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1.
J Pediatr Endocrinol Metab ; 32(12): 1351-1358, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31714888

RESUMO

Background The association between thyroid-stimulating hormone (TSH) concentrations and blood pressure is well described in adults, but only studied to a limited extent in children and adolescents and almost entirely in population-based cohorts. The present study investigates the association between TSH and blood pressure, and the influence of leptin and adiponectin, in a cohort of children and adolescents enrolled in obesity treatment compared with a population-based cohort. Methods We studied 4154 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort from The Danish Childhood Obesity Data- and Biobank. Anthropometrics, blood pressure and biochemical markers, including TSH, leptin and adiponectin concentrations, were collected. Adjusted correlation and interaction analyses were performed. Results Patients from the obesity clinic cohort exhibited higher concentrations of TSH and higher blood pressure than participants from the population-based cohort. TSH standard deviation scores (SDS) were significantly associated with all blood pressure-related variables in the population-based cohort, but only with systolic blood pressure SDS and hypertension in the obesity clinic cohort. The interaction between TSH SDS and adiponectin was found to be independently associated with systolic blood pressure and hypertension in the population-based cohort only. Conclusions The significant associations between TSH, adiponectin and blood pressure, observed in children and adolescents from a population-based cohort, are attenuated or absent in children and adolescents with overweight or obesity, suggesting that childhood obesity distorts the healthy interplay between the thyroid axis, thyroid-adipokine interaction and blood pressure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31693771

RESUMO

AIM: This study investigates the prevalence of disturbed eating behaviours in children and adolescents initiating obesity treatment, and how the prevalence varies with age, sex and body mass index (BMI) standard deviation score (SDS). Secondly, it examines whether the presence of disturbed eating behaviours at enrolment is associated with the degree of weight loss after 12 months of treatment. METHODS: A total of 3621 patients aged 3-18 years enrolled in a multidisciplinary obesity treatment programme were studied. Follow-up data after a median of 12.4 months were available for 2055 patients. Upon entry, patients were assessed for the following disturbed eating behaviours: meal skipping, emotional eating, overeating and rapid eating. Height and weight were measured at baseline and follow-up. RESULTS: At enrolment, median age was 11.4 years, median BMI SDS was 2.87, and 82.2% of patients exhibited one or more disturbed eating behaviours. The prevalence of meal skipping, emotional eating and rapid eating increased with age (P < 0.01). Patients who reported overeating or rapid eating exhibited a 0.06-0.11 higher BMI SDS at enrolment than patients without these disturbed eating behaviours (P < 0.02). After 1 year of treatment, BMI SDS was reduced in 75.7% of patients, and the median reduction was 0.24 (95% confidence interval: 0.22-0.27). Overeating was associated with a higher degree of weight loss, while meal skipping, emotional eating and rapid eating did not associate with the degree of weight loss at follow-up. CONCLUSIONS: Disturbed eating behaviours were highly prevalent in children and adolescents with overweight or obesity, and varied with age and sex. After 1 year of treatment, the degree of obesity improved, regardless of the presence of disturbed eating behaviours at treatment initiation.

3.
Clin Pharmacokinet ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745864

RESUMO

BACKGROUND: Midazolam is a first-line drug for the treatment of status epilepticus, both by buccal and intravenous administration. In children and adolescents with obesity, midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics of midazolam, after intravenous administration, in obese and non-obese adolescents aged 11-18 years. METHODS: All trial participants received a 1-µg midazolam microdose as an intravenous bolus. 13 blood samples were collected per participant at pre-specified timepoints. Plasma concentration-time data were fitted to pharmacokinetic models using non-linear mixed-effects modeling. Covariates such as weight, age, and body mass index standard deviation score were tested to explain the inter-individual variability associated with the pharmacokinetic parameters. RESULTS: Sixty-seven adolescents were included in the analysis. The pharmacokinetics of midazolam was best described with a two-compartment model. The rate of distribution was faster, and the peripheral volume of distribution was larger in adolescents with a high body mass index standard deviation score compared with adolescents with a lower standard deviation score. Simulations revealed that long-term infusions based on total body weight could lead to high plasma concentrations in adolescents with obesity. Furthermore, simulated plasma concentrations after a fixed buccal dose indicated that adolescents with obesity may be at risk of sub-therapeutic midazolam plasma concentrations. CONCLUSIONS: The body mass index standard deviation score was shown to have a significant influence on the peripheral volume of distribution and the inter-compartmental clearance of midazolam. The current dosing guidelines for status epilepticus, where the midazolam dose is adjusted to total body weight or age, may lead to supra- and sub-therapeutic plasma concentrations, respectively, in adolescents with obesity. TRIAL REGISTRATION: EudraCT: 2014-004554-34.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31617910

RESUMO

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 two cohorts of Danish children and adolescents: 1,858 from a population-based cohort, and 2,155 with overweight or obesity, aged between six and 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.

5.
J Bone Miner Metab ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471646

RESUMO

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (- 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001-0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

6.
Hum Mol Genet ; 28(19): 3327-3338, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504550

RESUMO

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

7.
Am J Clin Nutr ; 110(5): 1079-1087, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504107

RESUMO

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 (ß = 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: ß = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: ß = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: ß = 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 (ß = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (ß = -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.

8.
Int J Dermatol ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498890

RESUMO

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.

9.
Int J Obes (Lond) ; 43(10): 2007-2016, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332278

RESUMO

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 WHRadjBMI 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.

10.
Pediatr Diabetes ; 20(5): 538-548, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31074070

RESUMO

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.

11.
Int J Pediatr Otorhinolaryngol ; 123: 57-62, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075707

RESUMO

OBJECTIVES: To evaluate the impact of weight-loss management on obstructive sleep apnea (OSA) in children and adolescents with obesity. We hypothesized that a reduction in the degree of obesity was associated with a reduction in the apnea-hypopnea index (AHI). METHODS: OSA (AHI ≥2) was investigated using a type 3 portable sleep device (Nox T3) in children and adolescents aged 7-18 years with overweight or obesity (body mass index standard deviation score (BMI SDS) > 1.28) at enrollment in a chronic care multidisciplinary overweight- and obesity treatment clinic. Individuals with OSA were included prospectively and longitudinally. A follow-up sleep examination was performed after 6 and 12 months from baseline accompanied by anthropometric measurements. RESULTS: At baseline, 62 children with OSA were included (median age = 13.4 years, median BMI SDS = 3.16). A total of 55 out of 62 children (89%) attended the first follow-up, and 29 out of 34 children (85%) with residual OSA attended the second follow-up. By the end of the study, the AHI was normalized in 27 out of 62 children (44%). In a multiple linear regression analysis, the decrease in BMI SDS was associated with the decrease in AHI upon the first follow-up (p = 0.02) independently of sex; age; baseline puberty stage; baseline tonsillar hypertrophy; baseline AHI; baseline BMI SDS; and time to follow-up. There was no association between change in BMI SDS and change in AHI from the first to the second follow-up (p = 0.81). CONCLUSIONS: OSA improved during obesity treatment, and the reduction in BMI SDS was significantly associated with the reduction in AHI after approximately six months of treatment. This indicates that obesity treatment should be considered among the first-line treatments of OSA in children and adolescents affected by overweight or obesity.


Assuntos
Obesidade/complicações , Obesidade/terapia , Apneia Obstrutiva do Sono/complicações , Perda de Peso , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Polissonografia , Índice de Gravidade de Doença , Programas de Redução de Peso
12.
Pregnancy Hypertens ; 15: 78-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30825932

RESUMO

OBJECTIVE: Preeclampsia (PE) is a serious complication of pregnancy, the pathogenesis of which is largely unknown. We hypothesize that adipocytokines may play a role in the pathogenesis of PE, particularly in obese women, and evaluate leptin and adiponectin as potential first trimester markers for predicting PE. STUDY DESIGN: A cohort of 2503 pregnancies, containing 93 PE pregnancies, was divided into women with normal weight, moderate, or severe obesity. All pregnancies had serum adiponectin and leptin measured in first trimester. Logistic regression was used to model PE with maternal characteristics and concentrations of the biomarkers. RESULTS: In obese women a lower concentration of adiponectin was found in PE pregnancies; the concentration was lowest in the severely obese (p = 0.005). No association was found in normal weight women (p = 0.72). Leptin concentration had no association with PE in normal weight and moderately obese (p = 0.175-0.072), however in women with severe obesity a lower level of leptin was found (p = 0.049). The AUC was 0.73 for the ROC curve of combined maternal characteristics and adiponectin. Using adiponectin in women with moderate to severe obesity the sensitivity was 72.9% and the specificity was 49%. CONCLUSIONS: In severely obese women, PE is associated with low serum adiponectin and leptin concentrations in first trimester. This indicates that the inability of adipokine regulation to adapt to severe obesity may play a role in the pathogenesis of PE. Adipocytokines may contribute in identification of risk pregnancies among severe obese.


Assuntos
Adiponectina/sangue , Leptina/sangue , Obesidade/sangue , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Idade Gestacional , Humanos , Modelos Logísticos , Obesidade/complicações , Pré-Eclâmpsia/etiologia , Gravidez , Primeiro Trimestre da Gravidez/sangue , Medição de Risco , Adulto Jovem
13.
Scand J Clin Lab Invest ; 79(1-2): 129-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30861348

RESUMO

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.


Assuntos
Jejum/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Fatores Etários , Índice de Massa Corporal , Criança , Estudos de Coortes , Europa (Continente) , Grupo com Ancestrais do Continente Europeu , Feminino , Voluntários Saudáveis , Humanos , Imunoensaio , Luminescência , Masculino , Valores de Referência , Fatores Sexuais , Adulto Jovem
14.
Clin Chim Acta ; 493: 123-128, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30849308

RESUMO

BACKGROUND: Leptin and adiponectin are two key adipocyte secreted hormones and both are involved in several essential physiological mechanisms. Due to their central role in energy homeostasis their ratio, the leptin/adiponectin ratio, is believed to be a marker of metabolic derangement. Pediatric reference values are needed for the risk stratification of individual-measured ratios. METHODS: Blood samples were drawn from healthy, Danish schoolchildren following an overnight fast. A ratio was calculated from serum leptin and adiponectin quantifications done using commercially available ELISA Kits. RESULTS: Nine hundred eighty-three participants (583 girls) aged 6-18 years were included. Smoothed percentile curves and age-group specific percentiles were calculated. A correlation with age was demonstrated, with a gradual increase with age in girls and a negative parabolic relation, with a peak in age group 10-14, in boys. The leptin/adiponectin ratio was positively correlated to the body mass index standard deviation score for both girls and boys (p < .001). CONCLUSION: The leptin/adiponectin ratio is correlated to age and differs between the sexes in healthy children and adolescents.


Assuntos
Adiponectina/normas , Leptina/normas , Adiponectina/sangue , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Leptina/sangue , Masculino , Valores de Referência
15.
Eur Arch Otorhinolaryngol ; 276(3): 871-878, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30689039

RESUMO

PURPOSE: To investigate the prevalence of obstructive sleep apnea (OSA) in children referred for obesity treatment, and to compare the prevalence with that of a normal-weight group. Moreover, we examined the association between Body Mass Index Standard Deviation Score (BMI SDS) and the Apnea-Hypopnea Index (AHI). METHODS: This cross-sectional study included 139 children aged 7-18 years with overweight/obesity (BMI SDS >1.28) recruited from an obesity treatment clinic. The normal-weight group consisted of 33 children (BMI SDS ≤ 1.28) aged 7-18 years recruited from schools. Sleep examinations were performed using a type 3 portable sleep monitor (Nox T3). OSA was defined as AHI ≥ 2. Height and weight were measured and the tonsillar size was clinically estimated using the Brodsky scale. RESULTS: The OSA prevalence was 44.6% in children with overweight/obesity compared with 9.1% in the normal-weight group (p = 0.0002), and the relative risk of OSA was 4.9 (95% CI 1.6-14.7). In a logistic regression, a one-unit increase in the BMI SDS increased the odds of having OSA by a factor of 1.92 independent of age, sex, tonsillar hypertrophy, and asthma (95% CI 1.33-2.76, p = 0.0005). A generalized linear regression adjusted for the same variables revealed an association between BMI SDS and AHI (a one-unit increase in the BMI SDS equaled an average increase in the AHI of 35% (95% CI 19-53%, p < 0.0001)). CONCLUSIONS: In this study, children with overweight/obesity had a significantly higher prevalence of OSA compared with a normal-weight group. Increased BMI SDS was associated with increased AHI.


Assuntos
Sobrepeso/epidemiologia , Obesidade Pediátrica/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Tonsila Faríngea/patologia , Adolescente , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Hipertrofia/epidemiologia , Modelos Logísticos , Masculino , Tonsila Palatina/patologia , Polissonografia , Prevalência
17.
Obesity (Silver Spring) ; 26(12): 1915-1922, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30460774

RESUMO

OBJECTIVE: This study aimed to investigate the effect of a genetic risk score (GRS) comprising 15 single-nucleotide polymorphisms, previously shown to associate with childhood BMI, on the baseline cardiometabolic traits and the response to a lifestyle intervention in Danish children and adolescents. METHODS: Children and adolescents with overweight or obesity (n = 920) and a population-based control sample (n = 698) were recruited. Anthropometric and biochemical measures were obtained at baseline and in a subgroup of children and adolescents with overweight or obesity again after 6 to 24 months of lifestyle intervention (n = 754). The effects of the GRS were examined by multiple linear regressions using additive genetic models. RESULTS: At baseline, the GRS associated with BMI standard deviation score (SDS) both in children and adolescents with overweight or obesity (ß = 0.033 [SE = 0.01]; P = 0.001) and in the population-based sample (ß = 0.065 [SE = 0.02]; P = 0.001). No associations were observed for cardiometabolic traits. The GRS did not influence changes in BMI SDS or cardiometabolic traits following lifestyle intervention. CONCLUSIONS: A GRS for childhood BMI was associated with BMI SDS but not with other cardiometabolic traits in Danish children and adolescents. The GRS did not influence treatment response following lifestyle intervention.

18.
Diabetologia ; 61(8): 1769-1779, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29855666

RESUMO

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS/INTERPRETATION: 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.

19.
Cell Metab ; 28(1): 23-32.e3, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29861388

RESUMO

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.

20.
Pharmacol Res Perspect ; 6(3): e00398, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29721323

RESUMO

Obesity can affect the pharmacokinetics of most drugs, which may result in under- or overdosing if traditional pediatric dosing strategies are used. To investigate currently applied dosage strategies in children with overweight or obesity (overweight/obesity), in a clinical treatment facility. In particular, whether dosing guidelines were available and metrics of body size applied. A retrospective cohort study of 200 patients admitted to the Danish Children's Obesity Clinic. Data were collected from 2007 to 2015. Overweight/obese children 3-18 years were included if they had at least one drug prescription. Overall there were 658 prescriptions, primarily analgesics, psychotropics, asthma medications, and antibiotics. Except for one prescription, guidelines for dosage of overweight/obese children were not available in the clinic. In one prescription of gentamicin, the dose was adjusted by a metric body size. Otherwise dose was predominately prescribed either by total body weight or as fixed dose by age, in accordance with the recommendations of normal weight children. In drugs with a narrow therapeutic interval, we found large interindividual variations in dosing regimens, that is, for gentamicin, paracetamol, and prednisolone. Reduction of dose to the maximum recommended adult dose was common practice, when the dose calculated by total body weight (ie, mg/kg) exceeded this maximum. This study highlights the shortage of dosing guidelines in overweight/obese children. We found a large interindividual variability in dosage regimens, even in drugs with narrow therapeutic intervals. The clinicians rely on "best practice", as evidence-based dosage regimens are missing for many drugs prescribed during childhood.

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