = 1.21, 95% CI = 1.01-1.45, p for trend = 0.043). The drinking practice of consuming foods high in saturated fats and salt alongside alcoholic drinks may negatively affect fat accumulation and muscle composition among older adults. Adopting a healthy eating pattern characterized by grains, vegetables, legumes, fruits, fish, and seaweed could be notably advantageous for promoting and maintaining healthy body composition and optimal skeletal muscle health.

Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant – results from a pilot study

BackgroundSarcopenia is common in end-stage liver disease and negatively impacts patients awaiting or undergoing liver transplantation (LT). Magnetic resonance imaging (MRI) may be used to measure body composition and sarcopenia. We aimed to evaluate the feasibility of MRI-based LT body composition profiling, describe waitlist body composition, and assess the natural rate of change in body composition while on the waitlist and post-LT.MethodsThis prospective pilot study recruited adults listed for LT at an urban, tertiary care facility. Eighteen participants were scanned at time of waitlisting and 15 had follow-up MRIs (waitlist and/or post-LT). An 8-min MRI was used to measure body composition (AMRA® Researcher) including thigh fat-free muscle volume (FFMV) and fat infiltration (MFI), visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volumes, and liver fat. A sex- and BMI invariant FFMV z-score (z-FFMV) was calculated, and muscle composition (MC) phenotypes were defined using the muscle assessment score (consisting of the FFMV z-score and sex-adjusted MFI). Rate of body composition change was calculated using mixed-effect modelling and is presented as rate per 30 days.ResultsAt time of waitlisting, 73% of the 18 participants had high MFI and 39% had the adverse MC (low FFMV z-score and high MFI) phenotype. Seven participants received an LT. Post-LT serial MRIs, at a median of 147 days apart within the first 200 days post-LT, demonstrated increased z-FFMV 0.22 SDs/(30 days) (p = 0.002), VAT 0.23 (p < 0.001), and ASAT 0.52 (p = 0.001) L/(30 days), but no change in MFI (p = 0.200) nor liver fat (p = 0.232).ConclusionMRI-based body composition profiling is feasible in LT patients and shortly after LT. This can be amended to routine clinical scans and may help in early identification of patients who may benefit from interventions to improve body composition. In addition, body composition changes significantly over time after LT.

Body compositions phenotypes of older adults with COPD.

Changes in nutritional status are important extrapulmonary manifestations of the chronic obstructive pulmonary disease (COPD). The study aimed to assess the prevalence of different body composition phenotypes in older patients with COPD and to investigate the relationship between these phenotypes and the severity of the disease, as well as physical performance of the subjects. The study included 124 subjects aged ≥60 with COPD. In all of them body composition analysis and muscle strength measurement were performed. Additionally, data from patients' medical records were analyzed. Study sample was divided into four groups based on the phenotypic body composition: normal phenotype (N), sarcopenia, obesity and sarcopenic obesity (SO). Incidence of sarcopenia was significantly higher in patients with severe or very severe COPD based on GOLD in comparison with subjects with mild or moderate obstruction (p = 0.043). Participants with sarcopenia, obesity and SO had lower results of the 6-min walk test than subjects with N (225.77 m, 275.33 m, 350.67 m, 403.56 m, respectively). Moreover, sarcopenia and SO had lower results than obesity (p = 0.001, p = 0.041, respectively). Sarcopenia is common in patients with advanced COPD. Sarcopenia and SO are associated with poorer physical performance. All older people with COPD should routinely have their body composition assessed, instead of simply measuring of body weight or body mass index (BMI).

Body composition phenotypes in the general population: the Austrian lead study

Body composition phenotypes in the general population: the Austrian lead study

The Association between Body Composition Phenotype and Insulin Resistance in Post-COVID-19 Syndrome Patients without Diabetes: A Cross-Sectional, Single-Center Study.

The most frequent body composition alterations in post-COVID-19 syndrome include low muscle mass, dynapenia, sarcopenia, and obesity. These conditions share interconnected pathophysiological mechanisms that exacerbate each other. The relationship between body composition phenotypes and metabolic abnormalities in post-COVID-19 syndrome remains unclear. To evaluate the association between body composition phenotypes and insulin resistance (IR) and metabolic abnormalities in non-diabetic individuals with post-COVID-19 syndrome. A cross-sectional, single-center study involving 483 subjects with post-COVID-19 syndrome following moderate to severe acute COVID-19 requiring hospitalization. Individuals with diabetes, those who declined to participate, or those who could not be contacted were excluded. Body composition phenotypes were classified as normal weight, dynapenia, sarcopenia, dynapenic obesity, and sarcopenic obesity (SO). The average age was 52.69 ± 14.75 years; of note, 67.08% were male. The prevalence of body composition phenotypes was as follows: 13.25% were of normal weight, 9.52% had dynapenia, 9.94% had sarcopenia, 43.69% had obesity, 18.84% had dynapenic obesity, and 4.76% had SO. Additionally, 58.18% had IR. Obesity (OR: 2.98, CI95%; 1.64-5.41) and dynapenic obesity (OR: 4.98, CI95%; 1.46-6.88) were associated with IR. The most common body composition phenotypes were obesity, dynapenic obesity, and dynapenia. Furthermore, obesity and dynapenic obesity were associated with IR in post-COVID-19 syndrome.

Association between body composition phenotypes and treatment toxicity in women with cervical cancer undergoing chemoradiotherapy

ObjectiveTo identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer. MethodsThis is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction. ResultsApproximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present. ConclusionsLower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). In this cohort study, patients (≥ 18years old) with CRC were followed for 36months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

Sarcopenia is independently associated with poor preoperative physical fitness in patients undergoing colorectal cancer surgery.

Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. Two hundred eighteen patients with stage I-III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2mL/kg/min (IQR 10.6-14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8mL/kg/min (IQR 15.4-23). On univariate linear regression analysis, male sex (P<0.001) was positively associated with VO2 at AT. While ASA grade (P<0.001) and BMI (P=0.007) were negatively associated with VO2 at AT, on multivariate linear regression analysis, these variables remained significant (P<0.05). On univariate linear regression analysis, male sex (P<0.001) was positively associated with VO2 peak, whereas age (P<0.001), ASA grade (P<0.001), BMI (P=0.003), sarcopenia (P=0.015), and myosteatosis (P<0.001) were negatively associated with VO2 peak. On multivariate linear regression analysis age (P<0.001), ASA grade (P<0.001), BMI (P<0.001), and sarcopenia (P=0.006) were independently and negatively associated with VO2 peak. The novel finding that sarcopenia is independently associated with reduced VO2 peak performance in CPET supports the supposition that reduced muscle mass relates to poor physical function in CRC patients. Further work should be undertaken to assess whether sarcopenia diagnosed on CT can act as suitable surrogate for CPET to further enhance personalized risk stratification.

Impact of high fat and low lean mass phenotype on bone mineral content: A cross-sectional study of Chinese adolescent population

Background and ObjectiveResearch on body composition phenotypes and bone health in adolescents is limited. Hence, this study aimed to analyze the relationship between different body composition phenotypes, bone mineral content, and bone metabolism markers in Chinese adolescents. MethodsIn this cross-sectional study, 1852 adolescents aged 12 to 18 years were selected from six schools in Yinchuan City between 2017 and 2020 using stratified cluster random sampling. The participant's body composition and bone mineral content (BMC) were measured using bioelectrical impedance analysis (BIA). Serum bone metabolic markers (OC, CTX, and Ca) were measured. Based on their FMI and LMI, individuals were categorized into four body composition phenotypes: low fat mass-low lean mass (LFMI-LLMI), low fat mass-high lean mass (LFMI-HLMI), high fat mass-high lean mass (HFMI-HLMI), high fat mass-low lean mass (HFMI-LLMI). ResultsThere was a statistically significant difference between the four different body composition phenotypes with BMC, CTX and Ca in boys (all P < 0.05), similar conclusions were found in girls, except the OC and CTX. After adjusting for age, gender, smoking, drinking, and others, compared with the LFMI-HLMI reference group, the two high FMI groups (HFMI-LLMI and HFMI-HLMI) had a greater negative correlation with BMC, while the low BMC risk of the HFMI-LLMI group was the highest (OR = 33.28; 95%CI: 11.12–99.63; P < 0.001). The correlation between BMC of different body composition phenotypes in boys was greater than that in girls. HFMI-HLMI is a risk phenotype negatively associated with Ca content (β = −0.12; 95%CI: −0.19 to −0.04; P < 0.05). Regardless of body composition level, BMC was always negatively correlated with fat mass (LLMI: β = −0.27; 95%CI: −0.32–0.21; HLMI: β = −0.52, 95%CI: −0.65–0.40) and positively correlated with lean mass (LFMI: β =0.24; 95%CI: 0.20–0.28; HFMI: β =0.23, 95%CI:0.13–0.33) (all P < 0.001). The fat mass showed different correlations with OC and CTX in girls and boys based on LLMI or HLMI (all P < 0.05). ConclusionHFMI-LLMI is a risk phenotype of low BMC in Chinese adolescents, and the relationship between fat mass and bone metabolism markers is affected by lean body mass and gender.

Osteosarcopenia in women with rheumatoid arthritis: association with nutritional status and physical condition

Objective: to evaluate nutritional status, muscle strength, functional status of skeletal muscles and physical activity (PHA) and their relationship with the osteopenic body composition phenotype in women in post menopause with rheumatoid arthritis (RA). Material and methods. The case-control study included 134 women in post menopause with RA, 52 of them had osteosarcopenia (OSP) according to densitometry and 82 had no decrease in bone mineral density (BMD) and muscle mass (mean age 62.0 ± 7.2 and 59.6 ± 7.5 years, respectively; p &gt; 0.05). A clinical and laboratory examination as well as tests to assess muscle strength and functional status were performed. The MNA-SF and IPAQ questionnaires were used to determine nutritional status and physical activity. Results and discussion. Malnutrition was found in 51.9 % of patients, and low and average levels of PHA were found in 5.8 and 50.0 % of patients with OSP, respectively. Factors associated with OSP were identified: nutritional status according to MNA-SF &lt; 12 points (odds ratio, OR 2.52; 95 % confidence interval, CI 1.10–5.77; p = 0.029), dietary calcium intake &lt; 500 mg/day (OR 3.23; 95 % CI 1.49–7.01; p = 0.003), 25(OH)D level &lt; 30 ng/ml (OR 4.55; 95 % CI 1.86–11.16; p = 0.001), moderate PHA &lt; 1 hour per day (OR 2.67; 95 % CI 1.06–6.75; p = 0.037), walking &lt; 1 hour per day and &lt; 4 hours per week (OR 3.25; 95 % CI 1.26–8.38; p = 0.015 and OR 3.17; 95 % CI 1.19–8.46; p = 0.021, respectively). Conclusion. Reduced nutritional status was found in 51.9 % and average or low levels of PHA in 55.8 % of patients with OSP. The risk of OSP development was increased by low nutritional status, inadequate dietary calcium intake, low vitamin D levels, short duration of daily moderate exercise, and inadequate daily and weekly walking time.

Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the fat mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality.

The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50). Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors.

Prognostic value of body composition in patients with digestive tract cancers: A prospective cohort study of 8,267 adults from China

The characterization and prognostic value of body composition parameter/phenotype based on computed tomography (CT) in patients with digestive tract cancers remain incomplete. This study aimed to investigate the relationship between parameter/phenotype and clinical outcomes in patients with digestive tract cancers. In this prospective cohort study, 8267 patients with digestive tract cancers were assessed using CT scans to determine body composition. Body composition data, including areas of skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), were collected at the third lumbar level on CT images obtained within 30 days before surgery. Body composition phenotypes (sarcopenia, cancer cachexia, sarcopenic obesity) were determined based on SM, SAT, and VAT areas. The primary endpoint was overall survival, obtained from electronic medical records and telephone follow-up surveys. Kaplan-Meier and log-rank analyses were employed to compare unadjusted survival, while multivariate survival analyses were conducted using a proportional hazards model adjusted for age, gender, and cancer-node-metastasis (TNM) stages. Adjusted hazard ratios (HRs) for all-cause mortality were calculated for the second (Q2), third (Q3), and fourth (Q4) quantiles relative to the first quantile (Q1) for SM areas, revealing adjusted summary HRs of 0.575 (95% CI, 0.361-0.916), 0.419 (95% CI, 0.241-0.729), and 0.384 (95% CI, 0.203-0.726), respectively. Sarcopenia-adjusted summary HRs were 1.795 (95% CI: 1.012-3.181) for male patients and 1.925 (95% CI: 1.065-3.478) for female patients. Cancer cachexia-adjusted summary HRs were 1.542 (95% CI: 1.023-2.324) for male patients and 1.569 (95% CI: 0.820-3.001) for female patients. Sarcopenic obesity-adjusted summary HRs were 1.122 (95% CI: 0.759-1.657) for male patients and 1.303 (95% CI: 0.623-2.725) for female patients. Subgroup analyses indicated varying prognostic values of body composition parameter/phenotype among different cancer types. Our findings suggest a large SM area is a favorable prognostic indicator, while cancer cachexia and sarcopenia signify poor prognosis in patients with digestive tract cancers. These findings have important implications for the personalized preoperative assessment of body composition in patients with digestive tract cancers.

Colostrum Supplementation to Rescue Antibiotic-Induced Dysbiosis and Reduce Long-Term Obesity Risk

The prevalence of metabolic disease in the United States has increased from 30.4% to 41.9% in the past decades, with rising rates among children. Emerging evidence implicates intestinal microbiome function as contributing to metabolic disease risk, with dysbiosis being associated with overweight and obese status. While sometimes lifesaving, antibioticssuch as azithromycin cause microbiota ecological instability and are significantly associated with a greater risk ofmetabolic disease and obesity in children. Since antibiotics are often necessary, the identification of nutritional interventions to restore microbial membership and function has a high potential value for millions of patients. Colostrum is the first milk produced by mammals immediately after birth and shapes intestinal colonization patterns, specifically enriching Bifidobacterium, Lactobacillus, and limiting the colonization of Proteobacteria. Bovine colostrum containsimmunomodulators, lactoferrin, oligosaccharides, bioactive compounds, and macronutrients. The compounds are similar across mammalian species. Considering the impact of colostrum in the sterile early-life gut, we hypothesized that bovine colostrum provided as a supplemental nutraceutical therapy would augment gut microbial recolonization following antibiotic exposures and mitigate long-term metabolic consequences. Specific pathogen-free (SPF) C57BL/6 mice (male, three weeks old, Jackson Laboratory) were housed under standard laboratory conditions with a 45% high-fat diet. Tylosintartrate antibiotic (ABX) was administered to some mice in drinking water 3 days/week over three weeks, with four days washout/week. To examine colostrum, some animals were provided colostrum gavage during or immediately following ABX exposures. After intervention, body composition and metabolic phenotypes were monitored for 16 weeks.Compared with ABX alone, colostrum following ABX maintained similar body composition and glucose tolerance as controls, while colostrum during ABX appeared similar to ABX alone. Examination of the gut microbiome showed unique enrichment of Akkermansia and Sutterella with decreased Enterobacteriaceae in mice treated with ABX followed by colostrum. Analysis of the gut mucosa demonstrated ABX decreased goblet cell numbers per villi (7.2/villus) compared with control (9.8/villus), and colostrum following ABX elevated goblet cells (8.6/villus). These data suggest colostrum may stimulate epithelial responses that foster host-microbial symbiosis at the mucosal surface and play a role in intestinal recolonization to benefit long-term homeostasis. Dairy Innovation Hub, UW-Madison. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Body Composition, Sarcopenic Obesity, and Cognitive Function in Older Adults: Findings From the National Health and Nutrition Examination Survey (NHANES) 1999–2002 and 2011–2014

Objective Sarcopenic-obesity (SO) is characterized by the concomitant presence of low muscle mass and high adiposity. This study explores the association of body composition and SO phenotypes with cognitive function in older adults. Methods Cross-sectional data in older adults (≥60 years) from NHANES 1999–2002 and 2011–2014 were used. In the 1999–2002 cohort, phenotypes were derived from body mass index (BMI) and dual-X-ray-absorptiometry, and cognition was assessed the by Digit-Symbol-Substitution-Test (DSST). In the 2011–2014 cohort, phenotypes were derived from BMI, waist-circumference (WC), and hand-grip-strength (HGS). Cognition was assessed using four tests: DSST, Animal Fluency, the Consortium-to-Establish-a-Registry-for-Alzheimer’s-Disease-Delayed-Recall, and Word Learning. Mediation analysis was conducted to evaluate the contribution of inflammation (C-reactive-protein, CRP) and insulin resistance (Homeostatic-Model-Assessment-for-Insulin-Resistance, HOMA-IR) to the association between body composition and cognitive outcomes. Results The SO phenotype had the lowest DSST mean scores (p < 0.05) and was associated with a significant risk of cognitive impairment [Odds Ratio (OR) = 1.9; 95%CI 1.0–3.7, p = 0.027] in the 1999–2002 cohort. A higher ratio of fat mass and fat free mass (FM/FFM) also showed a greater risk of cognitive impairment (OR = 2.0; 95%CI 1.3–3.1, p = 0.004). In the 2011–2014 cohort, the high WC-Low HGS group showed significantly lower scores on all four cognitive tests (p < 0.05) and a higher risk of cognitive impairment. CRP and HOMA-IR were significant partial mediators of the association between FM/FFM and DSST in the 1999–2002 cohort. Conclusions The SO phenotype was associated with a higher risk of cognitive impairment in older adults. Insulin resistance and inflammation may represent key mechanisms linking SO to the development of cognitive impairment.

Abstract 3403: Disentangling the obesity paradox in high-grade serous epithelial ovarian cancer

Abstract Background: Previously published evidence suggests an 'obesity paradox' in epithelial ovarian cancer, where excess adiposity is linked to better survival. However, prior studies did not jointly consider skeletal muscle, a key prognostic factor in cancer. Addressing this gap, our study examines the combined effects of adiposity and muscle phenotypes on mortality in high-grade serous epithelial ovarian cancer (HGSOC), offering novel insights into the role of body composition in patient outcomes. Methods: 343 HGSOC patients from the Body Composition and Epithelial Ovarian Cancer (BComES) Cohort at Roswell Park were included in this analysis. Body composition was derived from sliceOmatic software using computed tomography images obtained prior to chemotherapy. Body composition was quantified as surface area (cm2) at L3 for intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), and skeletal muscle index (SMI). SMI&amp;lt;38.5 cm2/m2 was defined as low SMI, a proxy for sarcopenia. For each adipose depot, phenotypes were categorized as: 1) low adiposity/high SMI (optimal/referent); 2) high adiposity/high SMI; 3) high adiposity/low SMI (e.g., sarcopenic obesity); and 4) low adiposity/low SMI (e.g., cancer cachexia). Multivariable Cox models adjusted for age, tumor stage, and surgical debulking status were used to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) representing associations of each body composition phenotype with mortality. Results: High IMAT and VAT were associated with increased mortality in patients with high SMI (HR=1.80, 95% CI: 1.18-2.74 and HR=1.96, 95% CI: 1.27-3.04, respectively) and low SMI (HR=1.65, 95% CI: 1.05-2.61 and HR=1.70, 95% CI: 1.04-2.80). High SAT and TAT were also associated with increased mortality in patients with high SMI (HR=1.74, 95% CI: 1.14-2.67 and HR=2.04, 95% CI: 1.31-3.18), but associations were shy of significance for patients with low SMI (HR=1.37, 95% CI: 0.85-2.23 and HR=1.58, 95% CI: 0.95-2.61). Lastly, low SMI and low adiposity was associated with increased mortality for VAT (HR= 1.65, 95% CI: 1.01-2.70), SAT (HR=1.88, 95% CI: 1.14-3.10), TAT (HR=1.97, 95% CI:1.19-3.26) and IMAT (HR=1.46, 95% CI: 0.85-2.53). Conclusions: In this study, we observed no support for an obesity paradox. Rather, we observed compelling evidence linking high adiposity phenotypes with striking increases in HGSOC mortality, regardless of SMI. Notably, as the cachectic phenotype was also linked to substantial increases in mortality, unwittingly assigning patients with low adiposity and low muscle to a reference group in adiposity research could falsely induce an ‘obesity paradox’. Importantly, as body composition can be modified through diet and exercise, our data establishes it as a potential therapeutic target alongside chemotherapy to improve outcomes in this deadly disease. Citation Format: Evan W. Davis, Nancy Barone, Charles Roche, Gyorgy Paragh, André Klein, Rikki Cannioto. Disentangling the obesity paradox in high-grade serous epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3403.

Abstract P187: Associations of Body Composition, Inflammation, and Lipids: The Multi-Ethnic Study of Atherosclerosis

Background: Prior evidence has linked inflammation with myopenic obesity (MO), a high cardiometabolic risk body composition phenotype characterized by low muscle and high fat mass. Inflammation may also alter lipid metabolism. This study aimed to examine the association between MO and lipids and whether inflammation is one potential mediator of their complex relationship. Methods: We conducted a cross-sectional analysis of 1,421 Multi-Ethnic Study of Atherosclerosis participants with abdominal computed tomography body composition, lipid, and inflammatory marker measurements. The ratio of total skeletal muscle area to total adipose tissue area (SM/AT) at L3-4 was used to identify MO (lowest sex-stratified tertiles of &lt;0.52 in men and &lt;0.44 in women). Principal component analysis was used to reduce six inflammatory markers by patterns of covariation. Parallel mediation analysis was conducted to examine whether the inflammatory components mediated the relationship between SM/AT and lipids, acknowledging the limitations of cross-sectional data. Results: The sample’s mean age was 64±10 years, 52.4% were female, and 42.1% were Caucasian. Participants with MO (n=474), compared to those without (n=947), had lower high-density lipoprotein cholesterol (HDL-C; 49±13 vs. 54±16, p&lt;0.001), higher remnant cholesterol (RC; 28±13 vs. 24±13, p&lt;0.001), and similar low-density lipoprotein cholesterol (LDL-C; 110±32 vs. 113±30, p=0.073). All inflammatory markers were higher in MO (p≤0.002). Parallel mediation analysis showed significant direct effects between SM/AT and both HDL-C and RC, which were mediated by component 1 but not component 2. There was no significant direct or indirect effect between SM/AT and LDL-C (Table 1). Conclusion: Participants with MO exhibited elevated levels of inflammation and unfavorable lipid profiles. Two inflammatory components were identified, one of which (IL-6, CRP, fibrinogen, and leptin) partially mediated the relationship of SM/AT with HDL-C and RC.