Search

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterized by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease.METHODS: We performed untargeted liquid chromatography mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9,500 adults with metabolic phenotyping.RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (PC) and triglycerides (TG). Similar trends in PC and TG chain length and saturation were seen in adults with hepatic steatosis. However, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants.CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.

Background Recent studies have indicated that bariatric surgery is effective for the treatment of youth with severe obesity. The attitudes of pediatricians, parents, and adolescents regarding this topic remain unclear. Therefore, the aim of this study was to assess the current thoughts and beliefs of Dutch pediatricians, parents, and adolescents regarding bariatric surgery in youth. Methods An online survey containing twenty questions on bariatric surgery in youth was distributed to pediatricians of the Dutch Society of Pediatrics. Parents and adolescents who participated in an interdisciplinary care program for overweight, obesity, and severe obesity filled out an online survey of twelve questions. Results One hundred and twenty-one pediatricians, 49 parents, and 19 adolescents completed the surveys. Seventy-two pediatricians (59.5%) considered bariatric surgery to be an effective treatment for youth with severe obesity when conventional treatment fails, and intend to refer patients for bariatric surgery. The most frequently suggested conditions for bariatric surgery were a minimum age of 16 years (n = 59, 48.7%), a BMI threshold of 40 kg/m2 (n = 51, 42.2%), and a minimum Tanner stage of IV (n = 59, 48.8%). Thirty parents (61.2%) and fourteen adolescents (73.7%) responded that bariatric surgery should become available for youth with severe obesity. Conclusion Dutch pediatricians, parents, and adolescents increasingly accept bariatric surgery as a treatment modality in youth with severe obesity who do not respond successfully to lifestyle intervention. Whether pediatricians will actually refer youth for bariatric surgery remains to be seen when this treatment option will be implemented in the Netherlands. Graphical abstract

Objective: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). Study design: We conducted a clinical trial at 11 centers. Children aged 8 to 18 with IBD and anemia (defined as hemoglobin (Hb) z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary endpoint was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. Results: We randomized 64 patients (33 IV iron; 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P=0.01). At 3- and 6-months follow-up, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3 and 6 months after initiation of iron therapy (overall P=0.97). Conclusion: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral or IV therapy. The increase of Hb over time was comparable in both treatment groups. Trial registration: NTR4487 [Netherlands Trial Registry]. Keywords: Crohn’s disease; Ulcerative Colitis; anemia; children; iron suppletion.

Background Measures during the COVID-19 pandemic, including the closure of schools and sports facilities, may have lasting impact on the physical activity (PA) of children that persists for a long time. Objective To investigate the effect of COVID-19 measures on screen time and PA in Dutch children pre-, during- and post-school closures. Methods In cohort A (n = 102, 10.5 ± 3.6 years, 42.4% boys), data on PA and screen time during the lockdown were collected using a questionnaire. In cohort B (n = 131, 10.2 ± 0.9 years, 43.5% boys), data on PA and screen time were collected using a questionnaire and accelerometry 1 year before and after school closure. Results In cohort A, 62% reported less total PA. Self-reported screen time on week days increased 34 ± 105 min/d during the lockdown. In cohort B, sedentary time as measured by accelerometry, increased by 45 ± 67 min/d and only 20% reached PA levels of 60 min/d compared to 64% in May 2019. Self-reported screen time increased by 59 ± 112 min/d and 62 ± 130 min/d during week and weekend days, respectively. Conclusions Children were less physically active, and screen time was higher during and after the school closures due to the COVID-19 lockdown. This is alarming as an active lifestyle in children is crucial in preventing chronic diseases such as obesity.

Background: The COVID-19 pandemic has exacerbated the already existing pandemic of physical inactivity. In adolescents, the effect of COVID-19related governmental measures may beeven more pronounced,as they experience school closures, home confinement, social distancing and possible mental health issues as a result.The currentstudy uses the COVID-19 pandemic and associated governmental measures as a natural experiment to understand the impact it may have on the lifestyle of adolescents with relation to physical activity, sedentary and dietary behaviour. We also aim to describe the determinants of change in lifestyle behaviours.Methods/Design: A before-after experimental study design will be followed in which baseline measurements have been undertaken in 2018-19 before the COVID-19 pandemic, and the follow-up measurements will be repeated during the COVID-19 pandemic. Twenty government and private schools of Punjab, India form the primary unit of participation from which 1086adolescents participated in the study. Validated questionnaires are used to measurephysical activity, sedentarybehaviour, and dietary behaviour. Additionally, objective measures of physical activity will be performed using ActiGraph wGT3X-BT over a 7-day period on a sub-sample. Body mass index (BMI) and waist circumference will be assessed objectively as a measure of central obesity. Qualitative interviews and focus group discussions will be conducted to have a better understanding for reasons of change in physical activity, sedentary and dietary behaviour or any possible differences between groups.Discussion: The study aims torevealthe impact of COVID-19 governmental measures on physical activity, sedentary and dietary behaviour of adolescents. It is one of the first studies to show both subjective and objective measures of physical activity levels and sedentary time of school-going adolescents during COVID-19. Due to the mixed method approach we will be able to identify reasons for changes in lifestyle behaviours and possibly also detect innovative ways of stayingphysically active during the era of physical distancing.

Background Limited physical activity (PA) and a high level of sedentary time (ST) are associated with childhood obesity and are a target for intervention. This study aimed to assess objectively measured PA and ST in Dutch children across weight categories, age groups and sex. Methods 202 children with overweight, obesity and morbid obesity (55% girls, 12 ± 3y of age, BMI z-score + 3.15 ± 0.73), referred to the Centre for Overweight Adolescents and Children’s Healthcare (COACH, Maastricht UMC+) were included. PA (total PA, light PA and moderate to vigorous PA (MVPA)) and ST were measured with the GT3X Actigraph accelerometer. Wear time validation was set to include at least four days, 480 min/day, including one weekend day. Results PA levels in children with morbid obesity were higher compared to children with obesity, also after correction for age and sex (corrected difference (B) 118 counts per minute (cpm), p = .006). ST was lower in children with morbid obesity compared to children with obesity (B − 51 min/day, p = .018). Girls performed significantly less MVPA than boys (B − 11 min/day, p Conclusion PA and ST is different in subgroups of children with overweight, obesity and morbid obesity, depending on sex, age and overweight severity. In particular, children with obesity perform less PA and more ST compared to children with morbid obesity. Future research could explore the preferences and needs for PA and ST in children in the different weight categories. Trial registration The trial is registered with Clinicaltrials.govNCT02091544 at March 19, 2014.

Introduction: Lower urinary tract symptoms (LUTS) and gastrointestinal (GI) problems are common in Duchenne muscular dystrophy (DMD), but not systematically assessed in regular care. We aimed to determine the prevalence of bladder and bowel dysfunction (BBD) in DMD patients compared with healthy controls (HC). Methods: The Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ) based on the International Rome III criteria and the International Children’s Continence Society was filled out by 57 DMD patients and 56 HC. Additionally, possible associations of BBD with, for example, medication use or quality of life were evaluated in an additional questionnaire developed by experts. Results: In 74% of patients versus 56% of HC ≥ 1 LUTS (n.s.) were reported, 68% of patients versus 39% of HC reported ≥1 bowel symptom (p = 0.002) and 53% of patients versus 30% of HC reported combined LUTS and bowel symptoms (p = 0.019). A negative impact of BBD on daily life functioning was reported by 42% of patients. Conclusions: These data underscore that standard screening for BBD is needed and that the CBBDQ could be of added value to optimize DMD care.

INTRODUCTION: The effect of changes in body weight or insulin resistance on grey matter volume and cortical thickness change are unclear. The present observational study assessed effects of an 8-week weight loss period (≥8% of body weight), and a subsequent 22-month weight maintenance period on grey matter volume and cortical thickness.METHODS: A total of 24 participants (12f/12 m; age 52.8 ± 10.6 years) with overweight/obesity and pre-diabetes were recruited. T1-weighted magnetic resonance imaging was used to determine grey matter volume and cortical thickness at baseline, after the weight loss period and after a medium to high dietary protein weight maintenance period.RESULTS: At baseline, global grey matter volume was inversely associated with HOMA-IR, adjusted for sex and age (r = -0.42; p = .049). During the weight loss period participants decreased their BMI (32.1 ± 3.3 to 28.1 ± 2.8 kg/m2, p CONCLUSION: In conclusion, we confirmed that global grey brain matter volume was inversely associated with insulin resistance at baseline, yet an intervention yielding a decrease in insulin resistance did not lead to changes in global grey brain matter volume or cortical thickness.TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT01777893.

ContextChildhood obesity increases the risk of diseases as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease.ObjectiveTo evaluate the prevalence of comorbidities in school-age children with obesity and to compare its prevalence and the effect of a lifestyle intervention between children in primary and secondary school and between boys and girls.DesignCross-sectional analysis and lifestyle intervention.SettingCentre for Overweight Adolescent and Children’s Healthcare.PatientsComorbidities were evaluated in 149 primary and 150 secondary school children with (morbid) obesity (162 girls). The effect of lifestyle intervention was studied in 82 primary and 75 secondary school children.InterventionOne-year interdisciplinary lifestyle intervention.ResultsInsulin resistance (37%), impaired glucose tolerance (IGT) (3%), dyslipidemia (48%), hypertension (7%), and elevated liver transaminase levels (54%) were already common in primary school children. Glomerular hyperfiltration and insulin resistance were more prevalent in secondary school children. IGT was more prevalent in girls. The change in body mass index z score after intervention was greater in primary school children (primary vs secondary: −0.25 ± 0.32 vs −0.11 ± 0.47), even as the change in low-density lipoprotein cholesterol concentrations [primary vs secondary: −0.30 (interquartile range, −0.70 to 0.10) vs −0.10 (interquartile range, −0.40 to 0.30)] and systolic blood pressure z score (primary vs secondary: −0.32 ± 1.27 vs 0.24 ± 1.3). The change in body mass index z score, but not in comorbidities, was greater in boys (boys vs girls: −0.33 ± 0.45 vs −0.05 ± 0.31).ConclusionsThe presence of comorbidities is already evident in primary school children with obesity. The effect of a lifestyle intervention on these comorbidities is greater in primary compared with secondary school children, stressing the need for early interventions.

Background: Obesity and type 2 diabetes have been linked to alterations in food reward processing, which may be linked to insulin resistance.Objectives: In this clinical study, we investigated the respective contribution of insulin resistance, anthropometric measurements, and behavioral factors to brain reward activation in response to visual stimuli.Design: Food reward-related brain reward activation was assessed with functional magnetic resonance imaging in 39 overweight or obese individuals with impaired fasting glucose, impaired glucose tolerance, or both [22 women, 17 men; mean +/- SD insulin sensitivity index (ISI): 2.7 +/- 1.3; body mass index (BMI; kg/m(2)): 32.3 +/- 3.7; body fat percentage: 40.5% +/- 7.9%; fasting glucose: 6.3 +/- 0.6 mmol/L]. Food and nonfood images were shown in a randomized block design. Brain activation (food compared with nonfood images) was correlated with anthropometric and behavioral variables. Behavioral variables included eating behavior [Three-Factor Eating Questionnaire (TFEQ)] and habitual physical activity (Baecke). Glucose and insulin concentrations, determined during an oral-glucose challenge, were used to assess the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda ISI.Results: Food compared with nonfood brain activation was positively associated with HOMA-IR in the nucleus accumbens, right and left insula, and right cingulate gyrus (P Conclusions: Individuals with increased insulin resistance and emotional eating or disinhibition showed higher brain reactivity to food cues, which may imply changes in food preference and hyperphagia. Individuals with higher habitual physical activity showed less food reward-related brain activation.

Background: Pubertal insulin resistance (IR) is associated with increased risk of type 2 diabetes mellitus development in adolescents with overweight/obesity.Objectives: The PREVIEW study was a randomized parallel trial assessing the change in IR, analyzed by Homeostatic Model Assessment of IR (HOMA-IR), at 2 years after randomization to a high protein vs a moderate protein diet in adolescents with overweight/obesity. It was hypothesized that a high protein/low glycaemic index diet would be superior in reducing IR compared to a medium protein/medium GI diet, in insulin resistant adolescents with overweight or obesity.Methods: Adolescents with overweight/obesity and IR from the Netherlands, United Kingdom and Spain were randomized into a moderate protein/moderate GI (15/55/30En% protein/carbohydrate/fat, GI ≥ 56) or high protein/low GI (25/45/30En% protein/carbohydrate/fat, GI Results: 126 adolescents were included in this study (13.6 ± 2.2 years, BMI z-score 3.04 ± 0.66, HOMA-IR 3.48 ± 2.28, HP n = 68, MP n = 58). At 2 years, changes in protein intake were not significantly different between timepoints or intervention groups and no effects of the intervention on IR were observed. The retention rate was 39%, while no compliance to the diets was observed.Conclusions: The PREVIEW study observed no effect of a high protein/low GI diet on IR in adolescents with overweight/obesity and IR because of lack of feasibility, due to insufficient retention and dietary compliance after 2 years.

Background: Reduced physical activity (PA) is associated with childhood obesity and is a target for intervention. This study aimed to assess objectively measured PA patterns in Dutch children across weight categories, age groups and gender at the start of a lifestyle intervention.Methods: 202 children with overweight and (morbid) obesity (55% girls, 12±3y of age, BMI z-score +3.15±0.73), referred to the Centre for Overweight Adolescents and Children’s Healthcare (COACH, Maastricht UMC+) were included. Children were categorized as overweight, obese or morbidly obese according to their BMI z-score. PA patterns (total PA, sedentary time (ST), light PA and moderate to vigorous intensity PA (MVPA)) werewas measured with the GT3X Actigraph accelerometer. Wear time validation was set on four days, 480 min/day, including one weekend day.Results: PA levels in children with morbid obesity were higher compared to children with obesity, also after correction for age and gender (corrected difference (B) 118 counts per minute (cpm), p=.006). Sedentary behaviour (STB) was lower in children with morbid obesity compared to children with obesity (B -51 min/day, p=.018). Girls performed significantly less moderate to vigorous MVPA than boys (B -11 min/day, pConclusion: Weight category morbid obesity, younger age and male gender were positively associated with PA and negatively with SB. PA and ST is different in subgroups of children with overweight and (morbid) obesity, depending on gender, age and overweight severity. In particular in older girls in the weight category ‘obesity’, levels of PA and ST are worrisome. These findings highlight the need for tailored PA promotion. Trial registration: The trial is registered with Clinicaltrials.gov NCT02091544

BACKGROUND Despite the well-known beneficial health effects of physical activity (PA), the majority of Dutch primary school children do not meet the recommended PA guidelines. Although there is growing evidence on the effectiveness of exergames for PA in children, there is limited evidence on their effect on health outcomes, such as cardiovascular health and health-related quality of life (HRQOL), and on factors influencing their effectiveness and feasibility. The exergame BOOSTH uses a wrist-worn activity tracker to measure steps per day. As a reward for the performed PA, children can unlock levels in the online BOOSTH game. In addition, “BOOSTH battle” enables competition between groups. OBJECTIVE This protocol describes a cluster randomized controlled trial in 16 primary schools in the Netherlands investigating the effect of BOOSTH on moderate-to-vigorous PA (MVPA) using accelerometry. Secondary aims are to investigate the feasibility of BOOSTH (mixed methods: questionnaires and focus group interviews) and its effect on cardiovascular risk factors (anthropometrics, blood pressure, and retinal microvasculature) and HRQOL. METHODS Stratification variables and relevant variables related to outcomes (such as BMI [z-score], sex, age, and parenting style) and/or missingness will be taken into account. Measurements will be performed at baseline and after 3, 6, and 12 months. RESULTS The study has received funding from Province Limburg (SAS-2015-04956) and received ethical approval from the Medical Ethics Committee of Maastricht University Medical Centre (METC172043/NL64324.068.17). The results of the analyses are expected to be published in 2021. CONCLUSIONS With this study, the ability of the exergame BOOSTH to increase PA and improve health in children of primary school age will be investigated. The insights into effectiveness and feasibility will result in scientific and societal recommendations, which could potentially contribute to widespread implementation of exergames for children. CLINICALTRIAL ClinicalTrials.gov NCT03440580; https://clinicaltrials.gov/ct2/show/NCT03440580. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/24035

Background & aimsGenome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics.Methods960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1.Resultsrs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (PA in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1.ConclusionsThere are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD.

Background Recent data support the use of bariatric surgery in adolescents with severe obesity following unsuccessful non-surgical treatments. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have demonstrated reasonably similar weight loss and reduction of obesity related comorbidities in randomized trials in adults. SG has internationally become the most commonly used procedure in adolescents, yet long-term outcome data are lacking. No randomized controlled trial comparing SG and RYGB has been performed in adolescents. Objective Determine whether SG is non-inferior to RYGB in terms of total body weight (TBW) loss in adolescents with severe obesity. Methods A multicenter randomized controlled non-inferiority trial. Two hundred sixty-four adolescents aged 13–17 (Tanner stage ≥IV) with severe obesity (corrected for age and sex) will be included. Adolescents agreeing to participate will be randomized to either RYGB or SG. The primary outcome is the proportion of participants achieving 20% TBW loss at 3 years postoperatively. Secondary outcomes include (i) change in body weight, body mass index (BMI) and BMI standard deviation score, (ii) incidence of adverse health events and need for additional surgical intervention, (iii) resolution of obesity-related comorbidities, (iv) prevalence of cardio metabolic risk factor measures, (v) bone health measures and incidence of bone fractures, (vi) quality of life including psychosocial health, patient satisfaction and educational attainment and (vii) body composition. Follow-up will extend into the long term. Results Not applicable. Discussion This study will, to our knowledge, be the first randomized controlled trial comparing SG and RYGB in adolescents with severe obesity. Trial registration The trial is registered at the Netherlands Trial Register on July 26th, 2018 – NTR7191 - https://www.trialregister.nl/trial/7191 (protocol version 5.0 – February 3th 2020).

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children and adults characterized by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. We hypothesized that change in the concentration of lipid species in pediatric NAFLD would mimic the alterations known to be associated with CVD in adults (and be largely reflective of insulin resistance). Here, we performed untargeted liquid chromatography mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9,500 adults with metabolic phenotyping. Phosphatidylcholine (PC) and triglyceride (TG) desaturation and chain length were inversely associated with histological severity of paediatric NAFLD. Nine lipids species (lyso-PC, PC, and TG classes) were also associated with hepatic steatosis and insulin resistance in an independent cohort of adults. Five of the 9 lipids replicated in the adults cohort (including PC(36:4)) have been directly linked to death and cardiometabolic disease in adults, as well as indirectly via genetic variants that influence the concentration of these species. Together, these findings suggest that lipid metabolism is altered in paediatric NAFLD in a similar way as in cardiometabolic disease in adults and it is therefore critical to alleviate insulin resistance in these children to mitigate their long-term morbidity.

Previous studies demonstrated that hyperglycemic glucose concentrations are observed in children that are overweight or have obesity. The aim of this study was to evaluate the effect of a 12 month lifestyle intervention on free-living glycemic profiles in children that were overweight or had obesity, and the association of the alterations with changes in cardiovascular risk parameters. BMI z-score, free-living glycemic profiles, continuous overlapping net glycemic action (CONGA), and cardiovascular parameters were evaluated before and after a multidisciplinary lifestyle intervention, in 33 non-diabetic children that were overweight or had obesity. In children with a decrease in BMI z-score, the duration which glucose concentrations were above the high-normal threshold (6.7 mmol/L) and the glycemic variability decreased significantly. In these children, a decrease in median sensor glucose was associated with decreases in LDL-cholesterol, and systolic and diastolic blood pressure z-score. A decrease in BMI z-score was associated with a decrease in CONGA1, 2, and 4. In conclusion, the glycemic profiles in free-living conditions in children that were overweight improved in children with a decrease in BMI z-score after lifestyle intervention. In those children, changes in median sensor glucose concentrations were associated with changes in LDL-cholesterol and blood pressure z-scores. These results suggest that glucose homeostasis can improve after one year of lifestyle intervention and that these improvements are associated with improvements in cardiovascular health parameters.

Background Maternal overweight and obesity are related to several health risks in the periods before, during and after pregnancy including a higher risk of gestational diabetes mellitus, preeclampsia and preterm birth. At the same time, women’s daily life quickly changes in these periods. Therefore, we hypothesize that the value of determinants of lifestyle behavior within different levels of the socio-ecological model differ accordingly and influence lifestyle behavior. These dynamics of determinants of lifestyle behavior in the periods before, during and after pregnancy are unexplored and therefore evaluated in this study. These insights are needed to offer appropriate guidance to improve lifestyle in women of childbearing age. Methods Individual semi-structured interviews were conducted before, during or after pregnancy in 26 women with overweight or obesity living in the Netherlands. Questions covered all levels of the socio-ecological model, i.e. intrapersonal, interpersonal, institutional and environmental/societal. All interviews were transcribed and coded. Results Determinants at all levels of the socio-ecological model were perceived as relevant by women of childbearing age. Various determinants were mentioned including knowledge of a healthy lifestyle, social support, access to customized lifestyle guidance, and distance to healthy lifestyle supporting activities. The importance women attributed to determinants differed between the periods before, during and after pregnancy. Before pregnancy, child’s wellbeing as motivator for adopting a healthy lifestyle was mentioned less frequently than during and after pregnancy. Women described that the interplay and balance between determinants varied on a daily basis, and not merely per period. This was often expressed as fluctuation in energy level per day which influences their willingness to put effort in making healthy choices. Conclusions Findings of this study confirm the importance of determinants at multiple socio-ecological levels for shaping lifestyle behavior in women of childbearing age. The findings add to current insights that the perceived importance of determinants and their interplay differ before, during and after pregnancy. They influence lifestyle behavior decisions, not only per period but even on a daily basis, in particular in this phase of life. This perspective can be helpful in optimizing lifestyle guidance for women of childbearing age in order to prevent perinatal complications.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30 years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.

Objective Morbid obesity is the fastest growing subcategory of childhood obesity, associated with an increased health risk that persists into adulthood. There is an urgent need to develop multifaceted interventions that target initial and long-term lifestyle changes. This review investigates the effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity. The influence of age, gender and family participation on health outcomes and intensive treatment alternatives are explored. Methods The review includes 16 studies conducted between 1995 and 2017. Studies examined youth with morbid obesity, 4-18 years old, undergoing multidisciplinary treatment. Results All studies found a reduction in body mass index (BMI or z-score) and if measured, cardiovascular risk factors. Physical activity, nutrition education, behavioural modification and family involvement are commonly included treatment components and have improved weight loss and health-related outcomes. However, initial weight loss was often not sustainable, despite the favourable interventional effect on cardiometabolic risk markers. Weight loss was prolonged in younger children and among the male sex. Conclusions There is not a 'one-size-fits-all' treatment approach, and matched care to personal needs is preferable. The integration of a chronic care approach is critical for the successful adaption of sustainable health behaviours.

Background In children and teenagers with Inflammatory Bowel Disease (IBD) and iron deficiency anaemia, administration of iron is recommended to replete empty iron stores, but the most effective route of administration remains unknown. We compared intravenous (IV) and oral iron therapy and evaluated physical fitness and haemoglobin (Hb) improvement over time. Methods We performed an international multicentre randomized controlled trial (NTR: 4487) in patients aged 8-18 years with IBD and anaemia (defined as Hb > 2 standard deviations (SD) below the reference mean according to WHO cut-offs). Children with severely active disease (PUCAI ≥ 65 or PCDAI ≥ 30) at baseline were excluded. Patients were randomly assigned to receive either IV iron via a single infusion of ferric carboxymaltose (15 mg/kg, maximum 750 mg) or oral iron using ferrous fumarate 9 mg/kg/day in 2 doses (maximum 600 mg) for 12 weeks. The primary outcome was improvement of physical fitness, defined as an increase in 6-minute walking distance (6MWD) over time and expressed as z-score to allow correction for age and gender. Secondary outcome was an increase in Hb z-score. Linear mixed models were used to analyse effect of treatment on 6MWD and Hb z-score at each follow-up visit controlling for disease activity, IBD diagnosis, study centre and outcome at baseline. Results We randomised 64 patients (33 IV iron; 31 oral iron). One month after the start of iron therapy, increase of 6MWD z-scores was significantly larger in the IV group compared to the oral group (0.75 SD vs. -0.16 SD, P=0.006, Figure 1). At 3- and 6-months follow-up, no significant differences in 6MWD z-scores were observed between groups. Hb z-scores gradually increased over time in both groups, but there was no significant difference in change from baseline between groups at 1, 3 and 6 months after initiation of iron therapy (overall P=0.97, Figure 2). Figure 1: Mean 6-minute walking distance (6MWD) z-scores in relation to start of iron treatment Figure 2: Mean haemoglobin (Hb) z-scores in relation to start of iron treatment Conclusion In this head-to-head randomized controlled trial involving paediatric patients with IBD and anaemia, IV iron was superior to oral iron with respect to early improvement of physical fitness. However, this effect subsided over time and improvement of Hb was similar for both types of iron therapy.

Context: Overweight and obese children have an increased risk to develop cardiovascular diseases (CVDs) in which thyroid-stimulating hormone (TSH) has been suggested as an intermediary factor. However, results of cross-sectional studies are inconclusive, and intervention studies investigating changes in TSH concentrations in association with changes in cardiovascular risk parameters in overweight and obese children are scarce.Objective: To gain insight in associations of circulating TSH concentrations and cardiovascular risk parameters in overweight and obese children.Design: Nonrandomized lifestyle intervention.Setting: Centre for Overweight Adolescent and Children's Healthcare.Patients: Three hundred thirty euthyroid overweight and obese children.Intervention: Long-term lifestyle intervention.Main Outcome Measures: TSH concentrations, pituitary TSH release in response to thyrotropin-releasing hormone (TRH), and cardiovascular risk parameters.Results: At baseline, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), and monocyte chemotactic protein 1 concentrations were significantly associated with serum TSH concentrations. TSH release by the pituitary in response to exogenous TRH was not associated with cardiovascular risk parameters. During lifestyle intervention, several cardiovascular risk parameters significantly improved. In children whose body mass index z score improved, changes in TSH concentrations were significantly associated with changes in TC, LDL-C, and TAG concentrations.Conclusions: In euthyroid overweight and obese children, circulating TSH concentrations are positively associated with markers representing increased CVD risk. Changes in TSH concentrations are also associated with changes in lipid concentrations in children with successful weight loss, which is consistent with TSH being an intermediary factor in modulating lipid and lipoprotein metabolism.

Contains fulltext : 229336.pdf (Publisher’s version ) (Open Access) Prepregnancy overweight and obesity are associated with higher risk of perinatal complications. However, the effect of weight change prior to pregnancy on perinatal outcome is largely unknown. Therefore, it is aimed to examine the impact on perinatal outcomes of interpregnancy BMI change in women of different BMI categories. The MEDLINE, EMBASE, LILACS, and CINAHL databases were searched (1990-August 2019). Observational studies on interpregnancy BMI change were selected. Outcomes evaluated were gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension (GH), cesarean section, preterm birth, and newborns being large (LGA) or small (SGA) for gestational age. Meta-analyses and meta-regression analyses were executed. Thirty studies were included (n > 1 million). Interpregnancy BMI gain was associated with a higher risk of GDM (for BMI gain ≥3 kg/m(2) : OR 2.21; [95%CI 1.53-3.19]), preeclampsia (1.77 [1.53-2.04]), GH (1.78 [1.61-1.97]), cesarean section (1.32 [1.24-1.39]), and LGA (1.54 [1.28-1.86]). The effects of BMI gain were most pronounced in women with BMI

Background: Although children seem to be at a lower risk for severe COVID-19 infection, governmental regulations to prevent the spread of the virus possibly affect their lifestyle and related health. In the Netherlands, controlled lock-down measures included closure of schools, daycare and sports facilities. In this study screen time and self-reported and objectively measured physical activity (PA) was investigated among Dutch children before and during the COVID-19 pandemic. Methods: Data derived from two different cohorts were used. In cohort A (102 children, 10.5 ± 3.6 year, 42.4% boys) PA and screen time were evaluated with questionnaires regarding the pre-pandemic situation and regarding the situation during the COVID-19 pandemic. 131 children (10.2 ± 0.9 year, 43.5% boys) from cohort B filled out questionnaires on PA and screen time and wore an ActiGraph accelerometer, after reopening of schools and one year earlier. Findings: Seventy-five percent of children in cohort A reported less total PA during the controlled lock-down. Total screen time on weekdays significantly increased by 34± 105 min/day. Compared to May 2019, children in cohort B reported to spend less time on sports during the pandemic. Objectively measured sedentary time increased with 45 ± 67 min/day compared to May 2019. Children that spent a minimum of 60 min/day on moderate-to-vigorous intensity PA decreased from 64% to 20%. Screen time increased by 59 ± 112 min/day on week days and 62 ± 130 min/day on weekend days for children in cohort B. Interpretation: During the COVID-19 pandemic, PA levels decreased and screen time increased during and directly after the controlled lockdown. This is alarming as a healthy, active lifestyle in children is crucial in preventing chronic diseases. Trial Registration: Clinicaltrials.gov (NCT04411511 and NCT03440580), for cohort A and B respectively. Funding: Data from children from cohort B was collected from an ongoing study which received funding from Province Limburg (SAS-2015-04956). Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: Both studies were reviewed and approved by the Medical Ethics Committee of the Maastricht University Medical Centre+ (METC2020-1330-A-1 and METC172043/NL64324.068.17).

Obesity causes modifications in the kidneys reversed by weight loss in adults. There is little data on renal function and effects of weight loss in children with obesity. The aim of this prospective study was to examine renal function and effect of a lifestyle intervention in children with overweight, obesity and morbid obesity. Two hundred forty-five children (age 12.4 ± 3.3 years, 40% boys, BMI z-score 3.46 ± 0.70) participating in an out-patient lifestyle intervention were included. Children with at least 12 months follow-up (n = 144 (58.8%)) were included in the longitudinal study. Anthropometry, blood analysis and blood pressure measurements were performed at baseline and follow-up. Glomerular filtration rate (GFR) was estimated using the Schwartz and FAS equation. eGFR was de-indexed using body surface area. Different cut-off points for defining glomerular hyperfiltration were used for stratification. Depending on the definition and equation used, glomerular hyperfiltration was present in 2% to 18% of the participants. After intervention, de-indexed eGFR decreased significantly in children with baseline glomerular hyperfiltration, depending on the eGFR equation and definition for glomerular hyperfiltration used. No associations of changes in eGFR with changes in BMI z-score, blood pressure or parameters of glucose and lipid metabolism were found. In conclusion, after one year of lifestyle intervention, eGFR decreases in hyperfiltrating children and adolescents with overweight, obesity and morbid obesity. eGFR and changes over time in children with obesity depend on eGFR equation used and on de-indexing for body surface area.

Background and aim Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD-associated HLA polymorphisms using buccal swabs as routine test in high-risk individuals. Methods Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self-administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA-DRB1, HLA-DQA1, and HLA-DQB1 typing was examined on buccal cell-derived and blood-derived DNA at low and, if necessary, high resolution level, using sequence-specific oligonucleotide and sequence-based typing, respectively. Results DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA-DQ typing in all individuals. HLA typing results on buccal cell-derived DNA were identical to typing on blood-derived DNA, also for the self-administered samples. Conclusion Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self-administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high-risk populations.

OBJECTIVES: Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD. METHODS: Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh: Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects. RESULTS: Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r = 0.458, P = 0.042) and at day 14 (r = 0.654, P = 0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC. CONCLUSIONS: Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.

Objective: To investigate associations between weight status and physical activity, psychosocial impulsive, and reflective determinants of exercise behavior in youngsters (8–18 years old), distinguishing between strength exercises and aerobic exercises. Method: Cross-sectional survey of 133 youngsters (89 girls – 59 youngsters who are being treated for obesity in an outpatient lifestyle intervention program, plus 74 youngsters from the general population). In order to identify reflective determinants, participants completed questionnaires. For the impulsive determinants, participants completed two computerized reaction time sorting-tasks (‘Implicit Association Tests’). Results: Exercise intentions, including those for aerobic and strength exercises, were positively correlated with BMI z-scores. Youngsters with a higher BMI z-score often reported that their friends think they should exercise and were more confident that they could exercise more if they wanted to. No other determinants, including impulsive determinants, were correlated with BMI z-scores. Conclusion: In terms of reflective determinants, few differences were found between youngsters with higher BMI z-scores as compared to youngsters with lower BMI z-scores. There was no significant correlation between BMI z-score and the impulsive determinants of aerobic versus strength exercise. This suggests that youngsters, independent from weight status feel that they could be reached by the same kind of physical activity intervention.

Background Obesity in children and adolescents is an increasing problem associated with multiple co-morbidities including metabolic and endocrine changes, cardiovascular abnormalities, and impaired quality of life. Combined lifestyle interventions are the current standard treatment for severe obesity in children. However, the medium- and long-term results of these interventions are relatively poor. Bariatric surgery shows substantial weight loss and health improvement in adults and retrospective studies in adolescents show similar outcomes. However, well-designed prospective studies in this young age group are rare. Our objectives are to determine whether combining surgery with lifestyle interventions in severely obese adolescents leads to a significant additional weight reduction compared to lifestyle interventions solely, and to assess its effect on obesity-associated co-morbidities in a prospective randomized controlled setting. Methods Patients aged 14–16 years with sex- and age-adjusted BMI > 40 kg/m2 (or > 35 kg/m2 with comorbidity) and failure to achieve weight reduction > 5% during at least one year of combined lifestyle interventions are included in this trial. Randomization determines whether laparoscopic adjustable gastric banding will be added to combined lifestyle intervention throughout the trial period. Sixty children will be included in this trial. Follow-up visits are planned at 6 months, 1,2 and 3 years. Primary endpoints are percentage of total weight loss, and change of BMI. Secondary endpoints include body composition, pubertal development, metabolic and endocrine changes, inflammatory status, cardiovascular abnormalities, non-alcoholic steatohepatitis, quality of life and changes in behaviour. Discussion This randomized controlled trial is designed to provide important information about the safety and efficacy of laparoscopic adjustable gastric banding treatment in severely obese adolescents with unsuccessful combined lifestyle interventions. The reversibility of this surgical procedure forms a strong argument to decide for gastric banding over other surgical procedures, since bariatric surgery in adolescents is still in its infancy. Trial registration The BASIC trial is registered in the register of ClinicalTrials.gov since July 2010, Identifier: NCT01172899 Electronic supplementary material The online version of this article (10.1186/s12887-019-1395-9) contains supplementary material, which is available to authorized users.

Background: Up to 10% of patients with Cystic Fibrosis develop cirrhotic CF-related liver disease with portal hypertension: CF cirrhosis (CFC). In a nationwide study, we aimed to determine the role of CFC on survival in the Netherlands between 1 and 1-2009 and 1-1-2015.Methods: We identified all CFC patients in the Netherlands, based on ultrasonographic liver nodularity and portal hypertension. A non-cirrhotic control group was obtained from the national Dutch CF patient registry. We compared groups with regards to baseline lung function and nutritional status and survival and age at death over a 6-year period. In case of death of CFC patients, the clinical reported cause was recorded.Results: At baseline, we found no significant difference in lung function and nutritional status between the CFC patients (N = 95) and controls (N = 980). Both the 6-year survival rate (77 vs. 93%; P Conclusions: In the Netherlands, the presence of CFC is associated with a higher risk for early mortality and an approximately 10-year lower median age at death. This substantial poorer outcome of CFC patients was not reflected in a lower baseline lung function or a diminished nutritional status. However, in the case of mortality, the reported primary cause of death in CFC patients is predominantly pulmonary failure and not end-stage liver disease. (C) 2018 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

The aim of this study was to assess the effects of a weight maintenance period comprising two diets differing in protein intake, after weight loss, on intrahepatic lipid content and implications for insulin sensitivity. A total of 25 participants [body mass index (BMI): 31.1 (3.5 kg/m2; intrahepatic lipid (IHL): 8.7 (8.3%; fasting glucose: 6.4 (0.6 mmol/l; homeostatic model assessment for insulin resistance (HOMA-IR): 3.7 (1.6; Matsuda index: 3.4 (2.9] started an 8-wk low-energy diet followed by a 2-yr weight maintenance period with either high protein or medium protein dietary guidelines. At baseline, after 6 mo, and after 2 yr, IHL, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were determined by magnetic resonance spectroscopy/imaging. Glucose and insulin concentrations, determined during an oral glucose challenge, were used to assess the HOMA-IR and Matsuda insulin sensitivity index (ISI). Protein intake was measured with 24-h urinary nitrogen excretion. Protein intake, BMI, IHL, VAT, SAT, HOMA-IR, and ISI did not change differently between the groups during the intervention. In the whole group, BMI, IHL, VAT, SAT, HOMA-IR, and ISI were favorably changed at 6 mo and 2 yr compared with baseline ( P < 0.05). Mixed-model analysis showed that independent of BMI, protein intake (g/d) at 6 mo was inversely related to IHL (coefficient: −0.04; P < 0.05) and VAT (coefficient: −0.01; P < 0.05). Overall, IHL was positively related to HOMA-IR (coefficient: 0.10; P < 0.01) and inversely related to ISI (coefficient: −0.17; P < 0.01), independent of BMI. A 2-yr medium- to high-protein energy-restricted diet reduced IHL and VAT. Independently of changes in BMI, IHL was inversely related to insulin sensitivity.

The objective was to assess the effects of a weight loss and subsequent weight maintenance period comprising two diets differing in protein intake, on brain reward reactivity to visual food cues. Brain reward reactivity was assessed with functional magnetic resonance imaging in 27 overweight/obese individuals with impaired fasting glucose and/or impaired glucose tolerance (HOMA-IR: 3.7 &plusmn, 1.7, BMI: 31.8 &plusmn, 3.2 kg/m2, fasting glucose: 6.4 &plusmn, 0.6 mmol/L) before and after an 8-week low energy diet followed by a 2-year weight maintenance period, with either high protein (HP) or medium protein (MP) dietary guidelines. Brain reactivity and possible relationships with protein intake, anthropometrics, insulin resistance and eating behaviour were assessed. Brain reactivity, BMI, HOMA-IR and protein intake did not change differently between the groups during the intervention. In the whole group, protein intake during weight maintenance was negatively related to changes in high calorie images&gt, low calorie images (H &gt, L) brain activation in the superior/middle frontal gyrus and the inferior temporal gyrus (p &lt, 0.005, corrected for multiple comparisons). H &gt, L brain activation was positively associated with changes in body weight and body-fat percentage and inversely associated with changes in dietary restraint in multiple reward, gustatory and processing regions (p &lt, 0.005, corrected for multiple comparisons). In conclusion, changes in food reward-related brain activation were inversely associated with protein intake and dietary restraint during weight maintenance after weight loss and positively associated with changes in body weight and body-fat percentage.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD. Methods: Out of the 138 individuals (age: 46.3 ± 8.9, body mass index: 43.3 ± 6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD. Within the NAFLD group, 28 had simple steatosis and 27 had non-alcoholic steatohepatitis. Plant sterols and sitostanol were measured from serum (n=138), liver (n=38), and bile (n=41). The mRNA expression of genes regulating liver sterol metabolism and inflammation was measured (n=102). Results: Liver and bile sitostanol ratios to cholesterol were higher in those with NAFLD compared to those with histologically normal liver (all P 0.407, P

Purpose: This study aimed to evaluate the long-term effectiveness and cost-effectiveness of high intensity (HI) versus low-to-moderate intensity (LMI) exercise on physical fitness, fatigue, and health-related quality of life (HRQoL) in cancer survivors. Methods: Two hundred seventy-seven cancer survivors participated in the Resistance and Endurance exercise After ChemoTherapy (REACT) study and were randomized to 12 weeks of HI (n = 139) or LMI exercise (n = 138) that had similar exercise types, durations, and frequencies, but different intensities. Measurements were performed at baseline (4–6 weeks after primary treatment), and 12 (i.e., short term) and 64 (i.e., longer term) weeks later. Outcomes included cardiorespiratory fitness, muscle strength, self-reported fatigue, HRQoL, quality-adjusted life years (QALYs) and societal costs. Linear mixed models were conducted to study (a) differences in effects between HI and LMI exercise at longer term, (b) within-group changes from short term to longer term, and (c) the cost-effectiveness from a societal perspective. Results: At longer term, intervention effects on role (β = 5.9, 95% CI = 0.5; 11.3) and social functioning (β = 5.7, 95%CI = 1.7; 9.6) were larger for HI compared to those for LMI exercise. No significant between-group differences were found for physical fitness and fatigue. Intervention-induced improvements in cardiorespiratory fitness and HRQoL were maintained between weeks 12 and 64, but not for fatigue. From a societal perspective, the probability that HI was cost-effective compared to LMI exercise was 0.91 at 20,000€/QALY and 0.95 at 52,000€/QALY gained, mostly due to significant lower healthcare costs in HI exrcise. Conclusions: At longer term, we found larger intervention effects on role and social functioning for HI than for LMI exercise. Furthermore, HI exercise was cost-effective with regard to QALYs compared to LMI exercise. Trial registration: This study is registered at the Netherlands Trial Register [NTR2153 [http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2153]] on the 5th of January 2010. Implications for Cancer Survivors: Exercise is recommended to be part of standard cancer care, and HI may be preferred over LMI exercise.

CONTEXT: Despite stabilization of childhood overweight and obesity prevalence, there is a shift toward more severe degrees of obesity, which results in an increasing prevalence of children with morbid obesity. Prior studies demonstrated that lifestyle modification without ongoing treatment has only a modest and not sustainable effect in children with morbid obesity. This suggests that a chronic care model is necessary for long-term effects on weight management and health. OBJECTIVE: This study aimed to evaluate the effect of an ongoing lifestyle intervention in children with morbid obesity in comparison with children with overweight and obesity. DESIGN AND SETTING: This was a nonrandomized prospective intervention study with 12- and 24-month followup at the Centre for Overweight Adolescent and Children's Healthcare. PATIENTS AND INTERVENTION: Children and adolescents (n = 100 females and 72 males) with overweight, obesity, or morbid obesity were given long-term, outpatient, tailored lifestyle intervention. MAIN OUTCOME MEASURE: Body mass index (BMI) z score was measured. RESULTS: In children with morbid obesity, 12- and 24-month interventions resulted in a decrease of BMI z score of -0.13 +/- 0.25 (P = .001) and -0.23 +/- 0.32 (P = .01) respectively, whereas weight status category improved to obese in 21% and 25% of the children. Cardiovascular risk parameters including serum total cholesterol, low-density lipoprotein cholesterol, glycosylated hemoglobin (HbA1c), and diastolic blood pressure significantly improved after 1-year intervention in the complete group. Most important, BMI z score as well as cardiovascular risk parameters improved to a similar degree in children with overweight, obesity, and morbid obesity. CONCLUSIONS: Children with overweight, obesity, and morbid obesity benefit equally from an ongoing, outpatient, tailored lifestyle intervention, and demonstrate significant weight loss and improvement of cardiovascular risk parameters.

Insulin resistance (IR) occurs in a transient manner during puberty. Obese adolescents may be at risk for persistent IR during puberty. The objective of the study is to review the literature on the association of the anthropometry and lifestyle characteristics with insulin sensitivity in overweight and obese adolescents, and include data from a new study. Relevant papers were selected and reviewed. In addition, 137 overweight and obese adolescents (42 male/95 female, age 14.4 +/- 2.3 years, BMI z-score +3.3 +/- 0.7, HOMA-IR 3.4 +/- 1.8) from the Centre for Overweight Adolescent and Children's Healthcare (MUMC+) were included in this study. Anthropometrics, Tanner stages, sleep characteristics, food intake behaviour and physical activity were determined, and possible associations with homeostasis model assessment of insulin resistance (HOMA-IR) were tested. RESULTS: Overweight and obese adolescents with unfavourable fat partitioning and family history of NIDDM are at risk for persistent IR. Overweight and obese adolescents from the new cohort showed a higher HOMA-IR postpubertally. BMI z-score, age, pubertal stage and prepubertally total sleeping time (TST) and sleep efficiency (SE) were identified as significant contributors. Overweight and obese adolescents showed a persistently higher instead of transiently higher HOMA-IR during puberty, associated with BMI z-score, age, pubertal stage and prepubertally less TST and SE.

Insulin resistance (IR) in adolescence is associated with type 2 diabetes mellitus [T2DM]. The PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study assessed the effectiveness of a high-protein, low-glycaemic-index diet and a moderate-protein, moderate-glycaemic-index diet to decrease IR in insulin-resistant children who were overweight or obese. Inclusion criteria were age 10 to 17 years, homeostatic model assessment of IR (HOMA-IR) ≥2.0 and overweight/obesity. In 126 children (mean ± SD age 13.6 ± 2.2 years, body mass index [BMI] z-score 3.04 ± 0.66, HOMA-IR 3.48 ± 2.28) anthropometrics, fat mass percentage (FM%), metabolic characteristics, physical activity, food intake and sleep were measured. Baseline characteristics did not differ between the groups. IR was higher in pubertal children with morbid obesity than in prepubertal children with morbid obesity (5.41 ± 1.86 vs 3.23 ± 1.86; P = .007) and prepubertal and pubertal children with overweight/obesity (vs 3.61 ± 1.60, P = .004, and vs 3.40 ± 1.50, P < .001, respectively). IR was associated with sex, Tanner stage, BMI z-score and FM%. Fasting glucose concentrations were negatively associated with Baecke sport score (r = -0.223, P = .025) and positively with daytime sleepiness (r = 0.280, P = .016) independent of sex, Tanner stage, BMI z-score and FM%. In conclusion, IR was most severe in pubertal children with morbid obesity. The associations between fasting glucose concentration and Baecke sport score and sleepiness suggest these might be possible targets for diabetes prevention.

Cystic fibrosis (CF) is classically attributed to the dysfunction of the single CF transmembrane conductance regulator gene. The incidence of human leukocyte antigen (HLA) polymorphisms in different CF-associated diseases raises the question of an unequal distribution of HLA genotypes in CF. This study aimed to evaluate HLA gene frequencies and possible associations in CF patients compared with a control population. Frequencies of HLA-DRB1, HLA-DQA1 and HLA-DQB1, performed by intermediate resolution typing using Luminex sequence-specific oligonucleotide, and epitope counts were similar in 340 CF patients when compared with 400 control subjects. In conclusion, HLA-DRB1, -DQA1 and -DQB1 do not seem to influence susceptibility to CF. Whether HLA plays a role in the severity of CF disease needs to be investigated.

Background: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy–enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. Objective: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. Design: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. Results: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 μmol · kg−1 · h−1; S-formula: 130 ± 53 μmol · kg−1 · h−1; P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 μmol · kg−1 · h−1; S-formula: 0.84 ± 0.36 μmol · kg−1 · h−1; P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. Conclusion: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515.

Summary Background Enterocyte damage is the hallmark of coeliac disease (CD) resulting in malabsorption. Little is known about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a sensitive marker to study enterocyte damage. Aims To evaluate the severity of enterocyte damage in adult-onset CD and its course upon a gluten-free diet (GFD). Furthermore, the correlation among enterocyte damage, CD autoantibodies and histological abnormalities during the course of disease is studied. Methods Serum I-FABP levels were determined in 96 biopsy-proven adult CD patients and in 69 patients repeatedly upon a GFD. A total of 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels served as controls. I-FABP levels were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. Results I-FABP levels were elevated in untreated CD (median 691 pg/mL) compared with controls (median 178 pg/mL, P

Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.