Nutrient deficiencies in children with celiac disease during long term follow-up.

BACKGROUND: Celiac disease (CD) is associated with malabsorption and consequential nutritional deficiencies. Patients with CD must follow a gluten-free diet (GFD), which is also associated with nutrient deficiencies. Despite the clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD and the usefulness of assessment during follow-up. The aim was to investigate the presence of micronutrient and protein deficiencies in pediatric patients with CD after starting a GFD and receiving standard clinical care, taking disease activity into account. METHODS: This single center retrospective chart review aimed to map the occurrence of nutrient deficiencies, determined in serum samples derived during follow-up in an expertise center for pediatric CD. Serological micronutrient levels were determined during routine clinical visits up until 10 years in children with CD on a GFD. RESULTS: The data of 130 children with CD was included. When pooling the measurements between 3 months and 10 years after GFD initiation, a deficiency in iron, ferritin, vitamin D, vitamin B12, folate and zinc was present in 33%, 21,9%, 21,1%, 2,4%, 4,3% and 8,1% of measurements, respectively. No hypocalcemia or vitamin B6 deficiency was found. CONCLUSION: The prevalence of deficiency varies amongst nutrients in children following a GFD, a high prevalence of some nutrient deficiencies is noteworthy. This study highlights the necessity to structurally investigate the risk of developing nutrient deficiencies while following a GFD. Knowledge of the risk to develop deficiencies can contribute to achieving a more evidence based approach in the management and follow-up of CD in children.

Socio-ecological determinants of lifestyle behavior of women with overweight or obesity before, during and after pregnancy: qualitative interview analysis in the Netherlands.

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.

Plant-based sterols and stanols in health & disease: "Consequences of human development in a plant-based environment?"

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.

Bariatric surgery in adolescents: a prospective randomized controlled trial comparing laparoscopic gastric banding to combined lifestyle interventions in adolescents with severe obesity (BASIC trial).

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.

Cirrhosis associated with decreased survival and a 10-year lower median age at death of cystic fibrosis patients in the Netherlands.

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 and1-1-2015. 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 < .01) and the median age at death (27 vs. 37 years; P = .02) was significantly lower in CFC compared to controls. In the deceased CFC patients, the reported primary cause of death was pulmonary in 68% of cases, and liver failure related in 18% of cases. 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.

Long-term effects of increased protein intake after weight loss on intrahepatic lipid content and implications for insulin sensitivity: a PREVIEW study.

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.

Effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity.

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.

Progress towards non-invasive diagnosis and follow-up of celiac disease in children; a prospective multicentre study to the usefulness of plasma I-FABP.

This prospective study investigates whether measurement of plasma intestinal-fatty acid binding protein (I-FABP), a sensitive marker for small intestinal epithelial damage, improves non-invasive diagnosing of celiac disease (CD), and whether I-FABP levels are useful to evaluate mucosal healing in patients on a gluten-free diet (GFD). Ninety children with elevated tTG-IgA titres and HLA-DQ2/DQ8 positivity were included (study group). Duodenal biopsies were taken, except in those fulfilling the ESPGHAN criteria. Plasma I-FABP levels and tTG-IgA titres were assessed sequentially during six months of follow-up. Eighty children with normal tTG-IgA titres served as control group. In 61/90 (67.8%) of the children in the study group an increased I-FABP level was found; in all these children CD diagnosis was confirmed. Interestingly, in 14/30 (46.7%) children with slightly elevated tTG-IgA titres (<10x upper limit of normal), an increased I-FABP level was found. In all these children the diagnosis of CD was confirmed histologically. After gluten elimination for six weeks I-FABP levels had decreased towards levels in the control group. Measurement of plasma I-FABP, in addition to tTG-IgA, EMA-IgA and HLAtyping, enables non-invasive diagnosing of CD in a substantial number of children, and might therefore be of value in the diagnostic approach of CD.

Sleep efficiency as a determinant of insulin sensitivity in overweight and obese adolescents.

UNLABELLED: 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.

Children With Morbid Obesity Benefit Equally as Children With Overweight and Obesity From an Ongoing Care Program.

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.

HLA frequencies and associations in cystic fibrosis.

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.

Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies.

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 < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). Upon a GFD serum levels decreased significantly, however, not within the range observed in controls, despite the common observed normalisation of IgA-tTG levels and Marsh grade. CD patients with elevated I-FABP levels nonresponding to GFD showed persistent histological abnormalities. CONCLUSIONS: Enterocyte damage assessed by serum I-FABP correlates with the severity of villous atrophy in coeliac disease at the time of diagnosis. Although enterocyte damage improves upon treatment, substantial enterocyte damage persists despite absence of villous atrophy and low IgA-tTG levels in the majority of cases. Elevated I-FABP levels nonresponding to gluten-free diet are indicative of histological abnormalities and warrant further evaluation.