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.

Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes.

OBJECTIVE: To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk. RESEARCH DESIGN AND METHODS: A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used. RESULTS: Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P < 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P < 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P < 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children <9 years of age. CONCLUSIONS: The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.

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.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

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.

Child and adolescent obesity.

The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joined-up policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.

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.

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.

Long-term changes in dietary intake and its association with eating-related problems after gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is an established, effective treatment for severe adolescent obesity. Long-term dietary intake and the relationship to eating-related problems are scarcely evaluated in this population. OBJECTIVES: Assess changes in dietary intake in adolescents after RYGB and explore associations between dietary intake and eating-related problems. SETTING: Multicenter study in Swedish university hospitals. METHOD: Diet history, binge eating scale (BES), and Three-Factor Eating Questionnaire were assessed preoperatively and 1, 2, and 5 years after RYGB in 85 adolescents (67% female) aged 16.5 ± 1.2 years with a body mass index (BMI) of 45.5 ± 6.0 kg/m2 and compared with control individuals at 5 years. RESULTS: Five-year BMI change was -28.6% ± 12.7% versus +9.9% ± 18.9% in RYGB patients versus control individuals (P < .001). Through 5 years, RYGB adolescents reported reduced energy intake, portion size of cooked meals at dinner, and milk/yoghurt consumption (P < .01). The BES scores were 9.3 ± 8.3 versus 13.4 ± 10.5 in RYGB patients versus control individuals (P = .04). Association between BES score and energy intake was stronger in control individuals (r = .27 versus r = .62 in RYGB patients versus control individuals, P < .001). At 5 years, lower energy intake was associated with greater BMI loss in all adolescents (r = .33, P < .001). Higher scores in BES and uncontrolled and emotional eating were associated with higher energy intake, cooked meals, candies/chocolates, cakes/cookies, desserts, and sugary drinks (r > .23, P < .04) and lower intake of fruits/berries (r = -.32, P = .044). A higher score in cognitive restraint was associated with a higher intake of cereals and fruits/berries (r > .22, P < .05) and a lower intake of sugary drinks (r = -.24, P < .03). CONCLUSION: To support optimization of long-term outcomes in adolescent RYGB patients, it is important to provide management strategies to reduce energy intake. Monitoring eating-related problems could identify potential individuals at risk of poor weight loss and to initiate treatment interventions.

Recurrent massive hemoptysis from distal pulmonary pseudoaneurysms complicating invasive aspergillosis in a teenager.

Invasive pulmonary aspergillosis in children rarely complicates life-threatening massive hemoptysis. Here, we report the case of a 15-year-old girl with acute lymphoblastic leukemia who was hospitalized for fever and medullary aplasia 1 month after beginning chemotherapy for invasive pulmonary aspergillosis. Despite voriconazole and caspofungine treatment, excavation of some lesions caused a unilateral small pneumothorax and bilateral pleural effusion, justifying intensive care management. The massive hemoptysis that occurred on day 23 was complicated with heart failure, and the patient was promptly resuscitated. Fibroscopy and computed tomography angiography (CTA) did not reveal the origin or cause of the bleeding. A second massive bleeding event occurred on day 32, and heart failure resolved after 10min of low flow. A new CTA showed 2 pseudoaneurysms of the subsegmental pulmonary arteries that were treated with embolization. Sedation was gradually decreased owing to improvement in respiratory status, but the patient did not regain consciousness because of deep brain sequelae. A limitation of care was decided upon, and the patient died in the following weeks. Massive hemoptysis is a rare life-threatening complication of invasive pulmonary aspergillosis, especially in children. Pulmonary artery pseudoaneurysms are unusual and should be detected as soon as possible to guide therapy. Intensive care management should be followed by embolization if the patient is stable; otherwise, surgery is indicated, ideally after identifying the source of bleeding by CTA or bronchoscopy. Early CTA follow-up can be proposed if the source of bleeding is still unknown as pseudoaneurysms can appear or grow rapidly.

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.

Comparison of Sleeve Gastrectomy vs Intensive Lifestyle Modification in Patients With a BMI of 30 to Less Than 35.

Importance: There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). Objective: To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. Design, Setting, and Participants: This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. Interventions: Sleeve gastrectomy or intensive lifestyle treatment. Main Outcomes and Measures: Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events retrieved from the National Patient Register, Prescribed Drug Register, and Cause of Death Register as well as the Scandinavian Obesity Surgery Registry and the Itrim health database. Data were analyzed from December 1, 2021 until May 31, 2022. Results: The study included 1216 surgery patients and 2432 lifestyle participants with similar mean (SD) BMI (32.8 [1.4] vs 32.9 [1.4]), mean (SD) age (42.4 [9.7] vs 42.6 [12.7] years), and sex (1091 [89.7%] vs 2191 [90.1%] women). Surgery patients had greater 1-year weight loss compared with controls (22.9 kg vs 11.9 kg; mean difference, 10.7 kg; 95% CI, 10.0-11.5 kg; P < .001). Over a median follow-up of 5.1 years (IQR, 3.9-6.2 years), surgery patients had a lower risk of incident use of diabetes drugs (59.7 vs 100.4 events per 10 000 person-years; hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02) and greater 2-year diabetes drug remission (48.4% vs 22.0%; risk difference 26.4%; 95% CI, 11.7%-41.0%; P < .001), but higher risk for substance use disorder (94 vs 50 events per 10 000 person-years; HR, 1.86; 95% CI, 1.30-2.67; P < .001) and self-harm (45 vs 25 events per 10 000 person-years; HR, 1.81; 95% CI, 1.09-3.01; P = .02). No between-group difference in occurrence of major cardiovascular events was observed (23.4 vs 24.8 events per 10 000 person-years; HR, 0.96; 95% CI, 0.49-1.91; P = .92). Conclusions and Relevance: In this cohort study, compared with intensive nonoperative obesity treatment, sleeve gastrectomy in patients with class 1 obesity was associated with greater weight loss, diabetes prevention, and diabetes remission but a higher incidence of substance use disorder and self-harm.

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.

Response to Induction Therapy in Pediatric Hodgkin's Lymphoma: Performance of First-Order Texture Parameters of CT Images.

Objectives: The aim of this study was to examine whether texture analysis features on pretreatment contrast-enhanced CT images could predict adequate response (AR) or inadequate response (IR) after two cycles of chemotherapy in pediatric Hodgkin's lymphoma (PHL). Materials and methods: This retrospective single-center study included 32 children and adolescents with HL. Texture analysis was independently performed by two radiologists using pretreatment CT scans. The mean gray level, standard deviation, entropy, kurtosis, and skewness were derived from pixel distribution histograms before and after spatial filtration ranging from two (fine texture) to six (coarse texture). Interobserver reliability was studied using interobserver correlation coefficients (ICCs) to select texture parameters. Relationships between early response assessment (ERA) to induction therapy and associated factors were studied using Student's t-tests and a lasso penalized logistic regression analysis. Results: Of the 32 patients, IR was observed in 13 and AR in 19. Inter-reader agreement was good to excellent (ICC > 0.75) for all parameters except skewness and kurtosis without filtration and at spatial scale filtration (SSF) = 2. These parameters were excluded from the analysis. The t-test identified only entropy at SSF = 2 (p value = 0.039) as a potential predictor of ERA. No parameters were significantly associated with ERA, according to a lasso penalized logistic regression. Conclusion: No textural parameters were identified as predictors of ERA after two cycles of chemotherapy in PHL.

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.

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.

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.

Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement.

The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver disease (MAFLD). Similarities, distinctions, and differences exist in the causes, natural history, and prognosis of fatty liver diseases in children compared with adults. In this Viewpoint we, an international panel, propose an overarching framework for paediatric fatty liver diseases and an age-appropriate MAFLD definition based on sex and age percentiles. The framework recognises the possibility of other coexisting systemic fatty liver diseases in children. The new MAFLD diagnostic criteria provide paediatricians with a conceptual scaffold for disease diagnosis, risk stratification, and improved clinical and multidisciplinary care, and they align with a definition that is valid across the lifespan.

The KAG motif of HLA-DRB1 (ß71, ß74, ß86) predicts seroconversion and development of type 1 diabetes.

BACKGROUND: HLA-DR4, a common antigen of HLA-DRB1, has multiple subtypes that are strongly associated with risk of type 1 diabetes (T1D); however, some are risk neutral or resistant. The pathobiological mechanism of HLA-DR4 subtypes remains to be elucidated. METHODS: We used a population-based case-control study of T1D (962 patients and 636 controls) to decipher genetic associations of HLA-DR4 subtypes and specific residues with susceptibility to T1D. Using a birth cohort of 7865 children with periodically measured islet autoantibodies (GADA, IAA or IA-2A), we proposed to validate discovered genetic associations with a totally different study design and time-to-seroconversions prior to clinical onset of T1D. A novel analytic strategy hierarchically organized the HLA-DRB1 alleles by sequence similarity and identified critical amino acid residues by minimizing local genomic architecture and higher-order interactions. FINDINGS: Three amino acid residues of HLA-DRB1 (ß71, ß74, ß86) were found to be predictive of T1D risk in the population-based study. The "KAG" motif, corresponding to HLA-DRB1×04:01, was most strongly associated with T1D risk ([O]dds [R]atio=3.64, p = 3.19 × 10-64). Three less frequent motifs ("EAV", OR = 2.55, p = 0.025; "RAG", OR = 1.93, p = 0.043; and "RAV", OR = 1.56, p = 0.003) were associated with T1D risk, while two motifs ("REG" and "REV") were equally protective (OR = 0.11, p = 4.23 × 10-4). In an independent birth cohort of HLA-DR3 and HLA-DR4 subjects, those having the "KAG" motif had increased risk for time-to-seroconversion (Hazard Ratio = 1.74, p = 6.51 × 10-14) after adjusting potential confounders. INTERPRETATIONS: DNA sequence variation in HLA-DRB1 at positions ß71, ß74, and ß86 are non-conservative (ß74 A→E, ß71 E vs K vs R and ß86 G vs V). They result in substantial differences in peptide antigen anchor pocket preferences at p1, p4 and potentially neighboring regions such as pocket p7. Differential peptide antigen binding is likely to be affected. These sequence substitutions may account for most of the HLA-DR4 contribution to T1D risk as illustrated in two HLA-peptide model complexes of the T1D autoantigens preproinsulin and GAD65. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases and the Swedish Child Diabetes Foundation and the Swedish Research Council.