Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Patients With Inflammatory Bowel Diseases and Higher Visceral Adipose Tissue Burden May Benefit From Higher Infliximab Concentrations to Achieve Remission.

INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per µg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.

Every Day Counts: a randomized pilot lifestyle intervention for women with metastatic breast cancer.

PURPOSE: To explore the feasibility, adherence, safety and potential efficacy of Every Day Counts; a randomized pilot trial designed for women with metastatic breast cancer (MBC) framed by the American Cancer Society nutrition and physical activity (PA) guidelines METHODS: Women with clinically stable MBC were recruited to complete an interview, dual energy X-ray absorptiometry imaging and phlebotomy at baseline and post-intervention. Multidimensional quality of life, symptom burden, lifestyle behaviors (nutrition and PA) and biomarkers of prognosis were procured and quantified. Women were randomized to the immediate intervention or a waitlist control arm. The 12-week intervention included a curriculum binder, lifestyle coaching (in-person and telephone-based sessions) and intervention support (activity monitor, text messaging, cooking classes.) Women in the waitlist control were provided monthly text messaging. RESULTS: Forty women were recruited within 9 months (feasibility). Women in the immediate intervention attended 86% of all 12 weekly coaching sessions (adherence) and showed significant improvements in general QOL (p = 0.001), and QOL related to breast cancer (p = 0.001), endocrine symptoms (p = 0.002) and fatigue (p = 0.037), whereas the waitlist control did not (all p values ≥ 0.05) (efficacy). PA significantly increased for women in the intervention compared to control (p < 0.0001), while dietary changes were less evident across groups due to high baseline adherence. No significant changes in biomarkers or lean mass were noted, yet visceral adipose tissue declined (p = 0.001). No intervention-related injuries were reported (safety). Qualitative feedback strongly supports the desire for a longer intervention with additional support. CONCLUSIONS: Lifestyle interventions are of interest, safe and potentially beneficial for women with MBC. A larger trial is warranted.

Consumption of non-nutritive sweeteners during pregnancy.

In an effort to reduce sugar consumption to prevent diabetes mellitus and cardiovascular diseases, "sugar-free" or "no added sugar" products that substitute sugar with non-nutritive sweeteners (NNSs) (eg, Splenda, Sweet'N Low, and Stevia) have become increasingly popular. The use of these products during pregnancy has also increased, with approximately 30% of pregnant women reporting intentional NNS consumption. In clinical studies with nonpregnant participants and animal models, NNSs were shown to alter gut hormonal secretion, glucose absorption, appetite, kidney function, in vitro insulin secretion, adipogenesis, and microbiome dysbiosis of gut bacteria. In pregnant animal models, NNS consumption has been associated with altered sweet taste preference later in life and metabolic dysregulations in the offspring (eg, elevated body mass index, increased risk of obesity, microbiome dysbiosis, and abnormal liver function tests). Despite the accumulating evidence, no specific guidelines for NNS consumption are available for pregnant women. Furthermore, there are limited clinical studies on the effects of NNS consumption during pregnancy and postpartum and long-term outcomes in the offspring.

Body Mass Index and Gut Microbiome: A Cluster-Randomized, Controlled, Pilot Feasibility Study.

Background: Prebiotic fiber has been examined as a way to foster gut bacteria less associated with obesity. Tests of prebiotic fiber in reducing obesity have been conducted mainly in animals, adults, and Caucasians when the highest obesity rates are in African American and Latinx youth. Response to prebiotic fiber is determined by the pre-existing intestinal microbiota. The type of microbiota varies based on diet and physical activity (PA), so it is important to examine acceptability and response to prebiotic fiber in those most at risk for obesity. Methods: This cluster-randomized, controlled feasibility trial included an online program designed to improve diet and PA along with administration of a prebiotic fiber for 12 weeks in 123 students of 4th and 5th grade where 98% were eligible for free or reduced-fee lunch. Of these 56% were male; 71% Latinx; 15% African American; and 14% other. Results: Decrease in body fat (BF) was associated with higher pretest BF. Lower body mass index (BMI) was associated with decrease in fecal Tenericutes and increase in Actinobacteria. Conclusions: Prebiotic fiber can be helpful in supporting healthy weight, so inclusion in culturally congruent foods usually eaten by children from groups at high risk for obesity should be considered following additional studies. Determining those most responsive to prebiotic fibers can also permit individual recommendations for greater inclusion in usual diet choices. Clinical Trial Registration Number NCT05671731.

Energy expenditure and weight-related behaviors in youth with Down syndrome: a protocol.

Background: The consequences of obesity are ominous, yet healthcare professionals are not adequately preventing or treating obesity in youth with Down syndrome (DS). Total daily energy expenditure (TDEE) is the energy expended in 24 h through physical activity and life-sustaining physiologic processes. An individual's TDEE is essential for determining the daily caloric intake needed to maintain or change body weight. Successful prevention and treatment of obesity in youth with DS is severely compromised by the lack of data on TDEE and information on weight-related behaviors for this high-risk population. This manuscript describes the protocol for the federally funded study that is in process to determine daily energy expenditure in a large cohort of children with DS. Methods: This observational cross-sectional study will include a national sample of 230 youth with DS, stratified by age (5-11 and 12-18 years of age) and sex. Doubly Labeled Water analysis will provide the criterion body fat%, fat-free mass, and TDEE. To increase accessibility and decrease the burden on participants, the entire study, including obtaining consent and data collection, is conducted virtually within the participant's home environment on weekdays and weekends. The study team supervises all data collection via a video conferencing platform, e.g., Zoom. This study will (1) examine and determine average TDEE based on age and sex, (2) develop a prediction equation based on measured TDEE to predict energy requirements with a best-fit model based on fat-free mass, sex, age, and height and/or weight, and (3) use 24-hour dietary recalls, a nutrition and physical activity screener, wearable devices, and sleep questionnaire to describe the patterns and quality of dietary intake, sleep, and physical activity status in youth with DS. Discussion: The lack of accurate information on energy expenditure and weight-related behaviors in youth with DS significantly impedes the successful prevention and treatment of obesity for this vulnerable population. The findings of this study will provide a further understanding of weight-related behaviors as obesity risk factors, currently not well understood for this population. This study will advance the science of weight management in individuals with disabilities and shift clinical practice paradigms.

Quality of Dietary Intake in Children With Developmental Disabilities: A Pilot Study.

BACKGROUND: Children with developmental disabilities have a high prevalence of overweight and obesity. The role and contribution of their diet to weight status is poorly understood. OBJECTIVES: This pilot study describes the dietary quality of children with spina bifida and Down syndrome compared with typically developing peers. METHODS: Dietary intakes of 8 children with spina bifida or Down syndrome and 4 children without developmental disabilities, aged 8 to 18 years, were collected using six 24-hour dietary recalls through Facetime. Dietary quality was assessed by application of the Healthy Eating Index (HEI). RESULTS: Children with spina bifida and Down syndrome had higher HEI scores when compared to typically developing peers (48.3, 52.9, and 46.2, respectively) and vegetable consumption (1.9, 2.6, and 1.4, respectively). All groups had undesirable intakes of saturated fat, added sugar, and sodium. Within this small sample, children with spina bifida and Down Syndrome had similar diet quality to their typically developing peers. CONCLUSIONS: Further investigation in a larger sample is recommended to support the development of methods to optimize weight management in children with developmental disabilities.

Accuracy of body mass index in categorizing weight status in children with intellectual and developmental disabilities.

PURPOSE: To identify the accuracy of Body Mass Index (BMI) to categorize body weight in a sample of children with spina bifida and Down syndrome as compared to typically developing peers. METHODS: A secondary analysis of 32 children with spina bifida, Down syndrome or no chronic illness. A calculated BMI was plotted on the Centers for Disease Control and Prevention age- and sex-specific BMI growth charts to determine each child's weight status. Percentage of body fat, obtained by labeled water, was plotted on two different body fat percentile reference curves, one derived from a whole body measure (DXA) of body fat and one by skin-fold measure. Differences in weight categories between calculated BMI and body fat percentile curves were reported. RESULTS: The calculated BMI for children with a disability had significant misclassifications as a screening tool for body fat when compared to children without a disability. Misclassifications were increased with the body fat percentile reference curve derived from skin-fold measures and for children who primarily used a wheelchair. CONCLUSION: The current recommendation to use BMI to categorize weight status is not useful for many children with disabilities. Further research to identify an alternative pragmatic strategy is necessary.

Dietary Sodium Restriction Results in Tissue-Specific Changes in DNA Methylation in Humans.

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Do we need race-specific resting metabolic rate prediction equations?

BACKGROUND: Resting metabolic rate (RMR) is a key determinant of daily caloric needs. Respirometry, a form of indirect calorimetry (IC), is considered one of the most accurate methods to measure RMR in clinical and research settings. It is impractical to measure RMR by IC in routine clinical practice; therefore, several formulas are used to predict RMR. In this study, we sought to determine the accuracy of these formulas in determining RMR and assess additional factors that may determine RMR. METHODS: We measured RMR in 114 subjects (67% female, 30% African American [AA]) using IC. Along with standard anthropometrics, dual-energy X-ray absorptiometry was used to obtain fat-free mass(FFM) and total fat mass. Measured RMR (mRMR) by respirometry was compared with predicted RMR (pRMR) generated by Mifflin-St.Joer, Cunningham, and Harris-Benedict (HB) equations. Linear regression models were used to determine factors affecting mRMR. RESULTS: Mean age, BMI, and mRMR of subjects were 46 ± 16 years (mean ± SD), 35 ± 10 kg/m2, and 1658 ± 391 kcal/day, respectively. After adjusting for age, gender, and anthropometrics, the two largest predictors of mRMR were race (p < 0.0001) and FFM (p < 0.0001). For every kg increase in FFM, RMR increased by 28 kcal/day (p < 0.0001). AA race was associated with 144 kcal/day (p < 0.0001) decrease in mRMR. The impact of race on mRMR was mitigated by adding in truncal FFM to the model. When using only clinically measured variables to predict mRMR, we found race, hip circumference, age, gender, and weight to be significant predictors of mRMR (p < 0.005). Mifflin-St.Joer and HB equations that use just age, gender, height, and weight overestimated kcal expenditure in AA by 138 ± 148 and 242 ± 164 (p < 0.0001), respectively. CONCLUSION: We found that formulas utilizing height, weight, gender, and age systematically overestimate mRMR and hence predict higher calorie needs among AA. The lower mRMR in AA could be related to truncal fat-free mass representing the activity of metabolically active intraabdominal organs.

Feasibility and Acceptability of a Self-Report Activity Diary in Families of Children With and Without Special Needs.

This study was conducted to examine the feasibility and acceptability of a self-report activity diary completed by parents and older children to assess the child's daily activity in children with and without special needs. The study included 36 child/parent dyads stratified by child age and diagnosis. Parents (n = 36) and children ≥13 years (n = 12) were asked to report on the child's daily activity using an activity diary. Feasibility was determined based on successfully returned diaries and acceptability via post-study interview. Activity diaries were submitted by 94% of the parents and 100% of the children, with 83% and 80%, respectively, successfully completed. Comments provided post-study regarding the diaries were primarily on the format and were generally negative. The activity diary was feasible to use, but not well accepted within our sample of children with and without special needs or their parents. Further research is needed to create valid physical activity assessment measures that are population specific for individuals with special needs.

Technology-Based Dietary Assessment in Youth with and Without Developmental Disabilities.

Obesity prevalence is higher in children with developmental disabilities as compared to their typically developing peers. Research on dietary intake assessment methods in this vulnerable population is lacking. The objectives of this study were to assess the feasibility, acceptability, and compare the nutrient intakes of two technology-based dietary assessment methods in children with-and-without developmental disabilities. This cross-sectional feasibility study was an added aim to a larger pilot study. Children (n = 12; 8⁻18 years) diagnosed with spina bifida, Down syndrome, or without disability were recruited from the larger study sample, stratified by diagnosis. Participants were asked to complete six days of a mobile food record (mFR™), a 24-h dietary recall via FaceTime® (24 HR-FT), and a post-study survey. Analysis included descriptive statistics for survey results and a paired samples t-test for nutrient intakes. All participants successfully completed six days of dietary assessment using both methods and acceptability was high. Energy (kcal) and protein (g) intake was significantly higher for the mFR™ as compared to the 24 HR-FT (p = 0.041; p = 0.014, respectively). Each method had strengths and weaknesses. The two technology-based dietary assessment tools were well accepted and when combined could increase accuracy of self-reported dietary assessment in children with-and-without disability.

Total energy expenditure and body composition of children with developmental disabilities.

BACKGROUND: Obesity prevalence is increased in children with developmental disabilities, specifically in children with spina bifida and Down syndrome. Energy expenditure, a critical aspect of weight management, has been extensively studied in the typically developing population, but not adequately studied in children with developmental disabilities. OBJECTIVE: Determine energy expenditure, fat-free mass and body fat percentile and the impact of these findings on recommended caloric intake in children with spina bifida and Down syndrome. METHODS/MEASURES: This pilot study included 36 children, 18 with spina bifida, 9 with Down syndrome and 9 typically developing children. Half of the children with spina bifida were non-ambulatory. Doubly labeled water was used to measure energy expenditure and body composition. Descriptive statistics described the sample and MANOVA and ANOVA methods were used to evaluate differences between groups. RESULTS: Energy expenditure was significantly less for children with spina bifida who primarily used a wheelchair (p = .001) and children with Down syndrome (p = .041) when compared to children without a disability when adjusted for fat-free mass. However, no significant difference was detected in children with spina bifida who ambulated without assistance (p = .072). CONCLUSIONS: Children with spina bifida and Down syndrome have a significantly decreased energy expenditure which directly impacts recommended caloric intake. No significant difference was detected for children with spina bifida who ambulated, although the small sample size of this pilot study may have limited these findings. Validating these results in a larger study is integral to supporting successful weight management of these children.

Effect of adiposity on tissue-specific adiponectin secretion.

Circulating adiponectin levels are lower in individuals with increased BMI and central adiposity. However, they are paradoxically higher in those with peripheral adiposity. We hypothesized that adiponectin secretion from central and peripheral adipose tissue depots may be associated with adiposity levels and its distribution. A total of 55 subjects (69% women) undergoing elective abdominal surgery (mean age: 53 ± 13 years) were recruited. Health history, anthropometrics, and cardiovascular disease risk factor measurements were obtained. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples were obtained and cultured. Media was collected after 24hr and adiponectin released into the medium was measured using ELISA. We found that mean adiponectin levels from SAT and VAT in all subjects were 17.14±15.27 vs. 15.21±14.28 pg/ml/mg of tissue respectively (p = ns). However, adiponectin secretion from VAT correlated negatively with BMI (r = -0.31, p = 0.01), whereas there was no relationship with SAT (r = 0.08 p = 0.61). Similarly, waist circumference and estimated VAT percentage were both negatively correlated with VAT secretion of adiponectin (r = -0.35, p = 0.01 and r = -0.36, p = 0.02 respectively). These negative correlations were significant only in women on gender-stratified analyses. Adiponectin secretion from VAT decreases with increases in adiposity, while SAT secretion remains unchanged, especially in women. This observation may explain lower circulating adiponectin levels in individuals with central obesity. Further studies are needed to explore the mechanism behind this discrepant adiponectin secretion from SAT and VAT with increases in BMI, particularly among women.

Effect of gender and adiposity on in vivo vascular function in young African Americans.

The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = -0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = -0.34 and r = -0.48, respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings.