The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study.

BACKGROUND: Children with obesity have an increased risk of cardiometabolic risk factors, but not all children carry a similar risk. Perinatal factors, i.e., gestational age (GA) and birth weight for GA, may affect the risk for metabolic complications. However, there are conflicting data whether the association between birth size and cardiometabolic risk factors is independent among children with obesity. Moreover, differential effects of GA and birth weight for GA on cardiometabolic risk factors in pediatric obesity are still unexplored. We aimed to investigate the association between birth weight for GA and cardiometabolic risk factors in children and adolescents with overweight or obesity and to assess whether the association is modified by prematurity. METHODS AND FINDINGS: We conducted a retrospective study of 2 cohorts, using data from the world's 2 largest registers of pediatric obesity treatment-The Swedish childhood obesity treatment register (BORIS) and The Adiposity Patients Registry (APV) (1991 to 2020). Included were individuals with overweight or obesity between 2 to 18 years of age who had data of birth characteristics and cardiometabolic parameters. Birth data was collected as exposure variable and the first reported cardiometabolic parameters during pediatric obesity treatment as the main outcome. The median (Q1, Q3) age at the outcome measurement was 11.8 (9.4, 14.0) years. The main outcomes were hypertensive blood pressure (BP), impaired fasting glucose, elevated glycated hemoglobin (HbA1c), elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and elevated transaminases. With logistic regression, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for each cardiometabolic parameter. All the analyses were adjusted for sex, age, degree of obesity, migratory background, and register source. In total, 42,760 (51.9% females) individuals were included. Small for GA (SGA) was prevalent in 10.4%, appropriate for GA (AGA) in 72.4%, and large for GA (LGA) in 17.2%. Most individuals (92.5%) were born full-term, 7.5% were born preterm. Median (Q1, Q3) body mass index standard deviation score at follow-up was 2.74 (2.40, 3.11) units. Compared with AGA, children born SGA were more likely to have hypertensive BP (OR = 1.20 [95% CI 1.12 to 1.29], p < 0.001), elevated HbA1c (1.33 [1.06 to 1.66], p = 0.03), and elevated transaminases (1.21 [1.10 to 1.33], p < 0.001) as well as low HDL (1.19 [1.09 to 1.31], p < 0.001). On the contrary, individuals born LGA had lower odds for hypertensive BP (0.88 [0.83 to 0.94], p < 0.001), elevated HbA1c (0.81 [0.67 to 0.97], p < 0.001), and elevated transaminases (0.88 [0.81 to 0.94], p < 0.001). Preterm birth altered some of the associations between SGA and outcomes, e.g., by increasing the odds for hypertensive BP and by diminishing the odds for elevated transaminases. Potential selection bias due to occasionally missing data could not be excluded. CONCLUSIONS: Among children and adolescents with overweight/obesity, individuals born SGA are more likely to possess cardiometabolic risk factors compared to their counterparts born AGA. Targeted screening and treatment of obesity-related comorbidities should therefore be considered in this high-risk group of individuals.

Pediatric obesity-Long-term consequences and effect of weight loss.

Childhood obesity is, according to the WHO, one of the most serious challenges of the 21st century. More than 100 million children have obesity today. Already during childhood, almost all organs are at risk of being affected by obesity. In this review, we present the current knowledge about diseases associated with childhood obesity and how they are affected by weight loss. One major causative factor is obesity-induced low-grade chronic inflammation, which can be observed already in preschool children. This inflammation-together with endocrine, paracrine, and metabolic effects of obesity-increases the long-term risk for several severe diseases. Type 2 diabetes is increasingly prevalent in adolescents and young adults who have had obesity during childhood. When it is diagnosed in young individuals, the morbidity and mortality rate is higher than when it occurs later in life, and more dangerous than type 1 diabetes. Childhood obesity also increases the risk for several autoimmune diseases such as multiple sclerosis, Crohn's disease, arthritis, and type 1 diabetes and it is well established that childhood obesity also increases the risk for cardiovascular disease. Consequently, childhood obesity increases the risk for premature mortality, and the mortality rate is three times higher already before 30 years of age compared with the normal population. The risks associated with childhood obesity are modified by weight loss. However, the risk reduction is affected by the age at which weight loss occurs. In general, early weight loss-that is, before puberty-is more beneficial, but there are marked disease-specific differences.

Effect of an interactive mobile health support system and daily weight measurements for pediatric obesity treatment, a 1-year pragmatical clinical trial.

BACKGROUND: Pediatric obesity lifestyle treatment is not always successful. Frequent clinical visits are of major importance to certify sufficient effect but are difficult due to the associated costs and the great demands on families. We hypothesized that an interactive digital support may reduce the need for frequent physical visits. The aim of the study was to assess 1-year weight outcome for patients using a digital support system compared with standard care. METHODS: An obesity lifestyle treatment with a digital support system was implemented in one clinic in Stockholm, Sweden. Measurements from a custom-made body scale without digits for daily home measurement of weights were transferred via Bluetooth to a mobile application, where BMI Z-score was calculated and presented graphically with an individualized weight loss target curve. An automatic transfer of data to the web-based clinic interface enables a close monitoring of treatment progress, and frequent written communication between the clinical staff and families via the application. One-year outcome was compared with a randomly retrieved, age and sex matched control group from the Swedish childhood obesity treatment register (BORIS), which received standard treatment at other clinics. Main outcome was change in BMI Z-score and missing data was imputed. RESULTS: 107 children were consecutively included to digi-physical treatment and 321 children to standard care. Age range 4.1-17.4 years (67% males). The attrition rate was 36% and 46% respectively, p = 0.08. After 1 year, the mean ± SD change in BMI Z-score in the treatment group was -0.30 ± 0.39 BMI Z-score units and in the standard care group -0.15 ± 0.28, p = 0.0002. The outcome was better for both sexes and all age groups in the digi-physical treated group. CONCLUSION: A digital support system with a personalized weight-loss target curve and daily weight measurements shared by the family and the clinic is more effective than a standard care childhood obesity treatment. GOV ID: NCT04323215.

Association of childhood obesity with risk of early all-cause and cause-specific mortality: A Swedish prospective cohort study.

BACKGROUND: Pediatric obesity is associated with increased risk of premature death from middle age onward, but whether the risk is already increased in young adulthood is unclear. The aim was to investigate whether individuals who had obesity in childhood have an increased mortality risk in young adulthood, compared with a population-based comparison group. METHODS AND FINDINGS: In this prospective cohort study, we linked nationwide registers and collected data on 41,359 individuals. Individuals enrolled at age 3-17.9 years in the Swedish Childhood Obesity Treatment Register (BORIS) and living in Sweden on their 18th birthday (start of follow-up) were included. A comparison group was matched by year of birth, sex, and area of residence. We analyzed all-cause mortality and cause-specific mortality using Cox proportional hazards models, adjusted according to group, sex, Nordic origin, and parental socioeconomic status (SES). Over 190,752 person-years of follow-up (median follow-up time 3.6 years), 104 deaths were recorded. Median (IQR) age at death was 22.0 (20.0-24.5) years. In the childhood obesity cohort, 0.55% (n = 39) died during the follow-up period, compared to 0.19% (n = 65) in the comparison group (p < 0.001). More than a quarter of the deaths among individuals in the childhood obesity cohort had obesity recorded as a primary or contributing cause of death. Male sex and low parental SES were associated with premature all-cause mortality. Suicide and self-harm with undetermined intent were the main cause of death in both groups. The largest difference between the groups lay within endogenous causes of death, where children who had undergone obesity treatment had an adjusted mortality rate ratio of 4.04 (95% CI 2.00-8.17, p < 0.001) compared with the comparison group. The main study limitation was the lack of anthropometric data in the comparison group. CONCLUSIONS: Our study shows that the risk of mortality in early adulthood may be higher for individuals who had obesity in childhood compared to a population-based comparison group.

Anxiety and depression in children and adolescents with obesity: a nationwide study in Sweden.

BACKGROUND: Anxiety and depression are more common in children with obesity than in children of normal weight, but it is unclear whether this association is independent of other known risk factors. Interpretation of results from previous studies is hampered by methodological limitations, including self-reported assessment of anxiety, depression, and anthropometry. The aim of this study was to investigate whether obesity increases the risk of anxiety or depression independently of other risk factors in a large cohort of children and adolescents, using robust measures with regard to exposure and outcome. METHODS: Children aged 6-17 years in the Swedish Childhood Obesity Treatment Register (BORIS, 2005-2015) were included (n = 12,507) and compared with a matched group (sex, year of birth, and area of residence) from the general population (n = 60,063). The main outcome was a diagnosis of anxiety or depression identified through ICD codes or dispensed prescribed medication within 3 years after the end of obesity treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox proportional models were adjusted for several known confounders. RESULTS: Obesity remained a significant risk factor for anxiety and depression in children and adolescents after adjusting for Nordic background, neuropsychiatric disorders, family history of anxiety/depression, and socioeconomic status. Girls in the obesity cohort had a 43% higher risk of anxiety and depression compared to girls in the general population (adjusted HR 1.43, 95% CI 1.31-1.57; p < 0.0001). The risk in boys with obesity was similar (adjusted HR 1.33, 95% CI 1.20-1.48; p < 0.0001). In sensitivity analyses, excluding subjects with neuropsychiatric disorders and a family history of anxiety/depression, the estimated risks in individuals with obesity were even higher compared with results from the main analyses (adjusted HR [95% CI]: girls = 1.56 [1.31-1.87], boys = 2.04 [1.64-2.54]). CONCLUSIONS: Results from this study support the hypothesis that obesity per se is associated with risk of both anxiety and depression in children and adolescents.

A novel interactive mobile health support system for pediatric obesity treatment: a randomized controlled feasibility trial.

BACKGROUND: In order to achieve improved weight status, behavioral pediatric obesity treatment is resource intensive. Mobile Health (mHealth) is more accessible than standard care but effective approaches are scarce. Therefore, the aim of this feasibility trial was to study trial design, mHealth usage, compliance, and acceptability of a novel mHealth approach in pediatric obesity treatment. METHODS: This six-month parallel two-arm feasibility trial took place at three pediatric outpatient clinics in Stockholm, Sweden. Participants, 5-12 years, starting obesity treatment were randomized to using an mHealth support system as an addition to standard care (intervention) or to standard care alone (control). The intervention included daily self-monitoring of weight transferred to a mobile application (app) used by parents, a website in which clinicians could track treatment progress, prespecified treatment goals for change in degree of obesity shown in the app and on the website, and text message interactions between clinicians and parents. The main outcome was description of feasibility. Height and weight were measured at baseline, three, and 6 months to explore changes in body mass index standard deviation score (BMI SDS). RESULTS: Of 40 children eligible for inclusion, 28 agreed to participate (54% girls) and were randomized to intervention (n = 15) or control (n = 13). Weight was measured at home regularly throughout the entire trial period by 12/15 children in the intervention group. Attendance at appointments were better in the intervention group (p = 0.024). Both parents and clinicians had a positive experience and found the mHealth support system accessible. At 6 months the intervention group had a greater reduction of 0.24 units in BMI SDS than standard care (- 0.23 vs. 0.01, p = 0.002). CONCLUSIONS: The mHealth support system was a feasible and innovative treatment approach which, in addition to standard care, generated better treatment results than standard care alone. Future research should evaluate the treatment effects over a longer follow-up time in a larger study sample. TRIAL REGISTRATION: This trial was retrospectively registered at ClinicalTrials.gov , ID: NCT03380598 , on November 8, 2017.

Promising results from an implemented treatment model for paediatric obesity.

AIM: To investigate the implementation of a plan of action for treatment of childhood obesity, and the effect after 2 years of treatment. METHODS: Children aged 6-12.9 years who started obesity treatment between 2008 and 2015 in a paediatric clinic in Stockholm County were included. The treatment model included staff education and support and group activities for parents and children separately followed by individual sessions to a multidisciplinary team. The main outcome was change in body mass index standard deviation score (BMI SDS), in comparison to a matched control group. RESULTS: In the intervention group, 1334 children (52% boys) with an average age of 9.3 years and BMI SDS of 2.7 and 3012 children in the control group were included. The intervention group decreased their BMI SDS more after two years compared with the control group, (-0.31 vs -0.23, P < .001). Younger age and higher BMI SDS at treatment initiation and families that completed the group sessions (all P < .001) had greater decreases in BMI SDS after 2 years. Sex did not affect the outcome. CONCLUSION: Even though the treatment in the control group was effective, the implementation of the action plan yielded a better treatment response compared with the control group.

The effect of weight loss and weight gain on blood pressure in children and adolescents with obesity.

OBJECTIVE: Obesity in childhood is a profound risk factor for hypertension, and weight loss has positive effects on blood pressure (BP). However, the expected effect size on BP from weight reduction in children with obesity is insufficiently described. Therefore, the aim was to investigate the association between changes of degree of obesity and BP levels. SUBJECTS: This prospective cohort study examined subjects receiving behavioral lifestyle modification treatment who were registered in the Swedish national registry for treatment of childhood obesity (BORIS). A total of 5279 obese subjects (51.3% boys) had repeated BP measurements. The average follow-up time was 32 months. Degree of obesity was expressed as BMI standard deviation score (SDS) and BP as BP SDS. RESULTS: The mean age at treatment initiation was 10.3 years. The prevalence of hypertensive BP was 15.3% for systolic and 5.5% for diastolic pressure. Both systolic and diastolic BP SDS decreased when a lower BMI SDS was achieved; systolic BP SDS decreased 0.41 [0.33-0.49] and diastolic BP SDS decreased 0.26 [0.20-0.32] per BMI SDS unit reduction. The impact of BMI SDS reduction on BP SDS was greater in subjects with hypertensive levels at treatment initiation, but behavioral modification was an insufficient treatment for 27% of them. Obesity treatment failure increased the risk of developing hypertensive levels; HR = 1.81 [1.38-2.37] (systolic BP) HR = 3.82 [2.34-6.24] (diastolic BP), per unit increase in BMI SDS. CONCLUSIONS: Weight loss is a key factor for hypertension prevention and treatment in children with obesity. However, its limited effect suggests that additional pharmacological antihypertensive treatment more readily should be considered.

Five-year outpatient programme that provided children with continuous behavioural obesity treatment enjoyed high success rate.

AIM: Results from long-time follow-up of obesity treatment in early childhood are lacking. We investigate long-term continuous behavioural childhood obesity treatment and factors of importance for treatment effect. METHOD: A five-year longitudinal retrospective controlled study of children aged five to 13 years in obesity treatment, divided into three groups depending on age at start of treatment. Outcome is presented as change in degree of obesity, body mass index standard deviation score (BMI SDS), change in weight status and decrease of ≥0.5 BMI SDS units, in relation to a age-matched obese comparison group. RESULTS: In total, 220 children (46% females) were included. After five years of treatment, the decrease in BMI SDS was significant in all age groups with the largest effect in age group 4-6 years. Compared to the comparison group (n = 369), the decline in BMI SDS was greater (p = 0.001). After five years of treatment, 48% of the patients were cured from their obesity and 72% reached a decline of 0.5 BMI SDS units. Age at start of treatment was the only factor affecting treatment efficacy. CONCLUSION: The ability to reach a significant weight loss in a paediatric outpatient clinic is promising through a long-term behavioural obesity treatment.

Blood sugar levels are higher in obese young children in Sweden than in Poland.

AIM: An elevated fasting glucose level is an early sign of metabolic dysfunction in obese children. This study compared fasting glucose levels in obese young children in Poland and Sweden. METHODS: We identified 109 obese children aged between two and 10 years from a Polish obesity register, with a mean BMI SDS (SD) of 3.72 (0.86). Each Polish child was matched by gender, age and degree of obesity, with ten children (n = 1090) from BORIS, the Swedish national childhood obesity treatment register. A group of 86 Swedish nonobese children served as controls. RESULTS: The mean fasting glucose values of the Polish, Swedish and nonobese cohorts were 4.73 (0.51) mmol/L, 4.92 (0.50) mmol/L and 4.56 (0.39) mmol/L, respectively. After adjusting for variables affecting fasting glucose, the mean glucose value of the Swedish obese children was 0.20 mmol/L higher than that of Polish obese children (p < 0.0001) and 0.41 mmol/L higher than in nonobese controls (p < 0.0001). CONCLUSION: Swedish obese young children had higher glucose levels than Polish obese young children. This suggests that Swedish obese children face a higher risk of the prediabetic stage impaired fasting glycaemia.

Height and Growth Velocity in Children and Adolescents Undergoing Obesity Treatment: A Prospective Cohort Study.

CONTEXT: Pediatric obesity affects endocrine conditions, which may alter growth. OBJECTIVE: This work aimed to investigate the effect of obesity severity and obesity treatment outcome on growth. METHODS: This prospective cohort study included children (aged 3-18 years) enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (1998-2020). Obesity was categorized as class I and class II obesity. Obesity treatment outcome was measured as body mass index (BMI) z score changes and categorized into good (BMI z score reduction of ≥0.25), intermediate, and poor (increasing BMI z score). Height for age z score, final height, and growth velocity were compared between class I and class II obesity. Further, the effect of obesity treatment outcome on growth velocity during 2-year follow-up was assessed. RESULTS: A total of 27 997 individuals (mean age 10.2 ± 3.6 years) were included. Individuals with class II obesity were on average taller than those with class I obesity during childhood. Among males, reduced growth spurt was observed in class I obesity, and even absent in class II obesity. Females exhibited a similar but less pronounced pattern. Good obesity treatment outcome yielded lower growth velocity at ages 3 to 9 years but higher growth velocity at ages 10 to 13 years compared to poor treatment outcome. CONCLUSION: Obesity severity is positively associated with height and growth velocity in childhood. A hampered growth spurt during puberty should be anticipated, particularly in adolescents with severe obesity. Therefore no difference in final height between class I and class II obesity is expected. Successful obesity treatment does not harm, but rather normalizes, the growth velocity pattern.

Evaluating probiotic efficacy on weight loss in adults with overweight through a double-blind, placebo-controlled randomized trial.

The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month double-blinded, randomized, placebo-controlled trial, followed by a 3-month open phase, was conducted at Karolinska Institutet, Sweden. The probiotic compound AB001 was tested at two doses (single and double) and compared with placebo during the blinded phase, and at triple dose during the open phase. Eighty-one volunteers, 18-45 years old, with overweight were included. The primary outcome was change in weight. Secondary outcomes were changes in; BMI, waist circumference, blood pressure, blood lipids, glucose metabolism, liver enzymes, vitamin levels, and bowel habits. After 3 months (n = 81), no difference in weight, BMI, waist circumference, blood pressure, or biomarkers were observed between the groups. Forty-five individuals continued with triple dose. The group with initial single dose decreased 0.93 ± 4.73 kg (p = 0.34), and the group with double dose initially decreased 1.93 ± 3.70 kg (p = 0.027). Reported changes in bowel habits and gastro-intestinal problems were similar for all doses. The results indicate that a long-term use of at least double dose AB001 may be more beneficial for weight loss than lower doses. However, in the double blinded phase, no differences between groups were found. The probiotic compound AB001 was well tolerated and can safely be used up to double dose for 90 days followed by triple dose for 90 days.Trial registration: Clinicaltrial.gov NCT04897698, registered on 21 May 2021.

Associations between cardiorespiratory fitness and cardiometabolic risk factors in children and adolescents with obesity.

It is unclear if associations between cardiorespiratory fitness (CRF) and cardiometabolic risk factors are independent of degree of obesity, in children with obesity. The aim of this cross-sectional study on 151 children (36.4% girls), 9-17 years, from a Swedish obesity clinic, was to investigate associations between CRF and cardiometabolic risk factors, adjusted for body mass index standard deviation score (BMI SDS), in children with obesity. CRF was objectively assessed with the Åstrand-Rhyming submaximal cycle ergometer test, and blood samples (n = 96) and blood pressure (BP) (n = 84) according to clinical routine. Obesity specific reference values for CRF were used to create CRF levels. CRF was inversely associated with high-sensitivity C-reactive protein (hs-CRP), independent of BMI SDS, age, sex, and height. The inverse associations between CRF and diastolic BP did not remain significant when adjusted for BMI SDS. CRF and high-density lipoprotein cholesterol became inversely associated when adjusted for BMI SDS. Independent of degree of obesity, lower CRF is associated with higher levels of hs-CRP, as a biomarker of inflammation, in children with obesity and regular assessment of CRF should be encouraged. Future research in children with obesity should investigate if low-grade inflammation decreases when CRF is improved.

Obesity in childhood, socioeconomic status, and completion of 12 or more school years: a prospective cohort study.

OBJECTIVES: Children with obesity achieve lower educational level compared with normal-weight peers. Parental socioeconomic status (SES) impacts both a child's academic achievement and risk of obesity. The degree to which the association between obesity and education depends on parental SES is unclear. Therefore, the primary aim is to investigate if individuals with obesity in childhood are less likely to complete ≥12 years of schooling, independently of parental SES. The secondary aim is to study how weight loss, level of education and parental SES are associated. DESIGN: Nationwide prospective cohort study. SETTING: Swedish national register data. PARTICIPANTS: Children aged 10-17 years, recorded in the Swedish Childhood Obesity Treatment Register, and aged 20 years or older at follow-up were included (n=3942). A comparison group was matched by sex, year of birth and living area (n=18 728). Parental SES was based on maternal and paternal level of education, income and occupational status. PRIMARY OUTCOME MEASURE: Completion of ≥12 years of schooling was analysed with conditional logistic regression, and adjusted for group, migration background, attention deficit disorder with or without hyperactivity, anxiety/depression and parental SES. RESULTS: Among those with obesity in childhood, 56.7% completed ≥12 school years compared with 74.4% in the comparison group (p<0.0001). High parental SES compared with low SES was strongly associated with attained level of education in both children with and without obesity, adjusted OR (aOR) (99% CI)=5.40 (4.45 to 6.55). However, obesity in childhood remains a strong risk factor of not completing ≥12 school years, independently of parental SES, aOR=0.57 (0.51 to 0.63). Successful obesity treatment increased the odds of completing ≥12 years in school even when taking parental SES into account, aOR=1.34 (1.04 to 1.72). CONCLUSIONS: Individuals with obesity in childhood have lower odds of completing ≥12 school years, independently of parental SES. Optimised obesity treatment may improve school results in this group.

Paediatric obesity treatment during 14 years in Sweden: Lessons from the Swedish Childhood Obesity Treatment Register-BORIS.

BACKGROUND: Treatment of paediatric obesity has been offered customarily and free of charge for more than 15 years in Sweden. The Swedish Childhood Obesity Treatment Register (BORIS) is a prospective register of children and adolescents undergoing obesity treatment. OBJECTIVES: To investigate how patient characteristics and treatment efficacy has changed over 14 years on a national scale. METHODS: All subjects in BORIS with data from 2004 until 2017 were included, n = 21 499. Outcomes were age and BMI SDS at treatment initiation, dropout rates and treatment outcome up to 3 years after treatment initiation. RESULTS: Age and BMI SDS at treatment initiation have decreased during the years (both P < .0001). Of the patients who started treatment before 2009, more than 80% had at least 1-year follow-up. This number has decreased to about 60% in 2017. Since 2004, no trend in improvement of treatment results was observed when evaluating change in either BMI SDS or proportion of obesity remission. There was no difference between the sexes. CONCLUSION: Although children in Sweden receive treatment at an earlier age, which is a major determinant of treatment success, and at a lower degree of obesity at treatment initiation, the effect of childhood obesity treatment on standard anthropometric measures has not improved over the investigated years.

Oral intake of mesoporous silica is safe and well tolerated in male humans.

BACKGROUND: Precisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated. OBJECTIVE: The aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans. DESIGN: This single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2). RESULTS: All participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred. CONCLUSION: Mesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns.

Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans.

Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic  α-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.

Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes.

Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.

Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes.

OBJECTIVE: Behavioral treatment of children suffering from hypothalamic obesity or uncomplicated obesity in combination with syndromes that aggravate this condition has proven to be ineffective. The combination of comorbidities and severe obesity lower the quality of these children's lives drastically. The present goal was to determine whether treatment with sibutramine has a beneficial effect on such children. DESIGN AND SUBJECTS: A double-blind, placebo-controlled, cross-over study (20 + 20 wk), followed by a 6-month open phase, was performed. The primary indicator of efficacy was the body mass index (BMI) sd score (SDS) value, which was analyzed using an ANOVA repeated-measures design [intention to treat (ITT)]. The 50 children (7-20 yr of age) involved included 22 with hypothalamic obesity and 28 with uncomplicated obesity plus aggravating syndromes. Forty-five patients completed the first phase, and 42 participated in the entire study. RESULTS: The group that initially received the placebo demonstrated an insignificant decrease (-0.06) in BMI SDS during this treatment but a significant decrease (-0.68; P < 0.001) when treated with sibutramine. The other group demonstrated a reduction in their BMI SDS of -0.72 during administration of sibutramine and a rebound of +0.43 when placed on the placebo (P < 0.001 in both cases). The response of children with hypothalamic obesity was also significant but was less pronounced than that of children with nonhypothalamic obesity. During the open phase, a continuous reduction in weight was observed. The treatment was tolerated well. CONCLUSION: The clinically and statistically significant weight reduction caused by sibutramine in this short-term study indicates that treatment of hypothalamic and syndromal obesity with this drug may be beneficial.

Childhood Obesity, Obesity Treatment Outcome, and Achieved Education: A Prospective Cohort Study.

PURPOSE: Childhood obesity represents a social burden. This study aims to investigate whether achieved educational level differs in young adults who have suffered obesity in childhood compared with the general population and to determine how obesity treatment influences achieved educational level. METHODS: This prospective cohort study includes subjects from the Swedish Childhood Obesity Treatment Registry (BORIS, n = 1,465) who were followed up after 20 years of age. They were compared with a randomly selected matched population-based group (n = 6,979). Achieved educational level was defined as ≥12 years in school (completers). Covariates include sex, migration background, and attention deficit disorders for both groups. Furthermore, age and degree of obesity at start of obesity treatment, treatment duration, and efficacy were analyzed in the obese cohort. RESULTS: In the obese cohort, 55.4% were school completers, compared with 76.2% in the comparison group (adjusted odds ratio [OR] = .42, p < .0001). Subjects with moderate obesity had a completion rate of 64.4%, compared with 50.9% among subjects with morbid obesity (adjusted OR = .57, p < .0001). Successful obesity treatment was associated with increased future educational level, compared with those experiencing no treatment effect (61.9% vs. 51.3% completers; adjusted OR = 1.4, p < .05). In children with attention deficit disorder, obesity was not an extra risk for not completing 12 or more years of schooling, p = .11. CONCLUSIONS: Obesity in childhood was associated with low educational level in early adulthood. Children and adolescents with obesity may require special support at school in addition to health care treatment to lose weight.