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.

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.

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.

Physical activity in early childhood: a five-year longitudinal analysis of patterns and correlates.

BACKGROUND: Knowledge on longitudinal patterns and related factors of young children's physical activity (PA) is still scarce. Therefore, the aim of this study was to examine patterns and changes of accelerometer-measured PA over time in two to six-year-old children. Furthermore, the aim was to investigate if parental PA, socioeconomic status, sex, weight status, and motor skills are related to child PA over time, using prospective cohort data from a clustered randomized controlled trial. METHODS: One hundred and six children (52% girls) and their parents had PA measured yearly from age two to six with an Actigraph GT3X. The actigraph was worn on the non-dominant wrist for one week; anthropometric data and motor skills, as well as background information, was collected simultaneously. The outcome was counts per minute from the vector magnitude, and linear mixed-effect models were used to answer the research questions. RESULTS: Among the children, accelerometer-measured PA increased on average by 11% per year from two years of age (mean 3170 cpm (3007-3334 95% CI)) onwards to six years of age (mean 4369 cpm (4207-4533 95% CI)). From three years of age, children were more active on weekdays than on weekend days. The rate of difference varied across low, medium, and highly active children (based on tertiles). No significant differences in weekdays/weekend PA among the lowest active children was found. Despite this, they were still significantly less active on weekend days than the most active children. Maternal, but not paternal PA was found to be significantly positively related to child PA over time, with a medium to large effect size. But no significant relationships were found between child PA and sex, weight status, or socioeconomic status. CONCLUSIONS: PA increased on average with 11% per year, similarly for boys and girls. From three years of age children were more active during weekdays than weekend days. These results indicate that child PA benefits from active stimulation by parents and care takers already from early ages. It is important to identify attributes of possible intervention designs for weekend days for families with young children as well as characterize the least active children. TRIAL REGISTRATION: Early STOPP was prospectively registered in the clinical trials registry: clinicaltrials.gov , ID NCT01198847.

Risk and protective factors of non-alcoholic fatty liver disease in paediatric obesity: A nationwide nested case-control study.

Not all children with obesity carry a similar risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of obesity severity, metabolic risk parameters, and obesity treatment outcome on later risk of NAFLD in paediatric obesity. We conducted a nested case-control study of children and adolescents enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (2001-2016). NAFLD was ascertained from the National Patient Register. Five controls per case were matched by sex and age at index date and at the obesity treatment initiation. Seventy-six pairs (n cases = 76, n controls = 241) were included in the analysis (29% females, mean age at obesity treatment initiation was 10.8 ± 3.07 years). Mean age of NAFLD diagnosis was 14.2 ± 3.07 years. The risk for NAFLD increased with severe obesity (odds ratio [OR]: 3.15, 95% confidence interval [CI]: 1.69-5.89), impaired fasting glucose (OR: 5.29, 95% CI: 1.40-20.06), high triglycerides (OR: 2.33, 95% CI: 1.22-4.43) and weight gain (OR: 4.67, 95% CI: 1.51-14.49 per body mass index standard deviation score [BMI SDS] unit). Relative weight loss of at least 0.25 BMI SDS units reduced NAFLD risk independently of other risk factors (OR: 0.09, 95% CI: 0.01-0.56). Severe obesity, impaired fasting glucose and high triglycerides are risk factors for future NAFLD in paediatric obesity. Successful obesity treatment almost eliminates the risk for NAFLD independently of obesity severity, IFG and high triglycerides.

Prevalence of increased transaminases and its association with sex, age, and metabolic parameters in children and adolescents with obesity - a nationwide cross-sectional cohort study.

BACKGROUND: Childhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters. METHODS: Individuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27-51 U/L (males) and 23-43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis. RESULTS: Among 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29-1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02-1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35-1.70; class III obesity OR, 99% CI: 2.17, 1.66-2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51-2.20; class III obesity OR, 99% CI 3.38, 2.71-4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group. CONCLUSIONS: The risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT.

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.

High estimated prevalence of bariatric surgery in young adults treated for pediatric obesity.

BACKGROUND: Despite the modest effects of behavioral treatment on obesity in adolescence, bariatric surgery is rarely performed. Obesity often persists from childhood to adulthood, but it is not known how many individuals proceed with bariatric surgery in young adulthood. OBJECTIVE: The aim of this study was to determine what proportion of individuals who received pediatric behavioral obesity treatment subsequently underwent bariatric surgery in early adulthood, and to identify predictors thereof. SETTING: National registries, Sweden. METHODS: In this prospective cohort study, the Swedish Childhood Obesity Treatment Register was linked to several national registers. RESULTS: The childhood obesity cohort included 6502 (45% females) with a median age at follow-up of 21.7 years (interquartile range [IQR] 5.2). Of these, 8.2% underwent bariatric surgery at a median age of 20.9 years (IQR 4.2). The estimated cumulative incidence of bariatric surgery at age 30 was 21.5%. Obesity-related co-morbidities were identified in 31.7% before bariatric surgery in the childhood obesity cohort. Predictors of bariatric surgery were female sex, high body mass index standard deviation score (BMI SDS) at the start and end of treatment, poor treatment response, as well as own or parental cardiometabolic disease. CONCLUSIONS: More than a fifth are estimated to undergo bariatric surgery in early adulthood, despite having received pediatric behavioral obesity treatment. Our results indicate that for many children, behavioral treatment is insufficient in reducing obesity and preventing obesity-related co-morbidity. Therefore, it is reasonable to assume that more effective treatment of adolescents with severe obesity, including more rigorous behavioral support and pharmacologic treatment, but also more frequent use of bariatric surgery, would benefit this group of patients.

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.

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.

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.

Patterns and correlates of objectively measured physical activity in 3-year-old children.

BACKGROUND: To increase the knowledge about physical activity (PA) patterns and correlates among children under the age of 4, there is a need for study's using objective measurements. The aim of this study was therefore to investigate if objectively measured PA among 3-year-old children differed between day of week and time of day and whether it correlated to child weight status and sex as well as parental weight status and education. METHODS: Totally 61 children (51% girls) aged 3, participating in Early Stockholm Obesity Prevention Project were included. PA was measured with a tri-axial accelerometer (ActiGraph GT3X+) worn on the non-dominant wrist for one week. The main outcome was average PA expressed as counts per minute from the vector magnitude. PA and demographics/family-related factors were collected at baseline and at age 3. To analyze the results simple linear regression, ANOVA and paired t-tests were performed. RESULTS: The mean number of valid days was 6.7 per child. The children were more active on weekdays than weekends (p < 0.01) and the hourly pattern differed over the day with children being most active midmorning and midafternoon (p = 0.0001). Children to parents with low education were more active (p = 0.01) than those with highly educated parents. No differences in PA by child weight status, sex nor parental weight status were found. CONCLUSIONS: PA in 3-year-old children was lower during weekends than weekdays and varied over the day. Boys and girls had similar PA patterns, these patterns were independent of child or parental weight status. Children to parents with low education were more active than their counterparts. The fact that PA differed between weekdays and weekends indicates that PA might be affectable in 3-year-old children.

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.

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.

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.

Relation of the degree of obesity in childhood to adipose tissue insulin resistance.

AIMS: In this study, we investigated whether adipose tissue insulin resistance (IR) is affected by the degree of obesity during the fasting and post-prandial state, independent of glucose tolerance among obese children and adolescents. We also tested whether systemic subclinical inflammation is associated with adipose tissue IR. METHODS: Subjects were recruited to the Yale Pathophysiology of Type 2 Diabetes in Youth Study (NCT01967849). An oral glucose-tolerance test was performed to establish glucose-tolerance status and blood samples were drawn for measurement of free fatty acids (FFAs), to calculate the area under the curve (AUC) of FFA. Adipose tissue insulin resistance was calculated as the product of insulin and FFA concentrations. RESULTS: In total, 671 children and adolescents (58.6% females) were included with a mean age of 13.3(2.7) years and BMI Z score of 2.45(0.31). The degree of obesity emerged as an independent predictor of both fasting and post-prandial adipose IR, p < 0.0001. Higher degree of obesity was associated with greater AUC FFA (lower suppression) compared to lower degree of obesity, p = 0.01. Furthermore, higher levels of IL-6 were positively associated with post-prandial adipose tissue IR, p = 0.02. CONCLUSIONS: The degree of obesity in childhood and adolescence is strongly associated with adipose tissue IR independent of glucose tolerance. This is reflected not only in calculated indices of adipose IR but also in lower suppression of FFAs during the OGTT regardless of glucose tolerance or fasting adipose tissue IR. Furthermore, markers of subclinical inflammation such as IL-6 are associated with adipose tissue IR, independent of other factors.