Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI − 6.1, − 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI − 11.2, − 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI − 4.6, − 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI − 6.7, − 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL β = 0.003, 95% CI − 0.01 to 0.002, p = 0.72). Conclusion: Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD

Change in adiposity is associated with change in glycoprotein acetyls but not hsCRP in adolescents with severe obesity.

BACKGROUND Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally. METHODS From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation. RESULTS All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR. CONCLUSION GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time

Sex and puberty-related differences in metabolomic profiles associated with adiposity measures in youth with obesity

BackgroundSpecific patterns of metabolomic profiles relating to cardiometabolic disease are associated with increased weight in adults. In youth with obesity, metabolomic data are sparse and associations with adiposity measures unknown.ObjectivesPrimary, to determine associations between adiposity measures and metabolomic profiles with increased cardiometabolic risks in youth with obesity. Secondary, to stratify associations by sex and puberty.MethodsParticipants were from COBRA (Childhood Overweight BioRepository of Australia; a paediatric cohort with obesity). Adiposity measures (BMI, BMI z-score, %truncal and %whole body fat, waist circumference and waist/height ratio), puberty staging and NMR metabolomic profiles from serum were assessed. Statistics included multivariate analysis (principal component analysis, PCA) and multiple linear regression models with false discovery rate adjustment.Results214 participants had metabolomic profiles analyzed, mean age 11.9years (SD3.1), mean BMI z-score 2.49 (SD +/- 0.24), 53% females. Unsupervised PCA identified no separable clusters of individuals. Positive associations included BMI z-score and phenylalanine, total body fat % and lipids in medium HDL, and waist circumference and tyrosine; negative associations included total body fat % and the ratio of docosahexaenoic acid/total fatty acids and histidine. Stratifying by sex and puberty, patterns of associations with BMI z-score in post-pubertal males included positive associations with lipid-, cholesterol- and triglyceride-content in VLDL lipoproteins; total fatty acids; total triglycerides; isoleucine, leucine and glycoprotein acetyls.Conclusion In a paediatric cohort with obesity, increased adiposity measures, especially in post-pubertal males, were associated with distinct patterns in metabolomic profiles.</p

Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk

Background Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). Methods Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed.Results Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p p p p p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures.Conclusions In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.</p

Modest decrease in severity of obesity in adolescence associates with low arterial stiffness

Background and aimsChildhood obesity is associated with cardiovascular risk factors (CVRF), subclinical cardiovascular phenotypes (carotid intima-media thickness, cIMT; pulse-wave velocity, PWV; and carotid elasticity), and adult cardiovascular disease (CVD) mortality. In youth with obesity (body mass index, BMI ≥95th centile), we investigated associations between changes in adiposity and CVRF in early adolescence and subclinical cardiovascular phenotypes in late adolescence.MethodsParticipants had adiposity measures (the severity of obesity in percentage >95th BMI-centile (%>95th BMI-centile)), waist circumference (WC), percentage total body fat (%BF) and CVRF (systolic blood pressure, SBP; glycoprotein acetyls, GlycA; and low-density lipoprotein cholesterol) assessed in early (mean age 10.2 ± 3.5y) and late (15.7 ± 3.7y) adolescence. Subclinical cardiovascular phenotypes were assessed in late adolescence. Multivariable regression analysis was performed.ResultsDecreasing the %>95th BMI-centile was associated with carotid elasticity (0.945%/10 mmHg, p = 0.002) in females, and with PWV in males (−0.75 m/s, p p p μmol-increase) were associated with elasticity (−0.162%/10 mmHg, p = 0.042), and changes in SBP (per 10 mmHg-increase) were associated with PWV (0.260 m/s, p μm, p = 0.006).ConclusionsIn youth with obesity, decreasing or maintaining the severity of obesity, and decreasing the levels of SBP and GlycA from early to late adolescence was associated with low arterial stiffness.</p

Evidence for Protein Leverage in Children and Adolescents with Obesity

Objective The aim of this study was to test the protein leverage hypothesis in a cohort of youth with obesity.Methods A retrospective study was conducted in a cohort of youth with obesity attending a tertiary weight management service. Validated food questionnaires revealed total energy intake (TEI) and percentage of energy intake from carbohydrates (ì), fats (ï), and proteins (%EP). Individuals with a Goldberg cutoff >= 1.2 of the ratio of reported TEI to basal metabolic rate from fat-free mass were included. A subgroup had accelerometer data. Statistics included modeling of percentage of energy from macronutrients and TEI, compositional data analysis to predict TEI from macronutrient ratios, and mixture models for sensitivity testing.Results A total of 137 of 203 participants were included (mean [SD] age 11.3 [2.7] years, 68 females, BMI z score 2.47 [0.27]). Mean TEI was 10,330 (2,728) kJ, mean ì was 50.6% (6.1%), mean ï was 31.6% (4.9%), and mean %EP was 18.4% (3.1%). The relationship between %EP and TEI followed a power function (L coefficient -0.48; P Conclusions In youth with obesity, protein dilution by either carbohydrates or fats increases TEI. Assessment of dietary protein may be useful to assist in reducing TEI and BMI in youth with obesity.</p

Environment versus genetics in the development of health-related problems in childhood obesity

© 2017 Dr. Kung-Ting KaoIntroduction: Childhood obesity is a major health concern affecting a quarter of all Australian youth. Obese youth are at risk of multi-systemic obesity-related comorbidities (ORC), such as Prediabetes and Type 2 Diabetes Mellitus (T2DM), Hypertension, Hyperlipidaemia, Non-alcoholic fatty liver disease (NAFLD), Polycystic ovarian syndrome (PCOS), Obstructive sleep apnoea (OSA), mental health and orthopaedic issues. However, within the obese population, the severity of obesity is a poor predictor of these comorbidities. As such, current guidelines advise screening obese youth for all comorbidities, which is both time consuming and costly. ORC, as with obesity itself, are complex polygenic disorders involving interaction between genetic and environmental risk factors. Furthermore, many of these interactions are likely mediated by epigenetic variation, linking environmental exposures with genetic predisposition. Therefore, clarification of the role of environmental exposures, genetic risk factors and epigenetic profile in obese youth may provide valuable insight into determining which obese youth are at risk of developing ORC. The aim of this study was to characterise and investigate the associations between environmental, genetic and epigenetic factors with obesity-related comorbidities in obese youth. This information obtained will allow clinicians to better predict and profile the comorbidity burden in obese youth for targeting interventions to those most likely to benefit. Materials and Methods: The Childhood Overweight BioRepository of Australia collected comprehensive clinical and anthropometric data, as well as blood samples for genetic, metabolic and hormonal profile testing from patients (age 1 to 18 years) attending the Weight Management Clinic at the Royal Children’s Hospital, Melbourne. Anthropometric measures included standard measurements of weight, height and waist circumference (converted into BMI z-score (BMI-Z) and waist-height ratio for analyses) as well as total percentage body fat (%FM) and percentage truncal body fat (%truncal) using bioimpedance. Dietary intake was assessed using the Australian Child and Adolescent Eating Survey and physical activity was measured objectively using accelerometry. Genetic typing and epigenetic profiling of single nucleotide polymorphisms (SNP) and measures of DNA methylation were performed using the SEQUENOM MassARRAY platform. Results: 349 participants were included in the study. Both metabolic and non-metabolic ORC are common in obese youth. The most commonly used measure of adiposity, BMI-Z, was the anthropometric marker least associated with ORC, while important ORCs such as T2DM and hyperlipidaemia were not significantly associated with any of the anthropometric measures. The presence of two or more significantly elevated anthropometric markers was associated with the presence of a higher number of ORCs. Almost all obese youth reported poor vegetable intake and high sedentary behaviour (TV-watching and total media) time. Although initial analyses observed associations between sedentary behaviour (TV-watching and total media use time) with prediabetes and hyperlipidaemia, unhealthy food options with mental health issues, and high fruit intake with NAFLD, these associations lost significance after correction for multiple testing by false discovery procedure (FDR). However, low vitamin D levels were significantly associated with hypertension, independent of adiposity and season. The Fat Mass and Obesity (FTO) gene has the largest influence on adiposity amongst obesity-risk genes to date and has been associated with ORCs. In our cohort, the FTO risk allele was associated with poorer longitudinal weight outcomes in pre-pubertal children, but not pubertal adolescents. The FTO SNP however was not associated with any ORCs. We also examined the association between the top 22 T2DM risk SNPs identified from previous studies and Prediabetes or T2DM status. The SLC30A8 rs13266634 SNP appeared to be protective of prediabetes/T2DM status in unadjusted analysis but lost significant on FDR testing. The addition of T2DM SNPs profile to TV-watching time improved the predictive model for Prediabetes/T2DM status. We were not able to replicate the previously reported association of FTO CpG hypomethylation with prediabetes/T2DM in obese children and adolescents. However FTO hypomethylation was seen in obese youth with NAFLD, independent of age, sex and total body adiposity. FTO methylation was independent of FTO expression, which was not associated with any ORC. Conclusion: Anthropometry is not associated with comorbidities in childhood obesity. Environmental factors do not appear to be associated with comorbidities. Low vitamin D level is associated with hypertension. Genetic factors impact on weight gain but not comorbidities, and epigenetic factors may contribute to NAFLD. Combining these environmental and genetic elements with established clinical risk factors in the assessment of each individual ORC may assist in enhancing current clinical models of care for obese children and adolescents

Staying at Work? The Impact of Social Support on the Perception of the COVID-19 Epidemic and the Mediated Moderating Effect of Career Resilience in Tourism

The COVID-19 epidemic has caused dramatic impacts and changes in the tourism industry, and job insecurity and emotional exhaustion have created psychological stress and negative emotions. Social support for Taiwan tourism workers (travel agency, transportation industry, lodging industry, tourism and leisure industry, etc.) plays an important role in their career resilience. However, not all of the potential social support moderators have a critical impact. This study used PLS-SEM analysis to survey 373 respondents by using an online questionnaire to investigate the critical influence of social support on the spread of COVID-19 using career motivation theory. In addition to the direct relationship between the individual’s psychological resilience and social support, the strategy of social support (family and friends, national relief policies and workplace support) is also pointed out. The results of the study illustrate the effectiveness of workplace support in combating the epidemic. This study provides information on effective resistance to the epidemic, how to prolong career resilience during unexpected shocks and stresses, and how to understand the mechanisms of adaptation or resilience in adversity and complements the study of factors and literature base in resilience research. It is also used as a study of the impact factors and industry strategy planning in future research

Staying at Work? The Impact of Social Support on the Perception of the COVID-19 Epidemic and the Mediated Moderating Effect of Career Resilience in Tourism

The COVID-19 epidemic has caused dramatic impacts and changes in the tourism industry, and job insecurity and emotional exhaustion have created psychological stress and negative emotions. Social support for Taiwan tourism workers (travel agency, transportation industry, lodging industry, tourism and leisure industry, etc.) plays an important role in their career resilience. However, not all of the potential social support moderators have a critical impact. This study used PLS-SEM analysis to survey 373 respondents by using an online questionnaire to investigate the critical influence of social support on the spread of COVID-19 using career motivation theory. In addition to the direct relationship between the individual&rsquo;s psychological resilience and social support, the strategy of social support (family and friends, national relief policies and workplace support) is also pointed out. The results of the study illustrate the effectiveness of workplace support in combating the epidemic. This study provides information on effective resistance to the epidemic, how to prolong career resilience during unexpected shocks and stresses, and how to understand the mechanisms of adaptation or resilience in adversity and complements the study of factors and literature base in resilience research. It is also used as a study of the impact factors and industry strategy planning in future research

Incidence trends of Diabetic Ketoacidosis in children and adolescents with Type 1 diabetes in British Columbia, Canada

Objectives: To estimate the 11-year incidence trend of diabetic ketoacidosis (DKA) at and after the diagnosis of type 1 diabetes.Study design: A retrospective cohort study using a population-based administrative cohort diagnosed with type 1 diabetes at &lt;20 years of age from 2002 to 2012 in British Columbia, Canada. DKA at (1 episode per individual) and DKA after (multiple episodes per individual) the diagnosis of diabetes were defined as DKA occurring ≤14 days or &gt;14 days, respectively, from diagnosis, identified using International Classification of Diseases, 9th and 10th editions codes. Incidence rate ratios were estimated using Poisson regression and DKA trends using Joinpoint regression analyses.Results: There were 1519 individuals (mean age at first-DKA, 12.6 ± 5.9 years; 50% male) with ≥1 DKA episode identified. Of 2615 incident cases of type 1 diabetes, there were 847 (32.4%; mean age, 9.9 ± 4.8 years; 52% male) episodes of DKA at the diagnosis of diabetes. Among prevalent cases of type 1 diabetes (1790 cases in 2002 increasing to 2264 in 2012), there were 1886 episodes of DKA after the diagnosis of diabetes (mean age at first DKA, 15.7 ± 5.2 years). The rates per 100 person-years of DKA at diabetes diagnosis (ranging from 24.1 in 2008 to 37.3 in 2006) and DKA after diabetes diagnosis (ranging from 4.9 in 2002 to 7.7 in 2008) remained stable. Females showed a 67% higher rate of incidence of DKA after the diagnosis of diabetes compared with their male counterparts (incidence rate ratio, 1.67; 95% CI, 1.50-1.86; P &lt; .001), adjusted for the temporal trend by fiscal year. Younger age at diagnosis (&lt;5 years) was associated with a greater risk of DKA at the time of diabetes diagnosis and older children (≥10 years) had a greater risk of DKA after the diagnosis of diabetes.Conclusions: The risk of DKA at the time of diagnosis of diabetes was greater with younger age and the risk of DKA after the diagnosis of diabetes was higher in females and older children and youth