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.

Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention.

OBJECTIVE: To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification. SUMMARY OF BACKGROUND DATA: Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups. METHODS: Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention. RESULTS: During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3-6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8-9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61-2.98). CONCLUSIONS: Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.

BACKGROUND: Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity. METHODS: In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56. RESULTS: A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment. CONCLUSIONS: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).

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.

Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19.

BACKGROUND: The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. METHODS: Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). RESULTS: Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management. CONCLUSIONS AND CLINICAL IMPLICATION: We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840.

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.

Month of birth and the risk of developing type 1 diabetes among children in the Swedish national Better Diabetes Diagnosis Study.

AIM: Previous studies have reported an association between month of birth and incidence of type 1 diabetes. Using population-based data, including almost all newly diagnosed children with type 1 diabetes in Sweden, we tested whether month of birth influences the risk of type 1 diabetes. METHODS: For 8761 children diagnosed with type 1 diabetes between May 2005 and December 2016 in the Better Diabetes Diagnosis study, month of birth, sex and age were compared. Human leucocyte antigen (HLA) genotype and autoantibodies at diagnosis were analysed for a subset of the cohort (n = 3647). Comparisons with the general population used data from Statistics Sweden. RESULTS: We found no association between month of birth or season and the incidence of type 1 diabetes in the cohort as a whole. However, boys diagnosed before 5 years were more often born in May (p = 0.004). We found no correlation between month of birth and HLA or antibodies. CONCLUSION: In this large nationwide study, the impact of month of birth on type 1 diabetes diagnosis was weak, except for boys diagnosed before 5 years of age, who were more likely born in May. This may suggest different triggers for different subgroups of patients with type 1 diabetes.

Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

OBJECTIVES: Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D. METHODS: Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhüber classification. RESULTS: All of the 60 children with anti-tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. CONCLUSIONS: As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

Depression, anxiety, and suicidal ideation in young adults 5 years after undergoing bariatric surgery as adolescents.

PURPOSE: Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to explore symptoms of depression and anxiety in young adults over 5 years' follow-up after undergoing MBS. METHODS: Beck Depression Inventory-2 and the Beck Anxiety Inventory were used to assess symptoms of depression and anxiety in 62 patients 1, 2, and 5 years after having Roux-en-Y gastric bypass at 13-18 years of age. Mental health, eating-related problems, and weight outcomes were tested for association with suicidal ideation at the 5-year follow-up. RESULTS: At the 5-year follow-up, the mean score for depression was 11.4 (± 12.4), indicating minimal symptoms of depression. The mean score for anxiety was 12.82 (± 11.50), indicating mild anxiety symptoms. Still, several participants reported moderate or severe symptoms of depression (26%) and anxiety (32%). Women reported more symptoms than men (P = 0.03 and 0.04). No significant changes were found in self-reported symptoms of depression and anxiety between the 1-year and the 5-year follow-up (P = 0.367 and 0.934). Suicidal ideation was reported by 16% at the 5-year follow-up. Participants reporting suicidal ideation had lost significantly less excess weight than participants without suicidal ideation (P = 0.009). CONCLUSION: Five years after adolescent MBS, a substantial minority still struggles with mental health issues, and women are more burdened than men. Our results indicate an association between less optimal weight loss and suicidal ideation 5 years after MBS. The findings emphasize the importance of offering long-term follow-up and mental health treatment several years after MBS. LEVEL OF EVIDENCE: Level III, cohort study. CLINICAL TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT00289705). First posted February 10, 2006.

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.

Microalbuminuria and retinopathy in adolescents and young adults with type 1 and type 2 diabetes.

AIM: To estimate the occurrence of complications related to early-onset type 2 diabetes compared with type 1 diabetes. METHODS: All individuals registered in the Swedish Pediatric Quality Diabetes Register and the Swedish National Diabetes Register with type 2 diabetes diagnosis at 10 to 25 years of age between 1996 and 2014 (n = 1413) were included. As controls, individuals with type 1 diabetes were randomly selected from the same registers and were matched for age, sex, and year-of-onset (n = 3748). RESULTS: Of the adolescents with type 2 diabetes in the pediatric register, 7.7% had microalbuminuria and 24.6% had signs of retinopathy 5 years after diagnosis, whereas the adolescents with type 1 diabetes 3.8% had microalbuminuria and 19.2% had retinopathy. Among the young adults with type 2 diabetes from the adult diabetes register 10 years after diagnosis 15.2% had microalbuminuria and 39.7% retinopathy, whereas the young adults with type 1 diabetes 4.8% had microalbuminuria and 43.8% retinopathy. After adjustment for established risk factors measured over time in the whole combined cohort, individuals with type 2 diabetes had significantly higher risk of microalbuminuria with a hazard ratio (HR) of 3.32 (95% confidence interval, CI 2.86-3.85, P < .001), and retinopathy with a HR of 1.17 (95% CI 1.06-1.30, P 0.04). CONCLUSIONS: The prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1 diabetes, although prevalent in both groups. Early monitoring and more active treatment of type 2 diabetes in young individuals is required.

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.

Reference values and secular trends for cardiorespiratory fitness in children and adolescents with obesity.

AIM: To present specific reference values for cardiorespiratory fitness (CRF) in children with obesity and to analyse secular trends of CRF in the studied population. METHODS: Cardiorespiratory fitness, the maximal oxygen uptake (VO2 max), was estimated with the Åstrand-Rhyming submaximal bicycle test, in 705 Swedish children (356 girls, 8-20 years) with obesity according to the International Obesity Task Force (IOTF). Data were collected from 1999 to 2013. Secular trends, analysed with multiple linear regression, were adjusted for age, height and body mass index standard deviation score (BMI SDS). RESULTS: All children had low CRF compared with normal weight standards but there was a marked variability of CRF in children with obesity, which was possible to quantify with the developed obesity specific CRF reference values. The mean value of absolute VO2 max (L/min) increased with age and relative VO2 max (mL/kg/min) decreased with age in both boys and girls. There was a negative secular trend in both sexes (P < .001). CONCLUSION: These are the first obesity specific reference values of CRF in children enabling clinical evaluation in childhood obesity treatment. Cardiorespiratory fitness in children with obesity has declined the last decades, indicating that also within this vulnerable group physical activity has gone down.

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.

Insulin function in obese children within the low and high ranges of impaired fasting glycemia.

BACKGROUND/OBJECTIVE: Impaired fasting glycemia (IFG) reflects an intermediate hyperglycemia in the fasting state. Which fasting glucose level that actually is associated with impaired insulin-glucose homeostasis in children and adolescents with obesity is unknown. The aim of this study was to investigate how insulin and glucose homeostasis in children and adolescents with obesity in Sweden varies within different fasting glucose levels in the non-diabetic range. SUBJECTS: The subjects, n = 333, were divided into three groups based on their fasting glucose level. Normoglycemic range: up to 5.5 mmol/L (n = 268); the exclusive range the American Diabetes Association (ADA) has for IFG diagnosis: 5.6-6.0 mmol/L (n = 44); and IFG according to World Health Organization: 6.1-6.9 mmol/L (n = 21). The three groups were of similar age, degree of obesity, fasting insulin levels, sex, and migrant background distribution. METHODS: We used an insulin-modified frequent sample intravenous glucose tolerance test to study acute insulin response (AIR), insulin sensitivity (SI), and disposition index (DI) in children and adolescents with obesity. The main outcome measures were AIR, SI, and DI in three groups based on fasting glucose level. RESULTS: Fasting glucose levels ranging from 5.6 to 6.0 mmol/L were not associated with a lower AIR, SI, or DI compared with the normoglycemic range. However, glucose levels ranging from 6.1 to 6.9 mmol/L were associated with lower AIR and lower DI, but no statistical differences in SI were present. CONCLUSIONS: IFG in the exclusive ADA range was not associated with disturbed glucose metabolism. This suggests that IFG contributes to adverse metabolic profile in children differently to what has been described previously in adult obese populations.

Development of sleep patterns in children with obese and normal-weight parents.

AIM: To study the sleep development and sleep characteristics in children at different obesity risks, based on parental weight, and also to explore their weekday-weekend sleep variations and associated family factors. METHODS: A total of 145 children participating in a longitudinal obesity prevention project were included, of which 37 had normal-weight parents (low obesity risk), and 108 had overweight/obese parents (high obesity risk). Sleep diaries at ages 1 and 2 years were used to study sleep development in children at different obesity risks. Objectively assessed sleep using an accelerometer at 2 years of age was used to analyse weekday-weekend sleep variations. RESULTS: There was no difference in sleep development from age 1 to age 2 among children at different obesity risks, but more children in the high-risk group had prolonged sleep onset latency and low sleep efficiency. At 2 years of age, children in the high-risk group had more weekday-weekend variation in sleep offset (mean difference 18 min, 95% confidence interval (CI) 4-33 min), midpoint of sleep (mean difference 14 min, 95% CI 3-25 min) and nap onset (mean difference 42 min, 95% CI 10-74 min) than children in the low-risk group, after adjusting for other family factors. However, no difference could be detected between groups in weekday-weekend variation in sleep duration. CONCLUSIONS: Unfavourable sleep characteristics, as well as more variation in sleep schedules, have been observed in children at high obesity risk. While the differences were relatively small, they may reflect the unfavourable sleep hygiene in families at high obesity risk.

FAM13A and POM121C are candidate genes for fasting insulin: functional follow-up analysis of a genome-wide association study.

AIMS/HYPOTHESIS: By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). METHODS: Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes. RESULTS: Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R = -0.50, p = 5.6 × 10-7). Knockdown of FAM13A increased lipolysis by ~1.5-fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R = -0.22, p = 2.0 × 10-2), adipocyte insulin sensitivity (R = 0.28, p = 3.4 × 10-3) and adipose hyperplasia (R = -0.29, p = 2.6 × 10-2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25-50%, suggesting that POM121C is necessary for adipogenesis. CONCLUSIONS/INTERPRETATION: Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.

Weight Loss and Heart Failure: A Nationwide Study of Gastric Bypass Surgery Versus Intensive Lifestyle Treatment.

BACKGROUND: Associations of obesity with incidence of heart failure have been observed, but the causality is uncertain. We hypothesized that gastric bypass surgery leads to a lower incidence of heart failure compared with intensive lifestyle modification in obese people. METHODS: We included obese people without previous heart failure from a Swedish nationwide registry of people treated with a structured intensive lifestyle program and the Scandinavian Obesity Surgery Registry. All analyses used inverse probability weights based on baseline body mass index and a propensity score estimated from baseline variables. Treatment groups were well balanced in terms of weight, body mass index, and most potential confounders. Associations of treatment with heart failure incidence, as defined in the National Patient Register, were analyzed with Cox regression. RESULTS: The 25 804 gastric bypass surgery patients had on average lost 18.8 kg more weight after 1 year and 22.6 kg more after 2 years than the 13 701 lifestyle modification patients. During a median of 4.1 years, surgery patients had lower heart failure incidence than lifestyle modification patients (hazard ratio, 0.54; 95% confidence interval, 0.36-0.82). A 10-kg achieved weight loss after 1 year was related to a hazard ratio for heart failure of 0.77 (95% confidence interval, 0.60-0.97) in both treatment groups combined. Results were robust in sensitivity analyses. CONCLUSIONS: Gastric bypass surgery was associated with approximately one half the incidence of heart failure compared with intensive lifestyle modification in this study of 2 large nationwide registries. We also observed a graded association between increasing weight loss and decreasing risk of heart failure.