BACKGROUND:The early vascular impact of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study examined associations of steatosis in childhood and young adulthood with cardiovascular risk in adulthood. METHODS:Children with severe obesity were investigated for MASLD and cardiovascular risk, with 10-year follow-up. Hepatic steatosis was measured using proton magnetic resonance spectroscopy and cardiovascular risk by ultrasound carotid intima-media thickness (cIMT). Participants were categorised into four trajectory groups based on presence of steatosis in childhood and/or adulthood: 'absent', 'diminishing', 'adult-onset' and 'persistent'. Associations between steatosis (presence and change over time) and cIMT, and between childhood metabolic factors and cIMT progression, were evaluated. RESULTS:Of 52 participants, 46% had steatosis in childhood ('diminishing' or 'persistent'), and 46% in adulthood ('adult-onset' or 'persistent'). Childhood steatosis was not associated with cIMT in adulthood, whereas adulthood steatosis was independently associated with increased cIMT (mean difference 0.035 mm, 95% CI: 0.010-0.060 mm; p-adjusted = 0.008). Mean cIMT at follow-up increased progressively across steatosis trajectory groups; (adjusted p-for-trend = 0.003). Childhood steatosis was the only metabolic factor associated with cIMT progression (β = 0.006, p = 0.030). CONCLUSIONS:Hepatic steatosis in young adulthood is independently associated with increased cardiovascular risk, and childhood steatosis relates to cIMT progression, supporting early MASLD detection and prevention.
Large variability exists in outcome following Family-based treatment (FBT) for severe obesity in youth. In the present study, we aimed to expand our understanding of how mental health impacts FBT outcomes. In total, 90 participants (58.9% girls) 5.9-18.6 years (mean ± SD: 13.2 ± 3.1) were enrolled in a 17-session FBT-programme. Baseline mean percentage above the IOTF threshold for overweight (%IOTF25) was 146 ± 13, and Body Mass Index standard deviation score (BMIz) was 3.02 ± 0.52. Mental health predictors were assessed using the Self-Perception Profile for Children and the Child Behaviour Checklist. A multivariate multilevel Bayesian linear mixed-effects model with repeated measures was utilized to estimate the effects of mental health predictors on BMI outcomes. Average change in BMI during FBT was -3.80 (%IOTF25) and -0.08 (BMIz) units. Higher scores of Attention Deficit/Hyperactivity (ADH) Problems were associated with a smaller reduction in BMI (0.31 units for %IOTF25 (p = 0.02), 0.01 units for BMIz (p = 0.03) for each one-unit T-score increase on the ADH problem scale). Self-Worth, Emotional Dysregulation, Internalizing- and Externalizing problems were not associated with differences in BMI outcomes. Identifying children with higher ADH problems and incorporating additional family support strategies within FBT should be a focus for further treatment development.
BACKGROUND:Ultra-processed foods (UPFs) are linked to obesity and cognitive decline, but evidence on their association with executive function (EF) in children is limited. OBJECTIVE:To evaluate the UPFs-EF relationship in parent-child dyads with obesity seeking treatment. METHODS:Secondary analysis of the FRESH trial (NCT01197443) conducted at the University of California, San Diego. A total of 141 Parent-child dyads; parent age = 43 years (6.6), BMI = 32 (6.4); child age = 9.9 years (1.3), BMIz = 2.0 (0.3); 31% Hispanic, 44% White, 25% other completed anthropometric, digit span backward (DSB), stop signal task (SST) and Wisconsin Card Sorting Test (WCST), and dietary assessments. Linear regression models evaluated UPFs-EF associations, controlling for covariates. RESULTS:Parent-child associations were observed for energy β = 0.15, p = 0.024; total UPFs β = 0.20, p = 0.018; savoury snacks β = 0.28, p = 0.018; ultra-processed (UP) meat, β = 0.60, p < 0.001; and sweetened beverages β = 0.24, p = 0.023. Most UPFs-EF associations were null. In children, UP meat predicted lower DSB scores (β = -0.104, 95% CI [-0.197, -0.013], p = 0.013), and in parents, sweetened beverages predicted failed SST (β = 0.606, 95% CI [0.018, 1.210], p = 0.044). CONCLUSIONS:There were a few associations between UPFs intake and EF; however, most were nonsignificant. Future research should involve community samples and children across the weight spectrum.
BACKGROUND:Whether breastfeeding intensity, the relative amount of breastfeeding versus formula across the first year, relates to growth trajectories among infants exposed to gestational diabetes (GDM) in utero is unknown. OBJECTIVE:To identify growth trajectory patterns and associations with breastfeeding intensity among infants exposed to GDM. METHODS:SWIFT Offspring cohort (2009-2011) singleton, GDM-exposed infants (n = 435) born at a Kaiser Permanente Northern California hospital. Monthly summed lactation intensity ratio (sumLIR, proportion of breastfeeding versus overall feeds over 7 days). Latent class mixed models for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z-scores, and skinfold thicknesses (triceps, subscapular, and sum of skinfolds). Multinomial logistic regression related sumLIR to growth trajectories. RESULTS:A higher sumLIR throughout the first year was associated with lower odds of class membership in trajectories with accelerated growth patterns for WLZ from early infancy (1-mo OR: 0.11, 95% CI 0.02, 0.54) to 1 year (12-mo OR: 0.84, 95% CI 0.75, 0.95), as well as a lower likelihood of having accelerated WAZ growth after 6-months (12-mo OR: 0.91, 95% CI 0.84, 0.98), but not skinfold trajectory classes. CONCLUSIONS:Higher sumLIR was associated with more favourable growth trajectories, suggesting that continued breastfeeding, even when combined with infant formula, may benefit growth among GDM-exposed infants.
BACKGROUND:Previous research shows a longitudinal relationship between poor sleep and obesity in adolescents, highlighting the need to identify shared modifiable determinants to strengthen health-promoting interventions. The aim of this study was to investigate the determinants at 10 and 12 years associated with short sleep and body mass index percentile (BMIp) at 14 years, using data from the Growing Up in Scotland (GUS) study. METHODS:Secondary analyses were conducted using data from GUS Birth Cohort 1, sweeps 8-10 (10-14 years). Sleep duration, emotional wellbeing, physical activity, diet, screentime and risk-taking behaviours were main-carer or child-reported and BMIp was objectively measured. Block-wise linear regression analyses were used to examine associations with sleep duration and BMIp at age 14 years. Meaningful associations were defined as a ±10% difference (standardised β ≥ 0.10 or ≤ -0.10). RESULTS:Data from 4157 participants (50.2% male) were analysed. In adjusted models, having tried smoking and having tried alcohol at 12 years and being allowed to eat whenever the child wanted at 10 years were meaningfully associated with shorter sleep duration and higher BMIp at 14 years. Maternal BMI was meaningfully associated with BMIp only, while poorer emotional wellbeing and sugar-sweetened beverage consumption were meaningfully associated with shorter sleep only. CONCLUSIONS:Smoking and alcohol experimentation and less structured eating timing were identified as shared determinants of shorter sleep and higher BMIp in adolescence. These findings suggest that risk-taking behaviours and eating routines may be important targets for future research and health-promoting interventions addressing sleep and weight-related outcomes.
BACKGROUND:Formula feeding and having a mother with overweight are associated with overweight during infancy. OBJECTIVES:We sought to pilot test calibrated formula feeding guidance using age and weight specific intake recommendations to improve weight outcomes amongst at-risk infants. METHODS:Exclusively formula fed newborns with birthweight ≥ 50th percentile delivered to mothers with pre-pregnancy body mass index (BMI) ≥ 25 kg/m2 were randomised to intervention and usual care groups. At monthly visits from 1 to 5 months, mothers of intervention group infants with weight-for-length (WFL) ≥ 75th percentile were advised to give 10% less daily formula than required based upon sex, age and weight. The primary outcome was conditional weight gain (CWG) between birth and 6 months. Secondary outcomes included WFL z-score and overweight (WFL ≥ 95th percentile) at 6 months, as well as growth trajectory. RESULTS:Sixty infants were enrolled; 36 mothers (66.7%) had pre-pregnancy BMI ≥ 30. Seventeen (28.3%) withdrew before 6 months. At each assessment, a minority had WFL ≥ 75th percentile required to receive calibrated formula guidance. There were no group differences in CWG (intervention mean 0.27, 95% CI -0.20 to 0.75 vs. control mean -0.12, 95% CI -0.62 to 0.37; p = 0.25) or for secondary outcomes. CONCLUSIONS:Calibrated infant formula recommendations were not associated with growth outcomes. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT05104073 (registered October 11, 2021).
BACKGROUND:Real-world evidence of subsidised semaglutide in children with obesity is scarce. OBJECTIVES:To describe clinical outcomes (%IOTF30 change) in a nationwide cohort of Icelandic children prescribed subsidised semaglutide, describing outcomes across treatment settings and examining treatment response in children with and without neurodevelopmental disorders (ND). METHODS:Retrospective, population-based cohort study using longitudinal anthropometric measurements, March 20, 2021-June 6, 2025. Children aged ≥ 12 with grade 2 obesity were eligible for subsidised semaglutide under a universal reimbursement policy. Main outcomes were changes in %IOTF30 (BMI expressed as a percentage of the age- and sex-specific IOTF obesity threshold), modelled using piecewise linear mixed-effects regression. RESULTS:Among 113 participants (44% female; mean [SD] age 15.2 [2.0] years), pre-treatment %IOTF30 rose at 0.29 percentage points (pp)/month (95% CI, 0.26, 0.33). Semaglutide was associated with trajectory reversal at -0.86 pp/month (95% CI, -1.06 to -0.66); estimated reductions were 5.17 (95% CI, 3.98, 6.36) and 10.33 (95% CI, 7.96, 12.71) pp at six and 12 months. On-treatment slopes were numerically similar across settings but not interpretable as evidence of equivalent response. ND-status did not significantly modify treatment response among 56 Pediatric Obesity Center participants (interaction p = 0.83; underpowered). Overall, 63% achieved %IOTF30 reductions exceeding 10 pp. CONCLUSIONS:Semaglutide was associated with reversal of a longstanding upward weight trajectory in children with obesity. ND-status did not significantly modify treatment response; analysis was underpowered. Universal subsidisation policy enabled high treatment persistence and may inform reimbursement policy in other countries, though generalisability to settings without universal coverage remains uncertain.
BACKGROUND:In adolescents with obesity ≥ 1-year post-vertical sleeve gastrectomy (VSG), a pilot trial of liraglutide demonstrated a 4.3% BMI reduction. This secondary analysis evaluated energy intake changes (∆EI) and associations of ∆EI with oral glucose tolerance test (OGTT) outcomes and end-of-trial liraglutide plasma concentrations. METHODS:At baseline and after 4 months of liraglutide, participants completed a standardised buffet meal following a 2-h OGTT. Liraglutide plasma area under the curves (AUCs) were quantified using LC-MS/MS. RESULTS:Twenty-seven participants (18.1 ± 2.0 years; BMI: 40.4 ± 7.3 kg/m2) completed buffet meals at both visits. Mean energy intake decreased by 161.7 ± 264.3 kcal (p = 0.04) and food mass by 72.5 ± 123.4 g (p = 0.02), with proportional reductions in absolute macronutrient intake but no change in macronutrient distribution. Neither Liraglutide AUC (n = 17) nor OGTT outcomes were significantly associated with ∆EI or changes in body weight. CONCLUSIONS:In adolescents post-VSG treated with liraglutide, overall food intake decreased without significant changes in macronutrient composition.
BACKGROUND:Precision health represents an emerging paradigm in public health that uses individualised risk profiles to guide targeted prevention strategies. In childhood obesity, early-life determinants-such as genetics, growth patterns, family behaviours and environmental exposures-can inform interventions tailored to the specific needs of high-risk populations. Traditional universal approaches have shown limited long-term effectiveness, highlighting the need for more personalised prevention models. OBJECTIVE:This systematic review aimed to (1) evaluate the effectiveness of tailored and risk-based interventions for the primary prevention of childhood obesity in children aged 0-12 years, and (2) examine implementation characteristics and contextual factors influencing intervention outcomes. METHODS:Following PRISMA 2020 guidelines, we searched six databases (PubMed, Embase, Web of Science, Scopus, PsycINFO and CINAHL). The protocol was registered on PROSPERO (CRD420251103591). Eligible studies included RCTs, quasi-experimental, or pilot studies targeting obesity prevention using tailored or risk-stratified approaches in children aged 0-12, reporting anthropometric or behavioural outcomes. Data extraction and quality appraisal were conducted independently by two reviewers, with synthesis via narrative and thematic methods. RESULTS:Sixteen studies met inclusion criteria. Nine of 16 studies (56.3%) reported statistically significant reductions in BMI z-scores or obesity prevalence, with effect sizes ranging from -0.10 to -0.54 in BMI z-score units. Eleven studies (68.8%) observed significant improvements in dietary intake or physical activity behaviours. Culturally adapted, equity-focused interventions showed higher uptake and effectiveness. Key challenges included limited scalability, short follow-up periods and fidelity variability. CONCLUSIONS:Tailored, risk-based interventions hold promise for reducing early obesity risk and improving health behaviours. Precision health strategies, especially those that are family-centred and culturally sensitive, warrant further longitudinal evaluation to enhance equity and impact.
BACKGROUND:Sugar-sweetened beverages (SSBs) have been linked to obesity and metabolic dysfunction in youth; whereas the effects of 100% fruit juice, which is also high in free sugar, remain debated. OBJECTIVE:To compare metabolomic profiles of SSB versus 100% fruit juice intake across childhood and adolescence. METHODS:Data were from 593 youth in the EPOCH cohort collected during childhood (6-14 years) and adolescence (12-19 years). A food frequency questionnaire assessed total-energy-adjusted SSB and fruit juice intakes over the past week and fasting serum samples were assayed by untargeted metabolomics profiling. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrapping identified metabolites associated with each beverage at each visit. Metabolites consistently selected across visits were retained and compared. RESULTS:Mean (SD) SSB intake was 6.9 (4.9) and 5.2 (3.7) servings/week in childhood and adolescence, respectively, and mean fruit juice intake was 2.4 (2.6) and 1.7 (2.0) servings/week. Of 767 metabolites, 40 were associated with SSB intake and 39 were associated with fruit juice intake at both visits. Only three metabolites were associated with SSB and fruit juice intake (argininate, cortisone, quinate); all others were unique. Both beverages were linked to metabolites of amino acid, xenobiotic, lipid, and carbohydrate metabolism (10, 11, 8 and 1 metabolites, respectively, for SSB; 7, 8, 8 and 3 metabolites, respectively, for juice intake). CONCLUSIONS:SSB and 100% fruit juice intake are associated with largely distinct metabolomic profiles, suggesting some degree of beverage-specific metabolic effects in youth. Future studies are needed to replicate these findings, explore the role of common endogenous pathways and characterise mechanisms.
BACKGROUND:Telemedicine (TELE) may improve accessibility to paediatric obesity treatment, yet its effectiveness relative to face-to-face (FTF) care remains uncertain. OBJECTIVE:To compare the effects of a high-intensity, multidisciplinary TELE intervention with standard FTF care in children and adolescents with obesity. METHODS:Participants aged 10-18 years with obesity [body mass index (BMI) ≥ 2 standard deviations] were randomized to a 6-month TELE or FTF program in a tertiary-care centre paediatric obesity clinic. The TELE group received 30 weekly remote multidisciplinary consultations and a gamified step-monitoring application, along with three in-person visits. The FTF group attended six monthly in-clinic visits. The primary outcome was BMI z-score changes. Secondary outcomes included body composition, weight-related-quality-of-life (QOL), adherence, and satisfaction. RESULTS:One hundred participants were randomized 1:1 to TELE or FTF, of whom 65 completed the intervention (TELE n = 32; FTF n = 33). Baseline BMI z-scores were similar between groups (2.11 ± 0.32 vs. 2.11 ± 0.29). The reduction in BMI z-score was significantly greater in FTF than TELE (-0.16 ± 0.14 vs. -0.05 ± 0.15; p = 0.002), and any reduction was observed among 85% of FTF participants compared with 56% in TELE (p = 0.015). Body composition and QOL improved similarly in both groups, whereas satisfaction was higher in FTF. CONCLUSIONS:TELE-based care was less effective than FTF in reducing BMI z-score in children with obesity. Hybrid models integrating TELE with FTF visits warrant further investigation. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05700409.
BACKGROUND:Active commuting to and from school (ACS) is a feasible strategy to increase daily physical activity in children. Although ACS has been associated with favourable body composition and selected cardiometabolic markers, its association with specific ectopic fat depots remains unclear in paediatric populations. OBJECTIVE:To examine differences in specific fat depots and cardiometabolic risk factors between children who actively and passively commute to school. METHODS:Cross-sectional baseline data from 174 children (48.9% girls; mean age 10.8 ± 1.4 years) participating in the EFIGRO and MICROKID projects were analysed. ACS mode was self-reported using a validated questionnaire and classified as active or passive. Visceral adipose tissue, abdominal subcutaneous adipose tissue, intermuscular abdominal adipose tissue, hepatic fat, intrapancreatic fat, and lumbar spine marrow fat were assessed using magnetic resonance imaging. Cardiometabolic risk factors included blood pressure, triglycerides, high-density lipoprotein cholesterol, glucose, insulin, and insulin resistance estimated by the homeostasis model assessment. RESULTS:No significant differences were observed between active and passive commuters for any fat depot (all p ≥ 0.150) or cardiometabolic risk factors, including insulin resistance and the overall cardiometabolic risk score (all p ≥ 0.220). CONCLUSIONS:Active commuting to/from school was not associated with differences in ectopic fat depots, cardiometabolic risk factors, or insulin resistance in children.
BACKGROUND:The Dietary Inflammatory Index (DII) and its version adapted for children (C-DII) have emerged as promising tools to estimate the inflammatory potential of the diet and to enhance the understanding of the relationship between subclinical chronic inflammation and cardiometabolic risk during adolescence. OBJECTIVE:To investigate the associations of DII and C-DII with cardiometabolic risk indicators in adolescent students. METHODS:This cross-sectional study was conducted with 552 adolescents aged 10-17 years (66% girls; mean age: 13.6 ± 1.7 years). DII scores ranged from -1.34 to 5.04 (median: 2.62) and C-DII scores ranged from -1.99 to 4.39 (median: 1.96) and were categorised as anti-inflammatory diets (below the median) and pro-inflammatory diets (above the median). Outcomes included body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and blood pressure. Multilevel linear regression was applied. RESULTS:Adolescents with a pro-inflammatory diet (above the C-DII median) had a higher mean BMI (β = 0.97 kg/m2; 95% CI: 0.02; 1.92). Among girls, higher mean BMI values were observed for both DII (β = 1.29 kg/m2) and C-DII (β = 1.38 kg/m2). Among those > 14 years, pro-inflammatory diets were associated with higher BMI (β = 2.16 kg/m2), WC (β = 3.73 cm) and WHtR (β = 0.03) for both indices. No associations were observed with blood pressure. CONCLUSION:Pro-inflammatory diets were positively associated with higher adiposity, especially among girls and older adolescents. Early dietary interventions may help reduce lifetime cardiometabolic risk.
INTRODUCTION:Polygenic risk scores (PRS) stratify obesity risk in population cohorts, but their value within specialised paediatric obesity clinics-where genetic liability may already be saturated-remains unclear. METHODS:We analysed 246 European adolescents with overweight and obesity (mean ± SD age 13.3 ± 2.2 years; 51% female; BMI 31.6 ± 4.1 kg/m2) attending a tertiary clinic in Salzburg, Austria. BMI-PRS based on people with European ancestry (PGS000027) and two cardiometabolic PRS (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], type 2 diabetes [T2D]) were computed from Axiom-array genotypes. Distributions were compared with a population-based adult cohort from the same region (n = 2044). Associations with BMI, insulin resistance (HOMA-IR ≥ 2.5), alanine aminotransferase (ALT) and oral-glucose-tolerance parameters were examined by linear and logistic regression adjusted for age and sex. RESULTS:The adolescent cohort showed a right-shifted BMI-PRS distribution; the lowest quintile exceeded the adult mean (p < 0.001). Within the clinic sample, BMI-PRS neither correlated with BMI (r = -0.11; 95% CI -0.23 to 0.02) nor predicted other parameters investigated. PRS for HOMA-IR and T2D showed similarly null associations. CONCLUSIONS:In a genetically enriched clinical cohort, polygenic scores lose discriminatory power, delineating their optimal use for population screening rather than intra-clinic risk stratification. These data underscore the strong hereditary architecture of paediatric obesity and support context-specific application of precision-medicine tools.
PURPOSE:To explore the association between parental and child correct cognitions of the child's weight and child weight loss willingness and behaviours. METHODS:Data from the 2007-2020 NHANES database were used, focusing on overweight children aged 8-15 years with age- and sex-specific BMI ≥ the 85th percentile. Both parental and child correct cognitions of the child's weight were assessed by comparing subjective questionnaires with objective BMI measurements. Multivariable logistic regression was conducted. Path analysis was employed to confirm the effect of child correct cognition on the relationship between parental correct cognition and child weight loss willingness and behaviour. RESULTS:A total of 1383 overweight children were included. Parental correct cognition was independently associated with both child correct cognition and child weight loss willingness, but not with child weight loss frequency. Path analysis further demonstrated that child correct cognitions were linked to the relationship of parental correct cognitions on child weight loss willingness, establishing a significant path: 'Parental correct cognitions → Child correct cognitions → Child weight loss willingness → Child weight loss behaviour'. CONCLUSION:Among overweight children, parental correct cognitions of the child's weight do not directly relate to children's willingness. Instead, they were indirectly associated with child weight loss willingness and behaviour by shaping child correct cognitions of weight. This finding suggests that family weight management interventions should focus not only on parental correct cognitions but also on helping children establish objective correct cognitions of weight.
INTRODUCTION:Family mealtimes are promoted as a strategy to address childhood obesity; however, the joint associations of different mealtime elements with childhood obesity are not often considered. The current study investigated how mealtime family functioning and the nutritional quality of meals separately and jointly associate with childhood obesity. METHODS:Typical mealtimes for 273 children (M age = 5.9 years, SD = 0.7 years) were video-recorded. Observed mealtime family functioning, specifically mealtime structure and behaviour management, was coded from the video-recorded mealtimes. The nutritional quality of meals was assessed using the Healthy Meal Index (HMI). RESULTS:Logistic regression models indicated no independent associations between mealtime family functioning or nutritional quality of meals and child obesity status. However, the nutritional quality of meals moderated the association between mealtime structure and child obesity status (Interaction beta -0.06, SE 0.03; p = 0.04). Stratified analyses indicated that greater mealtime structure was associated with a higher likelihood of obesity among children served low-nutritional-quality meals (OR = 4.17, 95% CI 1.13-15.50, p = 0.03). CONCLUSIONS:Greater mealtime structure may be associated with an increased risk of childhood obesity when meals have low nutritional quality. Thus, various mealtime elements may interact in association with childhood obesity.
BACKGROUND:Infants with low birth weight are at increased risk of developing insulin resistance later in life. OBJECTIVES:To evaluate differences in adipocyte size during early childhood between infants with low birth weight and infants born appropriate for gestational age at full-term. METHODS:This cross-sectional study included 92 children (77 infants born appropriate for gestational age at full-term and 15 with low birth weight), aged 0.8-5.2 years, scheduled for surgery. Adipose tissue samples were obtained intraoperatively, fixed in osmic acid, and assessed for mean adipocyte diameter after adipocyte separation. RESULTS:Despite a similar body mass index, the low-birth-weight group had larger mean adipocyte diameters during early childhood than the term appropriate-for-gestational-age group (87.0 μm vs. 74.7 μm). Multiple regression analysis revealed that low birth weight and higher body mass index at surgery were significant determinants of larger mean adipocyte diameter (p < 0.001). Mean adipocyte diameter was not associated with haematological parameters, including insulin, adiponectin, and leptin levels. CONCLUSION:During early childhood, infants with low birth weight had larger adipocytes than infants born appropriate for gestational age at term. Further studies are required to determine whether this observation is associated with insulin resistance development later in life.
BACKGROUND:Evidence for the role of health behaviour and lifestyle treatment (HBLT) on the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in paediatric obesity is limited. OBJECTIVES:To assess the role of HBLT on the effectiveness of GLP-1RAs in youth with obesity. METHODS:Patients aged 8-18 years with obesity (n = 51) receiving liraglutide were retrospectively divided into continuers (ongoing liraglutide treatment), discontinuers, or switches to semaglutide or metabolic-bariatric surgery. All were offered multidisciplinary HBLT and consecutively allocated to either high-frequency (HF) HBLT (≥ 26 contact hours/year) or low-frequency obesity medication (OM)-specific HBLT (9 contacts of 0.5 h/year). RESULTS:After 9.7 ± 6.6 months, a BMI reduction of ≥ 5% and ≥ 10% was observed in 37.3% and 13.7%, respectively. Relative change in BMI was higher in continuers compared to discontinuers (-6.7% ± 7.5% vs. -0.7% ± 5.1%, p = 0.03). Whereas 39.2% of patients continued liraglutide, 33.3% discontinued, mainly due to gastrointestinal symptoms. 27.4% of patients switched treatment to semaglutide or underwent surgery. Patients with combined HBLT and liraglutide had markedly higher odds of continuation (OR 18.5, 95% CI 2.0-929.8, p < 0.01) and greater reductions in BMI, which was by trend higher with OM-HBLT compared to HF-HBLT (BMI change -6.9% ± 7.2% vs. -4.0% ± 6.6%). CONCLUSIONS:GLP-1RAs were effective in the real-world treatment of paediatric obesity. HBLT appears to be essential to increase persistence and efficacy of GLP-1RAs.
OBJECTIVE:Non-syndromic monogenic obesity, caused by defects in the leptin-melanocortin pathway, presents with early-onset severe obesity and hyperphagia, but genotype-phenotype and metabolic correlations across different genetic forms remain unclear. METHODS:In this multicentre retrospective cohort study, individuals with biallelic (likely) pathogenic variants in LEP, LEPR, POMC, PCSK1, MC4R, ADCY3, and monoallelic (likely) pathogenic MC4R variants were recruited from 23 paediatric endocrinology centres across Türkiye. Anthropometric, clinical, metabolic data, including HOMA-IR and SPISE index, systematically applied across different monogenic obesity subtypes, were collected using a standardised case record form. RESULTS:A total of 130 individuals (49% female; median age 10.0 years) were included. Biallelic LEPR (n = 47) and monoallelic MC4R (n = 49) variants were the most frequent causes, followed by biallelic POMC (n = 13) and MC4R (n = 11) variants. Individuals with LEP, LEPR, and biallelic MC4R variants had higher BMI-SDS than those with POMC and monoallelic MC4R variants (p < 0.0001). SPISE index differed across groups (p = 0.0051), with lower values in biallelic LEPR and MC4R compared with monoallelic MC4R variants. Within LEPR, individuals carrying 'double homozygous' missense variants showed poorer metabolic outcomes independent of BMI-SDS (p < 0.05). POMC deficiency showed a similar phenotype to monoallelic MC4R, with later obesity onset, lower BMI-SDS, and a more favourable metabolic profile. Bone age was advanced in LEPR compared to POMC, biallelic and monoallelic MC4R variants (p = 0.013) and bone age-adjusted height-SDS was lower than non-adjusted height-SDS (p = 0.004), indicating impaired growth when adjusted for skeletal maturation. CONCLUSION:Biallelic LEPR, particularly those with double homozygous missense variants, and MC4R variants represent the most metabolically adverse forms of monogenic obesity, extending current evidence beyond BMI-based risk stratification. In LEPR, advanced bone age may contribute to impaired growth. These data provide a comprehensive genotype-phenotype characterisation in a genetically homogeneous population and emphasise the importance of early diagnosis for risk stratification.
INTRODUCTION:Obesity disproportionately affects children from socioeconomically disadvantaged backgrounds. This study assessed the effectiveness of the Feel4Diabetes intervention on weight outcomes among children from low socioeconomic settings. METHODS:Feel4Diabetes was a randomised pragmatic trial implemented in real-world school and community settings across Europe. Using a two-stage screening procedure, families were recruited and categorised as either 'all families' or 'high-risk families'. The intervention included a 2-year school-based health promotion for all families and additional counselling for high-risk families. Weight improvement was defined as a reduction of ≥ 0.2 BMI z-score units among children with overweight/obesity. Multiple logistic regressions identified predictors of improvement. RESULTS:Data from 2710 children from high-risk families and 7625 children from all families were analysed. After 2 years, a higher proportion of children from high-risk families in the intervention group reduced their BMI z-score compared to the control group (p = 0.002). Children from non-high-risk families showed only a marginal improvement. Multivariate analyses identified predictors of improvement: randomisation in the intervention group (OR = 1.46; 95% CI: 1.14-1.87), baseline obesity (OR = 1.55; 95% CI: 1.16-2.08), residence in LMICs (OR = 2.33; 95% CI: 1.65-3.30) or HICs facing economic crisis (OR = 2.12; 95% CI: 1.54-2.91), and reported financial difficulties (OR = 1.36; 95% CI: 1.06-1.74). Interestingly, maternal obesity was positively associated with BMI z-score improvement (OR = 1.31; 95% CI: 1.03-1.68), while higher maternal education was inversely related (OR = 0.64; 95% CI: 0.41-0.99). CONCLUSION:These findings underscore the importance of equity-oriented, long-term interventions addressing both behavioural and structural determinants of obesity.
