Body Mass Index Standard Deviation Score Research Articles

Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity

BackgroundWith the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. Objectives. The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD.MethodsData were collected from 428 children and adolescents aged 6-16 years recruited from the Children’s Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes.ResultsAmong 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance.ConclusionsThe prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.

Asprosin serum levels and glucose homeostasis in children with obesity

PurposeAsprosin is a novel adipokine involved in glucose homeostasis, food intake regulation and energy homeostasis. However, the role of asprosin in glucose homeostasis regulation remains still controversial, especially in pediatrics. Aims of the study were to compare fasting serum asprosin levels between obese children and controls and to investigate the relationships of asprosin with body mass index (BMI) and biochemical markers of insulin resistance, insulin sensitivity, β-cell function and cardio-metabolic risk in obese non-diabetic children. MethodsThis cross-sectional, case-controlled, study included 43 obese children and 24 lean matched controls consecutively recruited. Children underwent clinical and biochemical assessments, including oral glucose tolerance test. Fasting asprosin serum levels were measured using an enzyme-linked immunosorbentassay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), Matsuda-index, Insulinogenic-index, Areas Under the Curves for glucose and insulin were calculated. Successively, asprosin variable was dichotomized according to mean value in order to create two ordered classes of values. ResultsFasting asprosin concentration was significantly lower in obese children compared to controls (331.9 ± 120.5 vs 358.1 ± 74.1 pg/ml; p = 0.013). Asprosin was lower in boys than in girls (313.7 ± 59.5 vs 361.1 ± 127.2 pg/ml; p = 0.044), while BMI standard deviation score (SDS) was higher in boys compared to girls (p = 0.024). Asprosin was negatively correlated with BMI (p = 0.024), BMI SDS (p = 0.044) and male sex (p = 0.043) in the entire cohort. No significant differences in asprosin levels were demonstrated between insulin resistant and non-insulin resistant obese children. Logistic regression models documented a significant negative association between BMI SDS and dichotomized asprosin. In particular, higher BMI SDS values were associated to lower asprosin serum levels class. A receiver operating characteristic (ROC) analysis showed existence of the best cut-off for BMI SDS (+2.7 SDS) variable into discriminating patients belonging to two asprosin classes in our cohort. ConclusionsIn conclusion, asprosin serum levels were significantly lower in obese children compared to control.Fasting asprosin decreased with increasing BMI, but it was not significantly affected by IR.

Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes

Objective:The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM.Methods:The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated.Results:Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001).Conclusion:In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.

Evaluation of Body Composition in Paediatric Osteogenesis Imperfecta

Osteogenesis Imperfecta (OI) is a skeletal disorder characterised by a predisposition to recurrent fractures and bone deformities. Clinically OI is defined by features such as short stature, however, less is known regarding body composition. Assess body composition, both lean mass and fat mass, in a paediatric OI population. Children with OI attending the Bone service at the Royal Hospital for Children Glasgow were included; who had a dual-energy x-ray absorptiometry (DXA) scan performed 2015-2018. Height and body-mass-index (BMI) were converted to standard-deviation scores (SDS) using UK population references. DXA-derived lean mass and fat mass were used to generate lean-mass-index (LMI) and fat-mass-index (FMI) by dividing the covariates by height squared. LMI and FMI were converted to age-and-gender-adjusted SDS using DXA data from 198 local healthy children. Thirty-eight children (20 males) with median age 11.95 (range: 4.8, 18.3) years were included. Median height SDS was -1.08 (-3.64, 1.62) and was significantly lower than the healthy population (p<0.0001). Median BMI SDS was -0.10 (-2.31, 2.95), and not significantly different from the healthy population (p = 0.53). Median LMI SDS was -2.52 (-6.94, 0.77), and significantly lower than healthy controls (p<0.0001); 61% (23/38) had an SDS below -2.0. Median FMI SDS was 0.69 (-0.45, 2.72), significantly higher than healthy controls (p < 0.0001). BMI SDS cut-offs of -0.15 and 1.33, from ROC analysis, identified children with LMI SDS <-2, with a positive predictive value of 95% and a negative predictive value of 70%; and FMI SDS >2 with a positive predictive value of 44% and a negative predictive value of 100%. A contemporary population of children with ranging severities of OI present with significant reduction in height and lean mass, and relatively high fat mass. Standard BMI SDS cut-offs for identifying children with malnutrition and obesity have poor prognostic validity in OI.

The association between body mass index and brain morphology in children: a population-based study

Brain morphology is altered in both anorexia nervosa and obesity. However, it is yet unclear if the relationship between Body Mass Index-Standard Deviation Score (BMI-SDS) and brain morphology exists across the BMI-SDS spectrum, or is present only in the extremes. The study involved 3160 9-to-11 year-old children (50.3% female) who participate in Generation R, a population-based study. Structural MRI scans were obtained from all children and FreeSurfer was used to quantify both global and surface-based measures of gyrification and cortical thickness. Body length and weight were measured to calculate BMI. Dutch growth curves were used to calculate BMI-SDS. BMI-SDS was analyzed continuously and in two categories (median split). The relationship between BMI-SDS (range − 3.82 to 3.31) and gyrification showed an inverted-U shape curve in children with both lower and higher BMI-SDS values having lower gyrification in widespread areas of the brain. BMI-SDS had a positive linear association with cortical thickness in multiple brain regions. This study provides evidence for an association between BMI-SDS and brain morphology in a large sample of children from the general population and suggests that a normal BMI during childhood is important for brain development. Future studies could determine whether lifestyle modifications optimize BMI-SDS result in return to more typical patterns of brain morphology.

Association between serum uric acid and triglycerides in Chinese children and adolescents with short stature

BackgroundElevated triglyceride (TG) levels are a biomarker for cardiovascular disease (CVD) risk. The correlation between serum uric acid (SUA) and TG concentrations in adults or obese children is well established. However, studies on SUA and TG in children with short stature are limited.AimTo determine the relationship between SUA and TG levels in short children and adolescents.MethodThis was a cross-sectional evaluation of a cohort of 1095 patients with short stature (720 males and 375 females). The related clinical characteristics, including anthropometric and biochemical parameters, were determined.ResultsSmooth curve fitting, adjusted for potential confounders was performed, which indicated the existence of a non-linear relationship between these measures. Piecewise multivariate linear analysis revealed a significant positive relationship between SUA and TG at SUA concentrations over 7 mg/dL (β = 0.13, 95% CI: 0.05–0.22, P = 0.002) but no significant correlation at lower SUA levels (β = 0.01, 95% CI: 0.01–0.04, P = 0.799). Furthermore, a stratified analysis was performed to appraise changes in this relationship for different sexes and standard deviation levels of body mass index (BMI). The non-linear relationship remained consistent in males and females with BMI standard deviation scores (BMI SDS) ≥ 0, with inflection points of 6.71 mg/dL and 3.93 mg/dL, respectively. Within these two groups, SUA and TG levels showed a positive association when SUA levels were higher than the inflection point (β = 0.21, 95% CI: 0.11–0.31, P < 0.001 for males and β = 0.1, 95% CI: 0.03–0.17, P = 0.005 for females). However, a specific relationship was not observed at lower SUA levels. No significant relationships were found between SUA and TG levels in males and females with BMI SDS < 0.ConclusionThe present study identified the non-linear association of SUA and TG levels with short children and adolescents. This relationship was based on BMI status. This finding suggests that health status should be considered for short stature children with high SUA levels, especially in children with a high BMI standard deviation score.

Changes in body composition and cardiometabolic risk factors in relation to the reduction in body mass index in adolescents with obesity.

Introduction: there are controversial data in relation to the reduction in body mass index standard deviation score (BMI-SDS) needed to improve adiposity in the pediatric population with obesity. The aim of this work was to determine the minimum variation in BMI-SDS required to improve the values of adiposity markers and cardiometabolic risk factors in growing adolescents with obesity. Methods: a longitudinal study consisting of clinical evaluation (waist circumference, waist-to-height ratio, fat mass index, and blood pressure) and blood testing (insulin resistance and lipid profile) was conducted in 350 adolescents with obesity (152 boys and 198 girls) aged 10.2-14.3 years who went through a combined intervention (12 months). Results: a decrease in SDS-BMI ≤ 0.5 was not associated with any significant improvement in the clinical features and blood testing recorded. A decrease in BMI-SDS > 0.5, and especially if > 1.0, was linked to a significant improvement in adiposity markers. A decrease in BMI-SDS > 0.5 was associated with a significant improvement in insulin resistance, and a decrease in BMI-SDS > 1.0 was associated with a significant decrease in the percentage of patients who showed high values of systolic blood pressure, HOMA-IR, and lipid profile Conclusions: improvement in body composition, insulin resistance, and lipid profile can be observed with reductions in BMI-SDS ≥ 0.5 in obese adolescents, while extended benefits are obtained by losing at least 1.0 BMI-SDS.

Mediating Effects of Mental Health Problems in a Clinical Sample of Adolescents with Obesity

Introduction: The prevalence rates of obesity have increased in recent decades; despite leveling off in recent German studies among children and adolescents, obesity rates remain high. Psychosocial factors have an adverse impact on the maintenance of obesity. Hence, this study examined the mediating effects of mental health problems on the relation between the body mass index standard deviation score (BMI-SDS) and global health-related quality of life (HRQoL) among adolescent inpatients with obesity while controlling for gender and age-group. Methods: Three simple mediation analyses with gender and age-group as covariates were conducted for n = 313 adolescents with obesity (n_female = 193, 61.7%) aged 12–17 (M = 14.19, SD = 1.52; BMI-SDS: M = 2.67, SD = 0.52). The adolescents were asked to report their global HRQoL at admission, and their parents estimated the children’s mental health problems at home prior to inpatient rehabilitation. Results: Emotional, peer-related, and conduct problems mediated the unfavorable effects of BMI-SDS on global HRQoL, showing high, moderate, and small effect sizes, respectively (completely standardized indirect effect of emotional problems: β = −0.09, SE = 0.03, 95% B-CI = −0.15 to −0.04; conduct problems: β = −0.03, SE = 0.02, 95% B-CI = −0.06 to −0.01; peer-related problems: β = −0.10, SE = 0.03, 95% B-CI = −0.16 to −0.05). Conclusion: Mental health problems may be one salient pathway through which BMI-SDS impairs global HRQoL among adolescents with obesity. Hence, inpatient rehabilitation programs for adolescents with obesity should increase their focus more on the development of psychosocial skills. Thus, the promotion of emotion regulation and social-emotional competencies is suggested.

Liraglutide for overweight and obesity

Liraglutide for overweight and obesity

A lifestyle pattern during adolescence is associated with cardiovascular risk markers in young adults: results from the DONALD cohort study.

Lifestyle score approaches combining individual lifestyle factors, e.g. favourable diet, physical activity or normal body weight, showed inverse associations with cardiovascular disease (CVD) risk. However, research mainly focussed on adult behaviour and is scarce for vulnerable time windows for adult health like adolescence. We investigated associations between an adolescent lifestyle score and CVD risk markers in young adulthood. Overall, we analysed 270 participants of the open DONALD cohort study with 1-6 complete measurements of five lifestyle factors (healthy diet, moderate-to-vigorous physical activity, sedentary behaviour, sleep duration and BMI standard deviation score) during adolescence (females: 8⋅5-15⋅5 years and males: 9⋅5-16⋅5 years). Multivariable linear regression models were used to investigate the prospective association between the adolescent lifestyle score (0-5 points) and CVD risk markers in young adulthood (18-30 years). On average, participants obtained a mean adolescent lifestyle score of 2⋅9 (0-5) points. Inverse associations between the adolescent lifestyle score and waist circumference, waist-to-height ratio and percentage of body fat were observed (4⋅1, 4⋅1 and 9⋅2 % decrease per 1 point increase in adolescent lifestyle score, respectively, P < 0⋅05). For the remaining CVD risk markers (glucose, blood lipids, blood pressure and a proinflammatory score), no associations were observed. A healthy adolescent lifestyle is particularly associated with CVD risk-related favourable anthropometric markers in adulthood. A more comprehensive understanding of lifestyle patterns in the life course might enable earlier, targeted preventive measures to assist vulnerable groups in prevention of chronic diseases.

Dietary taste patterns in early childhood: the Generation R Study

ABSTRACTBackgroundTaste preference is an important determinant of dietary intake and is influenced by taste exposure in early life. However, data on dietary taste patterns in early childhood are scarce.ObjectivesWe aimed to evaluate dietary taste patterns in early childhood, to examine their tracking between the ages of 1 and 2 y, and to examine their associations with socioeconomic and lifestyle factors.MethodsDietary intake of children participating in a population-based cohort was assessed with a 211-item age-specific FFQ at the ages of 1 y ( n = 3629) and 2 y (n = 844) (2003–2007). Taste intensity values of FFQ food items were calculated based on a food taste database that had been previously constructed and evaluated using a trained adult sensory panel. Cluster analysis based on taste values identified 5 taste clusters that we named: “neutral,” “sweet and sour,” “sweet and fat,” “fat,” and “salt, umami and fat.” Linear regression models were used to examine associations of percentage energy (E%) intake from these taste clusters with socioeconomic and lifestyle factors.ResultsAt the age of 1 y, 64% ± 13% (mean ± SD) of energy intake was obtained from the “neutral” cluster, whereas at age 2 y, this was 42% ± 8%. At age 2 y, children had higher energy intakes from the “sweet and fat” (18% ± 7%), “fat” (11% ± 4%), and “salt, umami, and fat” (18% ± 6%) clusters than at age 1 y (7% ± 6%, 6% ± 4%, and 11% ± 6%, respectively). In multivariable models, older maternal age, longer breastfeeding duration, and later introduction of complementary feeding were associated with more energy from the “neutral” cluster (e.g., β: 0.31 E%; 95% CI: 0.19, 0.43 E% per 1 mo longer breastfeeding). Higher child BMI was associated with more energy from the “salt, umami, and fat” cluster (β: 0.22 E%; 95% CI: 0.06, 0.38 E% per BMI standard deviation score).ConclusionsDietary taste patterns in this Dutch cohort were more varied and intense in taste at age 2 y than at 1 y, reaching a level similar to that previously observed in Dutch adults. Important factors related to dietary taste patterns of young children are maternal sociodemographic factors and feeding practices.This trial was registered at trialregister.nl as NL6484.

Beyond Body Mass Index - Body Composition Assessment by Bioimpedance in Routine Endocrine Practice

ObjectiveTo explore the body composition of pediatric patients referred for endocrine evaluation. MethodsThis real-life observational study conducted between January 2018 and January 2020 included 10 001 clinic visits of 3500 children and adolescents; first visits of 5 to 18-year-old patients were included. Anthropometric data, blood pressure levels, pubertal status, and bioelectrical impedance analysis (BIA, Tanita MC-780 MA) were extracted from medical files. Excluded from the analysis were patients participating in other studies. ResultsA total of 1001 patients (48% boys, mean age 11.3 ± 3.4 years, 33.5% prepubertal) were included. Mean anthropometric z-scores were normal and similar for boys and girls. Sex differences in body composition were as follows: boys had lower fat percentage, lower truncal fat percentage, higher appendicular skeletal muscle mass, and a higher muscle-to-fat ratio (MFR) than girls (P < .001 for all). MFR correlated with body mass index-standard deviation scores (BMI-SDS) in overweight/obese patients (r = −0.558, P < .001), although not in underweight patients. Systolic blood pressure (SBP) correlated with BMI-SDS in overweight/obese patients (r = 0.262, P < .001), although not in underweight patients. Diastolic blood pressure (DBP) did not correlate with BMI-SDS in either group of extreme weight status. MFR correlated with SBP and DBP in overweight/obese patients (r = −0.230, P < .001 and r = −0.141, P = .018, respectively) as well as in underweight patients (r = 0.331, P < .001 and r = 0.264, P = .005, respectively). ConclusionsOur findings support BIA for a more refined characterization of patients referred for endocrine evaluation than BMI-SDS. MFR may be a better surrogate marker of blood pressure levels than BMI-SDS in both underweight and overweight/obese pediatric patients.

Effects of Fecal Microbiome Transfer in Adolescents With Obesity

Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.

Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5.

This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI). Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit. Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68±1.42 and 3.29±1.30 years respectively. Mean follow-up was 7.42±4.76 and 6.01±4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51±1.03 in CSII and-0.31±0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62±0.82 and 8.17±1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups. CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.

Fat distribution in short‐stature children born small for gestational age

Children born small for gestational age (SGA) with catch-up growth are at high risk for developing obesity; however, the characteristics of body composition, especially fat distribution, before and after growth hormone (GH) treatment in SGA children without catch-up growth remains largely unknown. Anthropometric characteristics, body composition by dual-energy X-ray absorption, and fat distribution by computed tomography at the umbilical level were examined in 27 prepubertal short-stature children born SGA before and 1year after GH treatment. Before GH treatment, short-stature SGA children had lean phenotypes, and both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were significantly lower than the age- and sex-matched Japanese reference values. Growth hormone treatment significantly increased height standard deviation scores (SDS), without affecting body mass index SDS. Percentage fat mass decreased with GH treatment; however, fat mass was not altered. Both VAT and SAT were significantly lower than the reference values after GH treatment. The ratio of VAT over SAT significantly increased by GH treatment. Both VAT and SAT were within or below the age- and sex-matched Japanese reference values in short-stature children born SGA before and after GH treatment, indicating that GH treatment may not have unfavorable effects on adiposity in short-stature children born SGA, although it may alter fat distribution.

Growth response and metabolic effects of growth hormone therapy in appropriate-for-gestational-age growth hormonedeficient children in relation to birth size and gestational age: A preliminary study.

The aim of the study was to investigate the influence of birth weight (BW), birth length (BL) and gestational age (GA) on growth pattern and metabolic profile in appropriate-for-gestational-age (AGA) growth hormone-deficient children before and during recombinant human growth hormone (rhGH) therapy. Forty children with isolated idiopathic growth hormone deficiency underwent auxological and biochemical assessment at baseline and after 6 and 12 months of rhGH therapy. Biochemical analysis included: insulin-like growth factor I (IGF-I), adiponectin, resistin, fasting glucose, fasting insulin, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and glycated haemoglobin (HbA1c). There was a tendency for positive association between BW and baseline height standard deviation score (SDS). GA correlated with baseline weight SDS (p=0.019) and BMI SDS (p=0.039). GA was associated with baseline fasting glucose (p=0.031), fasting insulin (p=0.027), HOMA-IR (p=0.010) and QUICKI (p=0.016). BW correlated with baseline HbA1c (p=0.032). After the initiation of rhGH therapy we did not find any significant relationships between birth size parameters or GA and metabolic profile of the studied children. In conclusion, our results suggest that AGA GH-deficient children born with higher birth size parameters and higher GA had better first-year growth response to rhGH therapy and better baseline metabolic profile, especially parameters of carbohydrate metabolism. In order to optimize the effects of rhGH therapy, higher rhGH doses should be considered in those GH-deficient children who were born with lower birth size and GA.

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7).ConclusionsThere were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome.

ObjectiveThe European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS).DesignOngoing, open-label, observational registry (NCT00903110).MethodsChildren and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008–2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs).ResultsHeight SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years’ treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common.ConclusionsIn most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.

The Prevalence of Nonalcoholic Fatty Liver Disease and Its Risk Factors in Children and Young Adults with Type 1 Diabetes Mellitus

To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and its associated risk factors in children and young adults with type 1 diabetes (T1D). A cross-sectional study was conducted at a tertiary care center in children and young adults with T1D. Liver fat quantification and hepatic fibrosis were assessed by magnetic resonance imaging proton density fat fraction and magnetic resonance elastography (MRE). Logistic regression analysis was performed to examine the associated risk factors for NAFLD. Fifty patients with T1D (28 females, 13 with overweight/obesity) were included. The median age and duration of T1D were 16.9years (IQR, 13.6-20years) and 6.5years (IQR, 4-11years), respectively. The prevalence of NAFLD was 10%. Four out of 5 patients with NAFLD were overweight/obese, and 2 had an and elevated alanine aminotransferase (ALT) level. None had liver fibrosis (defined as MRE >2.9kPa). Compared with patients without NAFLD, patients with NAFLD had significantly higher body mass index standard deviation score (BMI-SDS) (median, 0.94 [IQR, 1.30-2.62] vs 0.13 [IQR, -0.69 to 0.84]; P=.01), ALT (median, 17 IU/L [IQR, 16-52 IU/L] vs 12 IU/L [IQR, 10-14 IU/L]; P=.02), and lower high-density lipoprotein cholesterol (median, 49mg/dL [IQR, 41-51mg/dL] vs 57mg/dL [IQR, 52-69mg/dL]; P=.039). Multivariate logistic regression analysis identified high BMI-SDS as the sole independent risk factor associated with NAFLD (OR, 5.79; 95% CI, 1.04-32.18). The prevalence of NAFLD in children and young adults with T1D was comparable to that in the general population. Our study suggests that routine screening for NAFLD in patients with T1D might not be necessary but should be performed in those patients with T1D who are overweight/obese.

Serum Irisin Levels in Central Precocious Puberty and Its Variants.

The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context. A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels. Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ± 62.35 ng/mL; PP variants group: 529.60 ± 39.66 ng/mL; and control group: 325.03 ± 27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS. The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.