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Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of obesity management on 186 children and adolescents in a clinical setting. Using mass spectrometry-based lipidomics, we report an increase in ceramides, alongside a decrease in lysophospholipids and omega-3 fatty acids with obesity metabolism. Ceramides, phosphatidylethanolamines and phosphatidylinositols were associated with insulin resistance and cardiometabolic risk, whereas sphingomyelins showed inverse associations. Additionally, a panel of three lipids predicted hepatic steatosis as effectively as liver enzymes. Lipids partially mediated the association between obesity and cardiometabolic traits. The nonpharmacological management reduced levels of ceramides, phospholipids and triglycerides, indicating that lowering the degree of obesity could partially restore a healthy lipid profile in children and adolescents., (© 2024. The Author(s).)

Background: Helicobacter pylori colonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gastrointestinal microbiota composition. Previous studies have explored a potential association between H. pylori infection and pediatric obesity with varying results. Considering the immunomodulatory effects of early-life infection with H. pylori that can confer beneficial effects, we hypothesized that we would find an inverse relationship between H. pylori seropositivity and obesity among Danish children and adolescents., Methods: We assessed H. pylori seroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, aged 6 to 19 years, and examined its association with obesity and other cardiometabolic risk factors., Results: No association was found between H. pylori and body mass index standard deviation score (BMI SDS). H. pylori seropositivity was, however, significantly associated with higher fasting plasma glucose levels and the prevalence of hyperglycemia., Conclusion: While we did not find an association between H. pylori seropositivity and BMI SDS, we observed a significant association with higher fasting plasma glucose levels and increased prevalence of hyperglycemia, suggesting that H. pylori infection may contribute to impaired glucose regulation in Danish children and adolescents., (© 2024. The Author(s).)

Background and Aim: Cerebral palsy (CP) is the most common childhood motor disability, and the Cerebral Palsy Follow-Up Program (CPUP) in Nordic countries uses a traffic light system for passive range of motion (ROM) assessment to aid interpretation and guide decisions regarding interventions. However, the arbitrary chosen ROM threshold values and their potential clinical impact are uncertain. We investigated whether lower extremity ROM values were positively associated with gross motor function and whether gross motor function scores differ between the CPUP ROM thresholds., Methods: This was a cross-sectional analysis of CPUP data for 841 ambulatory children and adolescents with CP, at a mean (SD) age of 9 (3). Regression analyses were employed to explore the relationship between gross motor capacity and performance (using the Gross Motor Function Measure (GMFM-66) and the Functional Mobility Scale (FMS) 5/50/500 m, respectively) and lower extremity ROM, measured with a goniometer. ROM was assessed both as continuous and categorical variables., Results: We found that two out of ten continuous ROM measures were positively associated with gross motor function. Limited differences in gross motor function between the ROM thresholds were seen for seven out of ten ROM measures. The CPUP traffic light thresholds primarily differentiated gross motor function between the red and green categories, predominantly for the subgroup of participants with bilateral spastic CP., Conclusion: Limited associations between passive ROM and gross motor function in children and adolescents with CP were observed, indicating that there is more to consider than ROM when identifying whether interventions are needed., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations., Methods: We used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels., Findings: BW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (βadj [95% CI per SD] for obesity: -0.12 [-0.15, -0.08]; normal weight: -0.04 [-0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: -0.11 [-0.14, -0.08]; normal weight: -0.02 [-0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: -0.12 [-0.16, -0.08]; normal weight: -0.06 [-0.11, -0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05)., Interpretation: We identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD., Funding: Novo Nordisk Foundation (NNF15OC0016544, NNF0064142 to T.H., NNF15OC0016692 to T.H. and A.K., NNF18CC0033668 to S.E.S, NNF18SA0034956 to C.E.F., NNF20SA0067242 to DCA, NNF18CC0034900 to NNF CBMR), The Innovation Fund Denmark (0603-00484B to T.H.), The Danish Cardiovascular Academy (DCA) and the Danish Heart Foundation (HF) (PhD2021007-DCA to P.K.R, 18-R125-A8447-22088 (HF) and 21-R149-A10071-22193 (HF) to M.A.V.L., PhD2023009-HF to L.A.H), EU Horizon (668031, 847989, 825694, 964590 to A.K.), Innovative Health Initiative (101132901 for A.K.), A.P. Møller Foundation (19-L-0366 to T.H.), The Danish National Research Foundation, Steno Diabetes Center Sjælland, and The Region Zealand and Southern Denmark Health Scientific Research Foundation., Competing Interests: Declaration of interests C.E.F. has received speaker honoria from The Danish Society for General Practice, Novo Nordisk, Nestlé and payment for manuscript writing from The Danish Health Authority. C.B. and T.H. have stocks in Novo Nordisk. A.K. receives royalties from Gyldendal, payment for lectures from Norgine, Siemens, Nordic Bioscience, Novo Nordisk. A.K. has two patents planned/pending, participates on an advisory board for Norgine, Siemens, Novo Nordisk, B&I. A.K. has a leadership role as the Secretary General European Association for the Study of The Liver (EASL) 2023–2025. A.K. has received equipment, materials, and drugs from Norgine (Rifaximin), Siemens (ELF Test), Echosence (FibroScan), and Nordic Bioscience (ECM markers). A.K. has finical interest as the Board member and co-founder Evido. J-C.H. has received payment for expert testimony from Novo Nordisk and support for meetings and travel from Rhytm, provides training and treatment of obesity. We declare no other competing interests from remaining coauthors., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Context: Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion., Objective: To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW)., Methods: 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated., Results: Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI., Conclusion: Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Aim: To describe the recreational screen time behaviour of 8-16-year-olds diagnosed with cerebral palsy (CP) and explore associations between health-related quality of life, sleep duration and physical activity behaviour versus screen time., Methods: This cross-sectional study used proxy-reported questionnaire data of 381 ambulatory (with or without assistance) 8-16-year-olds diagnosed with CP corresponding to Gross Motor Function Classification System (GMFCS) levels I-III. Descriptive statistics were used to report age, sex and the GMFCS level. The potential associations of health-related quality of life, physical activity behaviour and sleep duration (dependent variables) versus screen time (independent variable) were determined using multiple linear regression. Health-related quality of life was evaluated using the Pediatric Quality of Life Inventory, including seven dimensions: Daily Activities; School Activities; Movement and Balance; Pain and Hurt; Fatigue; Eating Activities; and Speech and Communication., Results: The participants spent a median screen time of 3.9 h daily. The boys spent a longer screen time during weekends than the girls (p = 0.003). Boys spent more time on games (p < 0.001), whereas girls spent more time on social media and video calls (p < 0.001). Increasing age (p < 0.001) was associated with increased screen time but did not differ between the GMFCS levels. Sleep duration, perceived fatigue and perceived movement and balance correlated negatively with screen time., Conclusion: This study sheds light on the recreational screen time habits of ambulatory children and adolescents diagnosed with CP. Further investigation into the observed associations is warranted to investigate potential causation and relationships between sleep behaviour, quality of life and screen time behaviour., (© 2024 John Wiley & Sons Ltd.)

Bilirubin is the end product of heme catabolism, mainly produced by the breakdown of mature red blood cells. Due to its anti-inflammatory, antioxidant, antidiabetic, and antilipemic properties, circulating bilirubin concentrations are inversely associated with the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality in adults. Some genetic loci associated with circulating bilirubin concentrations have been identified by genome-wide association studies in adults. We aimed to examine the relationship between circulating bilirubin, cardiometabolic risk factors, and inflammation in children and adolescents and the genetic architecture of plasma bilirubin concentrations. We measured fasting plasma bilirubin, cardiometabolic risk factors, and inflammatory markers in a sample of Danish children and adolescents with overweight or obesity ( n = 1530) and in a population-based sample ( n = 1820) of Danish children and adolescents. Linear and logistic regression analyses were performed to analyze the associations between bilirubin, cardiometabolic risk factors, and inflammatory markers. A genome-wide association study (GWAS) of fasting plasma concentrations of bilirubin was performed in children and adolescents with overweight or obesity and in a population-based sample. Bilirubin is associated inversely and significantly with a number of cardiometabolic risk factors, including body mass index (BMI) standard deviation scores (SDS), waist circumference, high-sensitivity C-reactive protein (hs-CRP), homeostatic model assessment for insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), triglycerides, and the majority of measured inflammatory markers. In contrast, bilirubin was positively associated with fasting plasma concentrations of alanine transaminase (ALT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SDS), and the inflammatory markers GH, PTX3, THBS2, TNFRSF9, PGF, PAPPA, GT, CCL23, CX3CL1, SCF, and TRANCE. The GWAS showed that two loci were positively associated with plasma bilirubin concentrations at a p -value threshold of <5 × 10 -8 (rs76999922: β = -0.65 SD; p = 4.3 × 10 -8 , and rs887829: β = 0.78 SD; p = 2.9 × 10 -247 ). Approximately 25% of the variance in plasma bilirubin concentration was explained by rs887829. The rs887829 was not significantly associated with any of the mentioned cardiometabolic risk factors except for hs-CRP. Our findings suggest that plasma concentrations of bilirubin non-causally associates with cardiometabolic risk factors in children and adolescents.

Background & Aims: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents., Approach & Results: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1 H-MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1-SD unit: 2.17, p = 9.7E-10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76-0.81). Combining the GRS with clinical measures (waist-to-height ratio [WHtR] SDS, ALT, and HOMA-IR) increased the AUC up to 0.86 (95% CI 0.84-0.88)., Conclusions: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Children and adolescents with cerebral palsy (CP) show a reduced physical activity (PA) level compared with their typically developed peers. This study aimed to identify potential predictors of objectively evaluated habitual PA using data from a national clinical registry-the Cerebral Palsy Follow-Up Program (CPFP)-and proxy-reported questionnaires. Data from the CPFP database showed that female sex was associated with a lower PA level. Additional questionnaire data revealed age, popliteal angle limitation, Pediatric Outcomes Data Collection Instrument-Sports and Physical Functioning Scale score, screen time, Functional Mobility Scale score at 50 m, and fatigue as predictors. The proposed models can be used for the prediction and early detection of the PA level and consequently for the potential improvement among ambulant/semiambulant individuals with CP. Further research should investigate the predictive impact of personal, social, and environmental factors on the PA level and the gap in PA levels between girls and boys.

Background Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 is a scavenger receptor for oxidized low-density lipoprotein. In adults, higher soluble lectin-like ox-LDL receptor-1 (sLOX-1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweight/obesity remains uncertain. Methods and Results Analyses were based on the cross-sectional HOLBAEK Study, including 4- to 19-year-olds from an obesity clinic group with body mass index >90th percentile (n=1815) and from a population-based group (n=2039). Fasting plasma levels of sLOX-1 and inflammatory markers were quantified, cardiometabolic risk profiles were assessed, and linear and logistic regression analyses were performed. Pubertal/postpubertal children and adolescents from the obesity clinic group exhibited higher sLOX-1 levels compared with the population ( P <0.001). sLOX-1 positively associated with proinflammatory cytokines, matrix metalloproteinases, body mass index SD score, waist SD score, body fat %, plasma alanine aminotransferase, serum high-sensitivity C-reactive protein, plasma low-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure SD score, and inversely associated with plasma high-density lipoprotein cholesterol (all P <0.05). sLOX-1 positively associated with high alanine aminotransferase (odds ratio [OR], 1.16, P =4.1 E-04), insulin resistance (OR, 1.16, P =8.6 E-04), dyslipidemia (OR, 1.25, P =1.8 E-07), and hypertension (OR, 1.12, P =0.02). Conclusions sLOX-1 levels were elevated during and after puberty in children and adolescents with overweight/obesity compared with population-based peers and associated with inflammatory markers and worsened cardiometabolic risk profiles. sLOX-1 may serve as an early marker of cardiometabolic risk and inflammation in pediatric overweight/obesity. Registration The HOLBAEK Study, formerly known as The Danish Childhood Obesity Biobank, ClinicalTrials.gov identifier number NCT00928473, https://clinicaltrials.gov/ct2/show/NCT00928473 (registered June 2009).

Background: Diagnosis of nonalcoholic fatty liver disease in children and adolescents currently requires advanced or invasive technologies., Objectives: We aimed to develop a method to improve diagnosis, using body composition indices and liver biochemical markers., Methods: To diagnose non-alcoholic fatty liver disease, 767 Danish children and adolescents underwent clinical examination, blood sampling, whole-body dual-energy X-ray absorptiometry scanning and proton magnetic resonance spectroscopy for liver fat quantification. Fourteen variables were selected as a starting point to construct models, narrowed by stepwise selection. Individuals were split into a training set for model construction and a validation test set. The final models were applied to 2120 Danish children and adolescents to estimate the prevalence., Results: The final models included five variables in different combinations: body mass index-standard deviation score, android-to-gynoid-fat ratio, android-regional fat percent, trunk-regional fat percent and alanine transaminase. When validated, the sensitivity and specificity ranged from 38.6% to 51.7% and 87.6% to 91.9%, respectively. The estimated prevalence was 24.2%-35.3%. Models including alanine transaminase alongside body composition measurements displayed higher sensitivity., Conclusions: Body composition indices and alanine transaminase can be used to estimate non-alcoholic fatty liver disease, with 38.6%-51.7% sensitivity and 87.6%-91.9%, specificity, in children and adolescents with overweight (including obesity). These estimated a 24.2%-35.3% prevalence in 2120 patients., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Context: In adults, hyperglucagonemia is associated with type 2 diabetes, impaired glucose tolerance, and obesity. The role of glucagon in pediatric overweight/obesity remains unclear., Objective: We examined whether fasting concentrations of glucagon are elevated in youth with overweight/obesity and whether this associates with cardiometabolic risk profiles., Methods: Analyses were based on the cross-sectional HOLBAEK study, including children and adolescents 6 to 19 years of age, with overweight/obesity from an obesity clinic group (n = 2154) and with normal weight from a population-based group (n = 1858). Fasting concentrations of plasma glucagon and cardiometabolic risk outcomes were assessed, and multiple linear and logistic regressions models were performed., Results: The obesity clinic group had higher glucagon concentrations than the population-based group (P < 0.001). Glucagon positively associated with body mass index (BMI) standard deviation score (SDS), waist, body fat %, liver fat %, alanine transaminase (ALT), high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance, insulin, C-peptide, LDL-C, triglycerides, SDS of diastolic and systolic blood pressure, and was inversely associated with fasting glucose. The inverse relationship between glucagon and glucose was attenuated in individuals with high BMI SDS and high fasting insulin. Glucagon was associated with a higher prevalence of insulin resistance, increased ALT, dyslipidemia, and hypertension, but not with hyperglycemia. Glucagon was positively associated with fasting total glucagon-like peptide-1., Conclusion: Compared with normal weight peers, children and adolescents with overweight/obesity had elevated concentrations of fasting glucagon, which corresponded to worsened cardiometabolic risk outcomes, except for hyperglycemia. This suggests hyperglucagonemia in youth may precede impairments in glucose regulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Overweight in early childhood often tracks into adolescence and adulthood and early childhood is a critical period for developing sustained overweight. This study aims to investigate the early detection of childhood overweight (including obesity) and related cardiometabolic complications in a Danish population-based cohort of children aged 2.5-8 years in collaboration with primary care municipal dental clinics and public health nurses., Methods: In this prospective population-based cohort study, 335 pre-school children (age 2.5 and 5 years) were recruited from municipal dental clinics, and 657 school children (age 6-8 years) by public health nurses. A subgroup of 392 children (40%) participated in additional hospital-based examinations including blood pressure measurement and a blood sample. Children were re-examined approximately one year later., Results: The prevalence of overweight was 13.73% in pre-school children and 13.69% in school children at baseline. In the pre-school children, differences in cardiometabolic risk markers between children with and without overweight were minor, whereas in school children with overweight, cardiometabolic derangements were manifest including significantly higher levels of fasting glucose, insulin, homoeostasis model of assessment for insulin resistance, triglycerides, and alanine aminotransferase and lower levels of high-density lipoprotein cholesterol. During follow-up the prevalence of overweight did not change in pre-school children but increased to 17.0% in school children., Conclusions: Existing contacts with the primary health care sector, including dental care, can successfully be used for detection of overweight. This study suggests that early detection should be initiated at pre-school ages since overweight-related complications are already established by school ages., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the relationship between in utero growth conditions, as indicated by neonatal anthropometric measures, and childhood obesity treatment response, to examine the potential usefulness of neonatal anthropometrics as a potential childhood obesity treatment stratification tool., Study Design: The study included 2474 children and adolescents with obesity (mean age, 11.2 years; range, 5.0-18.9 years) treated at the Children's Obesity Clinic in Holbæk, Denmark. Treatment response was registered prospectively, and neonatal data were collected from national electronic registers., Results: Birth weight, birth length, birth weight for gestational age, and large for gestational age status were positively associated with the degree of obesity at treatment initiation. After a mean (SD) of 1.27 (0.69) years of enrollment in obesity treatment, the children exhibited a mean reduction of -0.32 (0.50) in body mass index SD score. No significant associations between neonatal anthropometric measures and childhood obesity treatment response were detected., Conclusions: Neonatal anthropometric measures were positively associated with the degree of obesity at treatment initiation but not with response to multidisciplinary treatment of childhood obesity. Individualization of obesity treatment based on neonatal anthropometry does not seem warranted., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Efficient obesity treatment protocols are lacking. This study reports treatment results from a web-based application, originally developed for use in an in-person healthcare setting providing health, overweight, and obesity management., Methods: The web application DrHolmApp (WADHA) was evaluated in adult users two years after it was launched. The WADHA provides a personal and tailored treatment plan comprising a series of detailed action advices on everyday life, constructed from the user's input to a thorough online questionnaire. Throughout the subscription period, the WADHA users have full access to online healthcare professional support. We conducted a longitudinal cohort study using self-reported data., Results: This study included 940 adult WADHA users (861 female). The median body mass index (BMI) change across all WADHA users was -0.63 BMI points (95% CI: -0.7 to -0.57, P<0.001). 665 (71%) of all WADHA users reduced their BMI (median reduction: 0.94, 95% CI: 0.88 to 1.02). In the subset with obesity (n=675), BMI was reduced in 72%. The median number of days per week with physical activity for at least one hour per day increased with 1.5 days per week (from 2 days per week at baseline, P<0.001). Subsequently, the WADHA users improved their mood, quality of life, and body image satisfaction and reduced their appetite, bullying, and wish for weight loss (all P<0.001). A higher number of consultations associated with greater weight loss (P<0.001) independent of age and degree of obesity at treatment initiation., Conclusions: Seventy-one percent of the WADHA users experienced weight loss, concomitant to an increased level of physical activity, improved mood, quality of life, and body image satisfaction, and reduced appetite, degree of bullying, and wish for weight loss., Keywords: Body mass index (BMI); mobile health (mHealth); obesity; treatment; weight loss., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/mhealth-21-8). CEF reports stock or stock options in Dr Holm group. JCH reports ownership of Dr Holm Group and serves as an advisor of The Novo Nordisk Global Childhood Obesity advisory board, Advisor and lecturer of Rhythm Pharmaceuticals, advisor and assessor of German Centre for Child and Youth Health, and Executive member of European Association for the Study of Obesity (EASO). AFP declares no conflict of interest, but JCH is his father-in-law. The other authors have no conflicts of interest to declare., (2022 mHealth. All rights reserved.)

Gut viruses are important, yet often neglected, players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies has been increasing; however, we are still only scratching the surface of the immense viral diversity. In this study, 254 virus-enriched fecal metagenomes from 204 Danish subjects were used to generate the D anish E nteric V ir o me C atalog (DEVoC) containing 12,986 nonredundant viral scaffolds, of which the majority was previously undescribed, encoding 190,029 viral genes. The DEVoC was used to compare 91 healthy DEVoC gut viromes from children, adolescents, and adults that were used to create the DEVoC. Gut viromes of healthy Danish subjects were dominated by phages. While most phage genomes (PGs) only occurred in a single subject, indicating large virome individuality, 39 PGs were present in more than 10 healthy subjects. Among these 39 PGs, the prevalences of three PGs were associated with age. To further study the prevalence of these 39 prevalent PGs, 1,880 gut virome data sets of 27 studies from across the world were screened, revealing several age-, geography-, and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide-a crAss-like phage (20.6% prevalence), belonging to the tentative AlphacrAssvirinae subfamily, and a previously undescribed circular temperate phage infecting Bacteroides dorei (14.4% prevalence), called LoVEphage because it encodes l ots o f v iral e lements. Due to the LoVEphage's high prevalence and novelty, public data sets in which the LoVEphage was detected were de novo assembled, resulting in an additional 18 circular LoVEphage-like genomes (67.9 to 72.4 kb). IMPORTANCE Through generation of the DEVoC, we added numerous previously uncharacterized viral genomes and genes to the ever-increasing worldwide pool of human gut viromes. The DEVoC, the largest human gut virome catalog generated from consistently processed fecal samples, facilitated the analysis of the 91 healthy Danish gut viromes. Characterizing the biggest cohort of healthy gut viromes from children, adolescents, and adults to date confirmed the previously established high interindividual variation in human gut viromes and demonstrated that the effect of age on the gut virome composition was limited to the prevalence of specific phage (groups). The identification of a previously undescribed prevalent phage illustrates the usefulness of developing virome catalogs, and we foresee that the DEVoC will benefit future analysis of the roles of gut viruses in human health and disease.

Introduction: Children and adolescents with cerebral palsy may be trapped in a vicious circle of low physical fitness, resulting in deconditioning that causes a further decrease in physical activity (PA), a lower quality of life and an increased risk of developing non-communicable diseases. Therefore, establishing a healthy and active lifestyle during childhood is even more important for individuals with a disability. However, the factors that influence habitual PA in children and adolescents with cerebral palsy remain unknown.The present protocol outlines a prospective cohort study with the aim of investigating potential predictors of habitual PA in children and adolescents with cerebral palsy in order to provide evidence for optimising PA levels and associated overall health., Methods and Analysis: This prospective cohort study will enrol participants with cerebral palsy between the ages of 8 and 15 years at Gross Motor Function Classification System levels I-III. Using a modified version of the International Classification of Functioning, Disability and Health model as a conceptual analytical framework, the analysis will be divided into six components and will provide predictors for habitual PA measured by accelerometry. The potential predictive variables are registry data on physical function (Danish Cerebral Palsy Follow-Up Programme); validated proxy-reported questionnaires on quality of life (Paediatric Quality of Life Inventory), overall health, pain and participation in daily activities (Paediatric Outcomes Data Collection Instrument) and supplementary questions regarding sleep, screen time and socioeconomic status., Ethics and Dissemination: The project is approved by the Danish Data Protection Agency (19/16396) and has been declared not notifiable by the Regional Committee on Health Research Ethics, cf. Committee Act Art. 14, paragraph 1 (S-20192000-23). The study results will be published in international peer-reviewed journals, presented at international conferences, and published in a PhD dissertation., Trial Registration Number: NCT04614207., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Human milk oligosaccharides (HMOs) impact the intestinal microbiota by increasing beneficial bacteria in infants and adults, and are safe and well tolerated in these age groups. Effects on intestinal microbiota, safety, and digestive tolerance in children have not been, however, assessed. The aims of this trial were to evaluate if HMOs are able to specifically modulate the intestinal microbiota in children, and to assess safety and digestive tolerance., Methods: In this randomized, double-blinded, placebo-controlled trial, 75 children with overweight (including obesity) ages 6 to 12 years were randomized to receive 2'-fucosyllactose (2'FL), a mix of 2'FL and lacto-N-neotetraose (Mix), or a glucose placebo orally administrated once per day for 8 weeks., Results: The relative abundance of bifidobacteria increased significantly after 4 (P < 0.001) and 8 (P = 0.025) weeks of intervention in the 2'FL-group and after 4 weeks (P = 0.033) in the Mix-group, whereas no change was observed in the placebo group. Compared with placebo, the 2'FL-group had a significant increase in bifidobacteria abundance after 4 weeks (P < 0.001) and 8 weeks (P = 0.010) and the Mix-group showed a tendency to increased bifidobacteria abundance after 4 (P = 0.071) and 8 weeks (P = 0.071). Bifidobacterium adolescentis drove the bifidogenic effect in the 2 groups. Biochemical markers indicated no safety concerns, and the products did not induce digestive tolerance issues as assessed by Gastrointestinal Symptoms Rating Scale and Bristol Stool Form Scale., Conclusions: Both 2'FL and the Mix beneficially modulate intestinal microbiota by increasing bifidobacteria. Furthermore, supplementation with either 2'FL alone or a Mix is safe and well tolerated in children., Competing Interests: L.K.V., I.D.A., and B.M. were employed at Glycom A/S, Denmark. The remaining authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

WHO declared obesity a disease in 1979 and has named childhood obesity one of the most pervasive health challenges in the 21st century. The Danish Paediatric Society concordantly declares childhood obesity a chronic disease. Early treatment of obesity can prevent the disease from escalating into significant psychosocial and somatic complications arising in most organs with the potential to compromise normal growth and development. As argued in this review, the recognition of childhood obesity as a disease will help to increase the development of new treatment measures and health policies to prevent and manage obesity.

Objectives: To determine the prevalence of Melanocortin-4 Receptor (MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers., Methods: Using target region capture sequencing, an MC4R mutation screen was performed in 1261 Danish children and adolescents enrolled at a tertiary multidisciplinary childhood obesity treatment center. Measurements of anthropometrics, blood pressure, fasting blood biochemistry including lipid and hormone levels, and dual-energy X-ray absorptiometry were performed at baseline and throughout treatment., Results: Of 1209 children and adolescents that met all criteria to be included in the described analyses, 30 (2.5%) carried damaging or unresolved MC4R mutations. At baseline, mutation carriers exhibited higher concentrations of plasma thyroid-stimulating hormone (p = 0.003), and lower concentrations of plasma thyroxine (p = 0.010) compared to noncarriers. After a median of 1 year of treatment (range 0.5-4.0 years), body mass index (BMI) standard deviation score (SDS) was reduced in noncarriers but not in carriers, and this difference in treatment response was statistically significant (p = 0.005). Furthermore, HDL cholesterol was reduced in carriers, a response significantly different from that of noncarriers (p = 0.017)., Conclusion: Among Danish children and adolescents with overweight or obesity entering a tertiary lifestyle intervention, 2.5% carried damaging or unresolved MC4R mutations. In contrast to noncarriers, carriers of damaging or unresolved MC4R mutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on the MC4R genotype.

Background: Children with cerebral palsy often exhibit an altered gait pattern; however, it is uncertain whether the use of an instrumented gait analysis in interdisciplinary interventions affects the perceived experience of family-centered service (FCS) and/or gross motor function. The aim of this study is to investigate whether individually tailored interdisciplinary interventions, based on an instrumented gait analysis report, has a superior effectiveness on perceived FCS and gross motor function in children with cerebral palsy, compared to 'care as usual' without the use of instrumented gait analysis. Furthermore, to investigate potential associations between perceived FCS and gross motor function improvement with the goal of improving future therapy on gross motor function., Method: This is a sequel analysis on tertiary outcome measures from a prospective, single blind, randomized, parallel group study including two groups of 30 children aged 5-8 years with spastic cerebral palsy at Gross Motor Function Classification System levels I-II (n = 60). The intervention group underwent a three-dimensional gait analysis, from which a clinical report was written with recommendations on interdisciplinary interventions, such as physical therapy, orthopedic surgery, orthotics or spasticity management. To assess effectiveness on perceived FCS and gross motor function, at baseline, 26 weeks and 52 weeks, the five domains in the Measure of Processes of Care (MPOC-20) (Enabling and partnership, Providing general information, Providing specific information about the child, Respectful and supportive service, and Coordinated and comprehensive care) and the Gross Motor Function Measurement (GMFM-66) were used as outcome measures., Results: No significant differences in between-group change scores in any of the five MPOC-20 domains were observed (p = 0.40-0.97). In favor of the intervention group a significantly higher between-group change score in GMFM-66 (mean difference: 3.05 [95%CI: 1.12-4.98], p = 0.003) after 52 weeks was observed., Conclusion: The addition of an instrumented gait analysis report to 'care as usual' did not improve the parents' perceptions of FCS in treatment of children with cerebral palsy. However, superior improvement in the GMFM-66 was observed in the intervention group, suggesting meaningful gross motor function improvement., Trial Registration: Clinical Trials, NCT02160457 . Registered June 10th 2014.

Background: Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear., Methods: We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants., Results: Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%)., Conclusions: Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019)., (Published by Oxford University Press on behalf of the Endocrine Society 2019.)

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurring disease mainly observed in adults. Obesity is considered an important independent factor in HS development and is associated with a higher prevalence of HS in children. We aimed to characterize the clinical presentation of HS in overweight and obese children and adolescents., Methods: We performed a cross-sectional observational study during January 2007-April 2015. Overweight and obese patients (5-17 years of age, BMI> 90th percentile) referred to The Children's Obesity Clinic, Department of Paediatrics, Copenhagen University Hospital Holbaek, Denmark, underwent screening for dermatological conditions. A dermatologist ascertained the diagnosis of HS, and disease severity was assessed using Hurley staging and Sartorius score. Tobacco smoke exposure, body mass index (BMI) standard deviation score (SDS), and psychiatric comorbidities were recorded. Our cohort was compared with a reference cohort recruited in a previous study., Results: A total of 195 children and adolescents underwent screening for dermatological conditions. Nine patients screened positive, and six of these patients were available for examination of whom five presented with HS. All HS cases were mild (median Sartorius score of 9). Four of the five patients (with varying constellations) reported tobacco exposure, a positive family history of HS, and exhibited psychiatric comorbidities., Conclusion: Our findings support that the presence of pediatric HS is correlated with familial disposition to HS and psychiatric comorbidities., (© 2019 The International Society of Dermatology.)

Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear., Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization., Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y., Results: WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal., Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity., (Copyright © American Society for Nutrition 2019.)

Background: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children., Methods: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years., Results: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHR adjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536)., Conclusions: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.

Background: Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood., Objective: This study aims to generate pediatric age and sex-specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C-peptide, and homeostasis model assessment: insulin resistance (HOMA-IR) in Danish/North-European white children and adolescents from a population-based cohort and to compare values from children and adolescents with overweight/obesity with this reference., Methods: The population- and obesity clinic-based cohorts consisted of 2451 and 1935 children and adolescents between 6 and 18 years of age. Anthropometric measurements and blood samples were obtained and percentile curves were calculated., Results: In the population-based cohort, glucose, insulin, and HOMA-IR values increased before the expected onset of puberty (P < .05). Thereafter, all variables decreased in girls (P < .05) and HbA1c decreased in boys (P < .05). Concentrations of all measured markers of glucose metabolism were higher in the obesity clinic-based cohort than the population-based cohort (both sexes P < .001). Specifically, insulin and HOMA-IR continued to increase to 18 years in the clinic-based cohort, particularly among boys., Conclusions: Fasting glucose, insulin, and HOMA-IR change during childhood, making pediatric reference values essential for timely identification of derangements in glucose metabolism. Children and adolescents with obesity exhibit increased concentrations of these biomarkers., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Thyroid-stimulating hormone (TSH) and thyroid hormones influence the functions of many organ systems, as well as child development and growth. Several studies have reported an association between ethnicity and thyroid hormones. This study aims to explore pediatric serum concentrations of TSH, free triiodothyronine (fT3), and free thyroxine (fT4) and their relation to age and sex and subsequently to present pediatric reference intervals from healthy Danish/North-European white children. A population-based cohort in Denmark of 2411 (1435 girls) healthy school children and adolescents aged 6.0-18.9 years were included. Fasting concentrations of serum TSH, fT3, and fT4 were determined from venous blood samples using immunologic chemiluminescent assays. Age- and sex-dependent percentiles were generated using the GAMLSS function. Median values of fT3 and fT4, but not TSH, were lower in the older age group compared with the youngest age group for both sexes (all p < .05). A significant difference for fT3 was found between the sexes for all age groups (all p < .001). fT4 was negatively correlated with body mass index standard deviation scores in boys. In conclusion, serum concentrations of thyroid hormones vary during childhood and adolescence and differ with age and sex.

Objective: To investigate whether children and adolescents exhibiting an impaired glucose metabolism are more obese at treatment entry and less likely to reduce their degree of obesity during treatment., Methods: The present study is a longitudinal observational study, including children and adolescents from the Children's Obesity Clinic, Holbaek, Denmark. Anthropometrics, pubertal development, socioeconomic status (SES), and fasting concentrations of plasma glucose, serum insulin, serum C-peptide, and whole blood glycosylated hemoglobin (HbA1c) were collected at treatment entry and at follow-up. Proxies of Homeostasis Model Assessment 2-insulin sensitivity (HOMA2-IS) and Homeostasis Model Assessment 2-β-cell function (HOMA2-B) were calculated with the Homeostasis Model Assessment 2 program., Results: In total, 569 (333 boys) patients, median 11.5 years of age (range 6-22 years), and median body mass index (BMI) z-score 2.94 (range 1.34-5.54) were included. The mean BMI z-score reduction was 0.31 (±0.46) after 13 months (range 6-18) of treatment. At treatment entry, patients with impaired estimates of glucose metabolism were more obese than normoglycemic patients. Baseline concentration of C-peptide was associated with a lower weight loss during treatment in girls (P = .02). Reduction in the insulin concentrations was associated with reduction in BMI z-score in both sexes (P < .0001, P = .0005). During treatment, values of glucose, HbA1c, HOMA2-IS, and HOMA2-B did not change or impact the treatment outcome, regardless of age, sex, SES, or degree of obesity at treatment entry., Conclusion: The capability to reduce weight during multidisciplinary treatment in children and adolescents with overweight/obesity is not influenced by an impaired glucose metabolism at study entry or during the course of treatment., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Whether the definitions of impaired fasting glucose (IFG) from the American Diabetes Association (ADA) and the World Health Organization (WHO) differentially impact estimates of the metabolic profile and IFG-related comorbidities in Danish children and adolescents is unknown., Methods: Two thousand one hundred and fifty four (979 boys) children and adolescents with overweight or obesity (median age 12 years) and 1824 (728 boys) children with normal weight (median age 12 years) from The Danish Childhood Obesity Biobank were studied. Anthropometrics, blood pressure, puberty, and fasting concentrations of glucose, insulin, glycosylated hemoglobin (HbA1c), and lipids were measured., Results: About 14.1% of participants with overweight or obesity exhibited IFG according to the ADA and 3.5% according to the WHO definition. Among individuals with normal weight, the corresponding prevalences were 4.3% and 0.3%. IFG was associated with a higher systolic blood pressure, higher concentrations of HbA1c, insulin, C-peptide (P < .0001) and triglycerides (P = .03), and lower HOMA2-IS and HOMA2-B (P < .0001) independent of sex, age, puberty, waist-to-height ratio, and degree of obesity. Furthermore, IFG was associated with a higher risk for hypertension (OR = 1.66 [95%CI: 1.21; 2.28], P = .002) and dyslipidemia (OR = 1.90 [95%CI: 1.38; 2.56], P < .0001) compared with the group without IFG independent of age, sex, and puberty., Conclusions: The prevalence of IFG, when applying the ADA criterion compared with the WHO criterion, was 4 times higher in individuals with overweight and obesity and 14 times higher in individuals with normal weight in this study sample of children and adolescents. IFG was associated with a higher risk of hypertension and dyslipidemia compared with their normoglycemic peers regardless of the definition applied., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The body mass index (BMI) standard deviation score (SDS) may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment., Methods: 876 children and adolescents (498 girls) with overweight/obesity, median age 11.2 years (range 1.6-21.7), and median BMI SDS 2.8 (range 1.3-5.7) were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4-7.4). Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469 individuals (264 girls). Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations., Results: At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10-4) and positively with TG (p = 9.7*10-6). Reductions in BMI SDS were associated with reductions in total body fat percentage (p<2*10-16) and percent truncal body fat (p<2*10-16). Furthermore, reductions in BMI SDS were associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL-ratio, and TG (all p <0.0001). Changes in body fat percentage seemed to mediate the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with available lipid concentrations, who increased their BMI SDS, 61% improved their body composition, and 80% improved their lipid concentrations., Conclusion: Reductions in the degree of obesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma lipid concentrations. Even in individuals increasing their BMI SDS, body composition and lipid concentrations may improve.

Background: Sufficient serum concentrations of vitamin D are required to maintain bone health during growth. The aims of this study were to determine whether vitamin D deficiency is more prevalent among children and adolescents with obesity compared to their normal weight peers and to identify clinical and biochemical variables associated with vitamin D deficiency., Methods: One thousand four hundred and eighty-four children and adolescents with overweight/obesity and 2143 population-based controls were recruited from the Danish Childhood Obesity Biobank. Anthropometric variables and fasting concentrations of serum 25-hydroxy vitamin D (25-OH-D), plasma parathyroid hormone (PTH), calcium and phosphate were assessed at baseline. Vitamin D deficiency was defined as serum 25-OH-D concentrations <30 nmol/L. Linear and logistic regressions were used to identify variables associated with vitamin D deficiency., Results: A total of 16.5% of the children and adolescents with obesity (body mass index [BMI] standard deviation score [SDS]>2.33) exhibited vitamin D deficiency, with an odds ratio (OR) 3.41 (confidence interval [CI]: 2.27-5.71; p<0.0001) for being vitamin D deficient compared to their normal weight peers. BMI-SDS was independently and inversely associated with serum 25-OH-D concentrations. Other independent risk factors for vitamin D deficiency were being older than 14 years (OR: 2.39; CI: 1.28-4.48; p=0.006), more than 4 daily hours of screen time (OR: 4.56; CI: 2.59-8.05; p<0.0001) and blood sample assessment during winter-spring (OR: 6.44; CI: 4.47-9.26; p<0.0001)., Conclusions: Vitamin D deficiency was common among Danish children and adolescents with obesity. The degree of obesity was independently associated with lower serum 25-OH-D concentrations.

Purpose: To investigate the effects of a multidisciplinary childhood obesity treatment programme on subjective evaluations of psychosocial well-being and quality of life., Methods: This longitudinal observational study included 1291 children, adolescents and young adults, 6-22 years of age, with overweight or obesity. At entry and after 2-82 months of obesity treatment, the patients evaluated the following domains of psychosocial well-being on a visual analogue scale: quality of life, mood, appetite, bullying, motivation for weight loss and body image satisfaction. The degree of overweight was calculated using a body mass index (BMI) standard deviation score (SDS) at each visit., Results: At entry, the mean BMI SDS was 2.81 (range: 1.35-6.65, 95% confidence interval (95% CI): 2.44-3.18). After a median of 14 months of treatment, the median reduction in BMI SDS was 0.29 (95% CI: 0.26-0.31, p < 0.0001). Improvements were observed in the domains of quality of life, mood, appetite, bullying and body image satisfaction (p < 0.0001). Larger reductions in BMI SDS were associated with greater improvements in the domains of quality of life (p = 0.001), mood (p = 0.04) and body image satisfaction (p < 0.0001), independent of BMI SDS at entry. However, improvements in psychosocial well-being were also observed in those increasing their BMI SDS (n = 315)., Conclusions: In a large group of children and youths, psychosocial well-being improved during a multidisciplinary childhood obesity treatment programme, irrespective of the degree of obesity at treatment entry. Greater reductions in BMI SDS were associated with greater improvements in psychosocial well-being, but even in the group increasing their BMI SDS improvements were observed.

Due to the pandemic of childhood obesity and thus obesity-related hypertension, improvements in treatment availability are needed. Hence, we investigated whether reductions in blood pressure (BP) would occur in children with overweight and obesity exhibiting prehypertension/hypertension during a community-based overweight and obesity treatment program, and if changes in body mass index (BMI) are associated with changes in BP. The study included 663 children aged 3-18 years with a BMI ⩾85th percentile for sex and age that entered treatment from June 2012 to January 2015. Height, weight and BP were measured upon entry and every 3-6 months. BMI and BP s.d. scores (SDSs) were calculated according to sex and age, or sex, age and height. Prehypertension was defined as a BP SDS ⩾1.28 and <1.65. Hypertension was defined as a BP SDS ⩾1.65. Upon entry, 52% exhibited prehypertension (11.9%) or exhibited hypertension (40.1%). After 12 months (range: 3-29) of treatment, 29.3% of the children with prehypertension/hypertension were normotensive. Children with systolic prehypertension/hypertension upon entry reduced their systolic BP SDSs by 0.31 (95% confidence interval (CI): 0.70-0.83, P<0.0001). Children with diastolic prehypertension/hypertension upon entry reduced their diastolic BP SDSs by 0.78 (95% CI: 0.78-0.86, P<0.0001). BMI SDS changes were positively associated with BP SDS changes (P<0.0001). Nonetheless, some children reduced BP SDSs while increasing their BMI SDSs, and prehypertension/hypertension developed in 23.3% of the normotensive children despite reductions in BMI SDSs (P<0.0001). These results suggest that community-based overweight and obesity treatment can reduce BP, and thus may help improve treatment availability.

Rationale and Objectives: The purpose of the present study was to obtain a cutoff value of liver fat content for the diagnosis of hepatic steatosis by comparing magnetic resonance (MR) spectroscopy results in children and adolescents with normal and excess weight., Materials and Methods: The study included 420 children and adolescents (91 normal-weight, 99 overweight, and 230 obese) 8-18 years of age. Proton magnetic resonance spectroscopy was performed with a 3T MR system using point resolved spectroscopy sequence with series echo times., Results: The mean absolute mass concentration of liver fat was obtained: 0.5 ± 0.04% in normal-weight boys; 0.5 ± 0.03% in normal-weight girls; 0.9 ± 0.16% in boys with overweight; 1.1 ± 0.24% in girls with overweight; 1.7 ± 0.24% in boys with obesity; and 1.4 ± 0.21% in girls with obesity. The cutoff value of absolute mass concentration of liver fat for hepatic steatosis was found to be 1.5%. Based on this cutoff value, hepatic steatosis was diagnosed in 16% of boys with overweight, 11% of girls with overweight, 32% of boys with obesity, and 27% of girls with obesity., Conclusions: Proton magnetic resonance spectroscopy was successfully applied to obtain the cutoff value of absolute mass concentration of liver fat for the diagnosis of hepatic steatosis in children and adolescents. Children and adolescents with obesity have higher risk of hepatic steatosis than their peers with overweight., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

We investigated the relationship between interview-based subjective ratings of physical activity (PA) engagement and accelerometer-assessed objectively measured PA in children and adolescents with overweight or obesity. A total of 92 children and adolescents (40 males, 52 females) with BMI ≥ 90th percentile for sex and age, aged 5-17 years had valid GT3X + accelerometer-assessed PA and interview-assessed self-reported information on PA engagement at the time of enrollment in a multidisciplinary outpatient tertiary treatment for childhood obesity. Accelerometer-derived mean overall PA and time spent in moderate to vigorous physical intensity were generated, applying cut-offs based on Vector Magnitude settings as defined by Romanzini et al. (2014), and a physical activity score (PAS) based on self-reported data. Overall, a higher self-reported PAS was correlated with higher accelerometer-assessed daily total PA levels ( r = 0.34, p < .01) and children who reported a high PAS were more physically active compared with children who reported a low PAS. There was a fair level of agreement between self-reported PAS and accelerometer-assessed PA (Kappa agreement = 0.23; 95% CI = [0.03, 0.43]; p = .01). PAS, derived from self-report, may be a useful instrument for evaluating PA at a group level among children and adolescents enrolled in multidisciplinary obesity treatment.

Background: Resistin is a hormone, mainly produced in macrophages and monocytes, believed to play an important role in the inflammatory response. It has been linked to several chronic diseases such as heart failure, inflammatory bowel disease, and insulin resistance. Pediatric reference levels are needed for the risk stratification and interpretation of individual serum resistin concentrations., Methods: A total of 1191 healthy, non-obese Danish schoolchildren (727 girls) aged 6-18years (median 11.9) were included. Fasting serum resistin concentrations were quantitated by Human Resistin ELISA Development kit, Duo Set (R&D Systems) following optimization., Results: The overall median resistin concentration was 8.93ng/mL (interquartile range (IQR): 6.19-13.33, range 1.57-35.84) in boys and 10.42ng/mL (IQR: 7.25-15.68, range 1.60-44.00) in girls. The resistin concentration correlated to relative BMI in both boys (p=0.02) and girls (p<0.0001). Percentiles for each age group were calculated alongside smoothed percentile curves and an age correlated increase was demonstrated, albeit only in girls (p=0.02) and not in boys (p=0.35)., Conclusion: Fasting serum resistin concentrations differ between sexes in healthy children and adolescents and are correlated both with the sex- and age adjusted BMI, and in girls to age., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Dyslipidemia is reported in 27 - 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity., Methods: A population-based cohort of 2141 (1275 girls) children and adolescents aged 6 - 19 (median 11.5) years was recruited from 11 municipalities in Denmark. Additionally, a cohort of children and adolescents of 1421 (774 girls) with overweight/obesity aged 6 - 19 years (median 11.8) was recruited for the study. Height, weight, and fasting plasma lipid concentrations were measured on all participants. Smoothed reference curves and percentiles were generated using the Generalized Additive Models for Location Scale and Shape package in the statistical software R., Results: In the population-based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low-density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with age in both sexes. In boys, non-HDL was lower in the oldest compared to the youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity in both sexes and for all ages except for TC in the youngest girls. The overall prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in the cohort with overweight/obesity compared with the population-based cohort was 6.2 (95% CI: 4.9 - 8.1, P < 2*10 -16 )., Conclusion: Fasting plasma lipid concentrations change during childhood and adolescence and differ with sex and age. Children and adolescents with obesity have increased concentrations of circulating lipids and exhibit an increased prevalence of dyslipidemia., Trial Registration: The study is part of The Danish Childhood Obesity Biobank; ClinicalTrials.gov ID-no.: NCT00928473 retrospectively registered on June 25th 2009.

Background: Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively., Objective: This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity., Methods: Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2-22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses., Results: No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10-16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10-20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 ∙ 10-11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10-10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p<0.0002). None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity., Conclusion: In a group of Danish children and adolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children.

Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread of microbes contributes to the development of metabolic traits. This is of major importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.

Objective: Thyroid abnormalities are common in obese children. The aim of the present study was to examine the prevalence of subclinical hypothyroidism (SH) and to determine how circulating thyroid hormone concentrations correlate with anthropometrics in Danish lean and obese children and adolescents., Methods: In this cross-sectional study, we included 3006 children and adolescents, aged 6-18 years, from the Registry of the Danish Childhood Obesity Biobank. The overweight/obese group (n=1796) consisted of study participants with a body mass index (BMI) standard deviation score (SDS) ≥1.28. The control group (n=1210) comprised lean children with a BMI SDS <1.28. All participants were characterized by anthropometrics (weight, height, and waist circumference) and fasting serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine (fT4) at baseline., Results: The prevalence of SH was higher among overweight/obese compared to lean study participants (10.4% vs. 6.4%, p=0.0001). In the overweight/obese group, fasting serum TSH concentrations were associated positively with BMI SDS (p<0.0001) and waist-height ratio (WHtR) (p<0.0001) independent of age, sex, and pubertal developmental stage, whereas fasting serum fT4 concentrations were associated positively only with WHtR. The odds ratio of exhibiting SH was 1.8 when being overweight/obese compared with lean (p=0.0007) and 1.8 when presenting with a WHtR >0.5 (p=0.0003)., Conclusion: The prevalence of SH was higher among overweight/obese study participants. The positive correlations of circulating TSH and fT4 with WHtR suggest that central obesity, independent of the overall degree of obesity, augments the risk of concurrent thyroid abnormalities in children and adolescents with obesity.

Background: Increased consumption of sweetened beverages has previously been linked to the degree of childhood obesity., Objective: The aim of the present study was to assess whether the intake of sweetened beverages, candy, snacks or fast food at baseline in a multidisciplinary childhood obesity treatment program was associated with the baseline degree of obesity or the treatment effect., Methods: This prospective study included 1349 overweight and obese children (body mass index standard deviation scores (BMI SDS) ≥ 1.64) enrolled in treatment at The Children's Obesity Clinic, Copenhagen University Hospital Holbaek. The children were evaluated at baseline and after up to 5.9 years of treatment (median 1.3 years)., Results: Both boys and girls decreased their BMI SDS during treatment with a mean decrease in boys of 0.35 (p < 0.0001) and in girls of 0.22 (p < 0.0001) after 1 year of treatment. There were no associations between the baseline intake of sweetened beverages, candy, snacks, and/or fast food and BMI SDS at baseline or the change in BMI SDS during treatment., Conclusions: The intake of sweetened beverages, candy, snacks or fast food when entering a childhood obesity treatment program was not associated with the degree of obesity at baseline or the degree of weight loss during treatment., (© 2016 World Obesity Federation.)

Background: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between MetS and ectopic fat may offer clinical relevance., Objectives: To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these., Methods: Two-hundred-and-sixteen children and adolescents (95 boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy., Results: We observed an odds ratio in girls with overweight/obesity of 12.2 (95% confidence interval: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence of muscular steatosis was 3.5 [1.4; 9.5] in girls with overweight/obesity and 1.0 [0.2; 5.6] in boys with overweight/obesity. Similar results were seen for girls with overweight/obesity exhibiting concurrent hepatic and muscular steatoses., Conclusion: Hepatic and muscular steatoses were associated with MetS among girls, but not among boys with overweight/obesity.

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10 -8 ). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (R g  = -0.22, P = 5.5 × 10 -13 ), T2D (R g  = -0.27, P = 1.1 × 10 -6 ) and coronary artery disease (R g  = -0.30, P = 6.5 × 10 -9 ). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10 -4 ). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated., Competing Interests: One of the authors discloses competing financial interests: Krina Zondervan has a scientific collaboration with Bayer HealthCare Ltd. and Population Diagnostics Inc.

Objective: The aim of this study was to investigate the prevalence of overweight/obesity among parents of children entering childhood obesity treatment and to evaluate changes in the parents' weight statuses during their child's treatment., Methods: The study included parents of 1,125 children and adolescents aged 3-22 years, who were enrolled in a multidisciplinary childhood obesity treatment program. At baseline, weight and height of the parents were obtained by self-reported information and parental body mass index (BMI) was calculated. Weight and height of the children were measured in the clinic and BMI standard deviation scores were calculated. Furthermore, anthropometric data from parents of 664 children were obtained by telephone interview after a mean of 2.5 years of treatment (ranging 16 days to 7 years), and changes in parental BMI were analyzed., Results: Data on changes in BMI were available in 606 mothers and 479 fathers. At baseline, the median BMI of the mothers was 28.1 kg/m2 (range: 16.9-66.6), and the median BMI of the fathers was 28.9 kg/m2 (range: 17.2-48.1). Seventy percent of the mothers and 80% of the fathers were overweight or obese at the time of their child's treatment initiation. Both the mothers and fathers lost weight during their child's treatment with a mean decrease in BMI in the mothers of 0.5 (95% CI: 0.2-0.8, p = 0.0006) and in the fathers of 0.4 (95% CI: 0.2-0.6, p = 0.0007). Of the overweight/obese parents, 60% of the mothers and 58% of the fathers lost weight during their child's treatment., Conclusion: There is a high prevalence of overweight/obesity among parents of children entering childhood obesity treatment. Family-based childhood obesity treatment with a focus on the child has a positive effect on parental BMI with both mothers and fathers losing weight., Trial Registration: ClinicalTrials.gov NCT00928473., Competing Interests: The authors have declared that no competing interests exist.

Background: Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity., Methods: We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism., Results: The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified., Conclusions: Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

Urinary excretion of the RNA and DNA oxidation markers, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in newly diagnosed adult type 2 diabetics are reported to be long-term predictors of mortality independent of conventional risk factors. In the current study, we investigated the relationships between urinary markers of nucleic acid oxidation concentrations and the degree of obesity and glucose metabolism in overweight compared to lean children. Forty-two (24 girls) overweight and 35 lean (19 girls) children and adolescents were recruited from the Registry of the Danish Childhood Obesity Biobank. Anthropometric measurements were collected at baseline and glucose metabolism was assessed by an oral glucose tolerance test. A urine sample was obtained during the test. Linear regression did not demonstrate any associations between the urinary markers and the degree of obesity or glucose metabolism in lean and obese children. However, sub-analyses adjusted for age, sex, and the degree of obesity showed positive associations between the 2 h glucose and the urinary markers, 8-oxoGuo (p = 0.02, r(2)= 0.63) and 8-oxodG (p = 0.046, r(2)= 0.48), and between the insulinogenic index and 8-oxoGuo (p = 0.03, r(2 )=( )0.60) in the 12 obese children exhibiting impaired glucose tolerance. Excretion of the urinary markers of nucleic acid oxidation and the degree of obesity or the glucose metabolism were not associated in this study. Nevertheless, obese children with impaired glucose tolerance seem to exhibiting an increased oxidative stress level, but due to the small sample size in this study, further investigations are required to elucidate this correlation.

Background: Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function., Methods: This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations., Results: The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage., Conclusions: A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss., Trial Registration: ClinicalTrials.gov registration number: NCT00928473 , the Danish Childhood Obesity Biobank. Registered June 25, 2009.

Background: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts., Methods: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model., Results: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026)., Conclusions: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.