[Obesity in children and adolescents is a chronic disease].

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.

Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations.

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.

Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations.

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.

Obesity is associated with vitamin D deficiency in Danish children and adolescents.

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.

Subjective evaluation of psychosocial well-being in children and youths with overweight or obesity: the impact of multidisciplinary obesity treatment.

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.

Dyslipidemia and reference values for fasting plasma lipid concentrations in Danish/North-European White children and adolescents.

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.

Reference values for fasting serum resistin in healthy children and adolescents.

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.

A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents.

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: ß = 0.112SD, p = 4.8 ∙ 10-16), FOXE1 (rs7847663: ß = 0.223SD, p = 1.5 ∙ 10-20), NR3C2 (rs9968300: ß = 0.194SD), p = 2.4 ∙ 10-11), VEGFA (rs2396083: ß = 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.

A hospital-based child and adolescent overweight and obesity treatment protocol transferred into a community healthcare setting.

BACKGROUND: Due to the pandemic of child and adolescent overweight and obesity, improvements in overweight and obesity treatment availability and accessibility are needed. METHODS: In this prospective study, we investigated if reductions in body mass index (BMI) standard deviation scores (SDS) and waist circumference (WC) would occur during 1.5 years of community-based overweight and obesity treatment based upon an effective hospital-based overweight and obesity treatment protocol, The Children's Obesity Clinics' Treatment protocol. Height, weight, and WC were measured at all consultations. Changes in BMI SDS and WC were analyzed using linear mixed models based upon the repeated measures in each child. RESULTS: From June 2012 to January 2015, 1,001 children (455 boys) were consecutively enrolled in the community-based treatment program. Upon entry, the median age was 11 years (range: 3-18), and the median BMI SDS was 2.85 (range: 1.26-8.96) in boys and 2.48 (range: 1.08-4.41) in girls. After 1.5 years of treatment BMI SDS was reduced in 74% of the children. BMI SDS was reduced by a mean of 0.38 (95% confidence interval (CI): 0.30-0.45, p<0.0001) in boys and 0.18 (95% CI: 0.12-0.25, p<0.0001) in girls after 1.5 years of treatment, independently of baseline age, BMI SDS, and Tanner stage (all p>0.08). WC was reduced by a mean of 3.8 cm (95% CI: 2.7-4.9, p>0.0001) in boys and 5.1 cm (95% CI: 4.0-6.2, p>0.0001) in girls. The dropout rate was 31% after 1.5 years. A median of 4.5 consultation hours was invested per child per year. CONCLUSION: BMI SDS and WC were reduced after 1.5 years of treatment. Hence, this community-based overweight and obesity treatment program may help accommodate the need for improvements in treatment availability and accessibility.

Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study.

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 (ß = -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.

The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity.

The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring.

Neonatal anthropometrics and body composition in obese children investigated by dual energy X-ray absorptiometry.

UNLABELLED: Epidemiological and animal studies have suggested an effect of the intrauterine milieu upon the development of childhood obesity. This study investigates the relationship between body composition measured by dual energy X-ray absorptiometry expressed as body fat percent, body fat mass index (BFMI), and fat free mass index (FFMI) in obese children and the preceding in utero conditions expressed by birth weight, birth length, and birth weight for gestational age. The study cohort consisted of 776 obese Danish children (median age 11.6 years, range 3.6-17.9) with a mean Body Mass Index Standard Deviation Score (BMI SDS) of 2.86 (range 1.64-5.48) treated in our national referral centre. In a linear general regression model adjusted for age, gender, socioeconomic status, and duration of breastfeeding, we found the body fat percent, FFMI, and BFMI at the time of enrolment in childhood obesity treatment to be significantly correlated with both birth weight and birth weight for gestational age. CONCLUSION: These results indicate a prenatal influence upon childhood obesity. Although there are currently no sufficient data to suggest any recommendations to pregnant women, it is possible that the prenatal period may be considered as a potential window of opportunity for prevention of childhood overweight and obesity.

Changes in lipidemia during chronic care treatment of childhood obesity.

BACKGROUND: Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents. METHODS: A total of 240 obese children and adolescents (median age, 11.3 years; range, 3.9-20.9) were enrolled in a best-practice multidisciplinary chronic care treatment program. The concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) and anthropometric data comprising height and weight were collected at baseline and after up to 39 months of continuous treatment. RESULTS: The BMI standard deviation score (SDS) decreased in 51% of patients and maintained unchanged in 32% of patients during the treatment. At baseline, 65 (27.1%) of the patients exhibited dyslipidemia defined as increased concentrations of total cholesterol (>200 mg/dL), LDL (>130 mg/dL), or TGs (>150 mg/dL), or decreased HDL concentration (<35 mg/dL). Dyslipidemia improved with weight loss; the odds ratio (OR) was 0.37 per BMI SDS (p = 0.014) after adjusting for age, sex, and baseline BMI SDS. Baseline TG concentration correlated positively and HDL concentration correlated negatively with baseline BMI SDS. Weight loss was associated with a decrease in the concentrations of total cholesterol (p = 0.0005), LDL (p < 0.0001), non-HDL (p < 0.0001), and TGs (p < 0.0001), and with an increase in HDL concentration (p < 0.0001). CONCLUSION: High lipid concentrations were associated with childhood obesity. The lipid profile improved during weight loss independently of the baseline BMI SDS and baseline lipid concentration.