This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children.
Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years.
In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol.
Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.
Cites: Child Obes. 2012 Dec;8(6):533-4123181919
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Cites: Int J Obes (Lond). 2014 Jan;38(1):40-523828099
Treating severe childhood obesity has proven difficult with inconsistent treatment results. This study reports the results of the implementation of a childhood obesity chronic care treatment protocol.
Patients aged 5 to 18 years with a body mass index (BMI) above the 99th percentile for sex and age were eligible for inclusion. At baseline patients' height, weight, and tanner stages were measured, as well as parents' socioeconomic status (SES) and family structure. Parental weight and height were self-reported. An individualised treatment plan including numerous advices was developed in collaboration with the patient and the family. Patients' height and weight were measured at subsequent visits. There were no exclusion criteria.
Three-hundred-thirteen (141 boys) were seen in the clinic in the period of February 2010 to March 2013. At inclusion, the median age of patients was 11.1 years and the median BMI standard deviation score (SDS) was 3.24 in boys and 2.85 in girls. After 1 year of treatment, the mean BMI SDS difference was -0.30 (95% CI: -0.39; -0.21, p
Cites: Am J Clin Nutr. 2010 May;91(5):1165-7120219965
A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS53) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS53 might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents.
We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children by linear regressions using an additive genetic model.
In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (ß?=?0.109?±?0.050 (SE); p?=?2.73?×?10-2), fasting plasma glucose (ß?=?0.010?±?0.005 mmol/l; p?=?2.51?×?10-2) and systolic BP SD score (ß?=?0.026?±?0.012; p?=?3.32?×?10-2) as well as lower HDL-cholesterol (ß?=?-0.008?±?0.003 mmol/l; p?=?1.23?×?10-3), total fat-mass percentage (ß?=?-0.143?±?0.054%; p?=?9.15?×?10-3) and fat-mass percentage in the legs (ß?=?-0.197?±?0.055%; p?=?4.09?×?10-4). In the population-based sample of children, the GRS53 only associated with lower HDL-cholesterol concentrations (ß?=?-0.007?±?0.003 mmol/l; p?=?1.79?×?10-2).
An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.
Clinically-relevant protocols for the treatment of childhood obesity are lacking. This study report results for a clinic-based structured treatment program for chronic childhood obesity.
Patients were measured at baseline and for up to 24 months; there were no prior eligibility criteria. At baseline, height, weight, Tanner stages, testicular size, time of menarche, and social class of the parents were registered. A structured, tailored treatment plan including best-practice-based interventions was initiated. Height, weight, and pubertal development were measured at subsequent visits.
A total of 617 children or youths were included; 325 were girls and 292 were boys. At entry, the mean age was 11.6 years and the mean body mass index (BMI) standard deviation score (SDS) was 3.0. Seventy stopped treatment, 547 were in treatment, 125 had 1 examination, and 492 had two or more examinations, with a mean visit interval of six weeks. After 12 months, the mean BMI SDS decreased by 0.23 (P
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.
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.
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).
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.
In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 substrates in obese versus non-obese children.
The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which will be defined by using well-tested probes; midazolam, chlorzoxazone and caffeine. Each of the probes will be administered as a single dose. Subsequently, blood and urine samples will be collected at pre-specified times.
The aim of the CYTONOX trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 in obese and non-obese children. The results are expected to be used in the future as a basis for drug dosing recommendations in obese children.
The study was funded by the Danish Regions' "Medicinpuljen". The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Overweight children are at an increased risk of becoming obese adults, which may lead to shorter life expectancies in the current generation of children as compared to their parents. Furthermore, being an overweight child has a negative psycho-social impact. We consider obesity in children and adolescents a chronic illness, which is in line with the American Medical Society. We summarize the evidence for the efficacy of a combination of diet, physical activity and behavior-focused interventions in a family-based setting. The present guidelines propose a multidisciplinary service implemented as a "chronic care model" based on "best clinical practice" inspired by an American expert committee and the daily practice of The Children's Obesity Clinic at Copenhagen University Hospital Holbaek. Children and adolescents should be referred for examination and treatment in a pediatric setting when BMI corresponds to an isoBMI of minimum 30 or BMI corresponds to an isoBMI of 25 and complex obesity is suspected. Obtaining a thorough medical history is pivotal. We propose a structured interview to ensure collection of all relevant information. We recommend physical examination focused on BMI, waist circumference, growth, pubertal stage, blood pressure, neurology and skin and provide comprehensive paraclinical investigations for obesity and obesity related conditions. Treatment of obesity in children and adolescents is fully dependent on the combined effort of the entire family. This cannot be overemphasized! The main principle of the treatment is developing an individual detailed plan for every patient to reduce caloric intake whilst increasing physical activity, leaving no ambiguity with the recommendations.
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.
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.
In the population-based cohort, plasma concentrations of total cholesterol (TC) (P
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.
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.
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.
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
Cites: J Clin Res Pediatr Endocrinol. 2016 Mar 5;8(1):26-3126758817
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.
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.
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?