Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children.

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.

Altered gait patterns during arch important development period in children with persistent obesity: An experimental longitudinal study.

BACKGROUND: Obesity can cause structural changes and functional adjustments in growing children's feet. However, there is a lack of continuous observation of changes in feet in children with persistent obesity during important developmental periods. This makes it challenging to provide precise preventive measures. OBJECTIVE: This study aimed to investigate the effects of persistent obesity on gait patterns in children at an important stage in the formation of a robust foot arch. METHODS: The Footscan® plantar pressure system was used for 3 checks over two years. A total of 372 children aged 7-8 years participated in the study, and gait data from 33 children who maintained normal weight and 26 children with persistent obesity were finally selected. Repeated measures ANOVA or Friedman's test were used for longitudinal comparisons. Independent-Sample t-tests or the Mann-Whitney-Wilcoxon tests were used for cross-sectional comparisons. RESULTS: During the important period of development, children with persistent obesity did not exhibit a significant decrease in the arch index and had significantly higher values than the normal group in the third check. The persistently obese children showed increased load accumulation in the lateral rearfoot, first metatarsophalangeal joints, and the great toe regions. Children with persistent obesity had significantly greater medial-lateral displacements in the initial contact phase and forefoot contact phase than normal children in the first check. These differences diminished between the second and third checks. SIGNIFICANCE: Persistent obesity during an important period of foot development leads to slow or abnormal development of arch structure and affects foot loading patterns with heel inverted and forefoot everted. Additionally, the development of gait stability is not limited by persistent obesity.

Effects of Functional Strength Training Combined with Aerobic Training on Body Composition, Physical Fitness, and Movement Quality in Obese Adolescents.

This study aimed to compare the effects of 12 weeks of functional strength training combined with aerobic training (TG) and traditional resistance training combined with aerobic training (CG) on the body composition, physical fitness, and movement quality of obese adolescents. Forty participants were randomly assigned to either the TG group (n = 20) or the CG group (n = 20). Each group underwent training five times per week, lasting 120 min each time, over a total period of 12 weeks. All participants followed a strict dietary program. Anthropometric parameters, body composition, physical fitness, and movement quality were evaluated at baseline and after intervention. A two-way repeated measures ANOVA observed a significant interaction between time and group for body mass (p = 0.043), body fat percentage (p = 0.045), body mass index (p = 0.025), neck circumference (p = 0.01), chest circumference (p = 0.027), left-hand grip strength (p = 0.043), right-hand grip strength (p = 0.048), standing broad jump (p = 0.044), and total Functional Movement Screen score (p = 0.003), and the improvement was greater for TG in comparison to CG. TG was found to be more effective than CG in enhancing body composition, physical fitness, and movement quality in obese adolescents.

Endocan: A biomarker for endothelial dysfunction and inflammation, linking maternal obesity and pediatric obesity in a cohort of preterm neonates.

OBJECTIVES: Numerous animal and epidemiologic studies have demonstrated a positive association between maternal obesity in pregnancy and obesity in offspring. The biologic mechanisms of this association remain under investigation. One proposed mechanism includes fetoplacental endothelial dysfunction secondary to inflammation. Endocan is a relatively new biomarker for endothelial dysfunction and inflammation. Our objectives were to examine (1) the association between maternal obesity and neonatal serum endocan at birth, and (2) the association between neonatal serum endocan at birth and pediatric obesity at 24-36 months of age. STUDY DESIGN: This was a secondary analysis of a prospective cohort of neonates born < 33 weeks gestation. Serum endocan was collected within 48 hours of birth. Serum endocan levels were compared in neonates born to obese mothers vs. those born to non-obese mothers. BMI data were retrospectively collected from cohort neonates between 24 and 36 months of age. RESULTS: The analysis included 120 mother/neonate dyads. Neonates born to obese mothers had higher median serum endocan at birth compared to neonates born to non-obese mothers (299 ng/L [205-586] vs. 251 ng/L [164-339], p = 0.045). In a linear regression modeled on neonatal serum endocan level, maternal obesity had a statistically significant positive association (p = 0.021). Higher mean serum endocan level at birth was associated with pediatric obesity between 24 and 36 months (obese vs. non-obese offspring; 574 ng/L (222) vs. 321 ng/L (166), p = 0.005). CONCLUSIONS: In our cohort of preterm neonates, elevated serum endocan at birth was associated with both maternal obesity and downstream pediatric obesity. More research is needed to understand intergenerational transmission of obesity. A large focus has been on epigenetic modification. Endothelial dysfunction and inflammation may play important roles in these pathways. Effective biomarkers, including endocan, may also serve as intermediate outcomes in future pregnancy research.

Examination of sensory reception and integration abilities in children with and without Prader-Willi syndrome.

BACKGROUND: Good postural stability control is dependent upon the complex integration of incoming sensory information (visual, somatosensory, vestibular) with neuromotor responses that are constructed in advance of a voluntary action or in response to an unexpected perturbation. AIMS: To examine whether differences exist in how sensory inputs are used to control standing balance in children with and without Prader-Willi syndrome (PWS). METHODS AND PROCEDURES: In this cross-sectional study, 18 children with PWS and 51 children categorized as obese but without PWS (without PWS) ages 8-11 completed the Sensory Organization Test®. This test measures the relative contributions of vision, somatosensory, and vestibular inputs to the control of standing balance. The composite equilibrium score (CES) derived from performance in all sensory conditions, in addition to equilibrium scores (EQs) and falls per condition were compared between groups. OUTCOMES AND RESULTS: The CES was lower for children with PWS compared to children without PWS (M=53.93, SD=14.56 vs. M=66.17, SD=9.89, p = .001) while EQs declined in both groups between conditions 1 and 4 (F (1.305, 66.577) = 71.381, p < .001). No group differences in the percent of falls were evident in condition 5 but more children with PWS fell in condition 6 (χ2 (1) = 7.468, p = .006). Group differences in frequency of repeated falls also approached significance in conditions 5 (χ2 (3) = 4.630, p = .099) and 6 (χ2 (3) = 5.167, p = .076). CONCLUSIONS AND IMPLICATIONS: Children with PWS demonstrated a lower overall level of postural control and increased sway when compared to children with obesity. Both the higher incidence and repeated nature of falls in children with PWS in conditions 5 and 6 suggest an inability to adapt to sensory conditions in which vestibular input must be prioritized. Postural control training programs in this population should include activities that improve their ability to appropriately weight sensory information in changing sensory environments, with a particular focus on the vestibular system. WHAT DOES THIS STUDY ADD?: This study shows that children with PWS demonstrate a lower level of postural stability. The results suggest that children with PWS show inability to adapt to sensory conditions that require prioritizing vestibular information to maintain postural control. This information can be used to help guide training programs in this population.

Association Between Elevated Body Mass Index and Cardiac Organ Damage in Children and Adolescents: Evidence and Mechanisms.

INTRODUCTION: Although a number of pathophysiological aspects of childhood obesity have been reported, few information are available on obesity-related cardiac organ damage. AIM: The present study was aimed at assessing the impact of anthropometric, blood pressure (BP) and metabolic variable on cardiac structure and function in youth. METHODS: In 78 subjects aged 5-16 years attending the outpatient clinic of cardiovascular risk (Valencia, Spain) anthropometric and metabolic variables, clinic and ambulatory BP and echocardiographic parameters were assessed. Subjects were also classified according to the presence of insulin resistance. RESULTS: Subjects mean age (± SD) amounted to 12.03 ± 2.4 years and males to 53.8%. Ten subjects were normoweight, 11 overweight, 39 obese, and 18 severely obese. No significant difference in office and ambulatory BP was detected among different bodyweight groups. A significant direct correlation was observed between left ventricular mass index (LVMI) and obesity markers [body mass index (BMI): r = 0.38, waist circumference (WC): r = 0.46, P < 0.04 for both]. Left ventricular hypertrophy, relative wall thickness and left atrial diameter were significantly related to BMI and WC. In contrast, office and ambulatory BP were unrelated to other variables, and differences in LVMI among different BP phenotypes were not significant. When partitioning the population by insulin resistance, LVMI, adjusted for confounders, was significantly greater in the insulin-resistant group. CONCLUSIONS: In children and adolescents characterized by different body weight patterns, weight factors "per se" and the related insulin resistance state appear to represent the main determinants of LVMI and left ventricular hypertrophy, independently on BP values and BP phenotypes.

Cardiorespiratory and Muscular Fitness in Children and Adolescents with Obesity.

PURPOSE OF REVIEW: Examine the current state of literature related to the impact of obesity in children and adolescents on health-related physical fitness and the resultant cardiometabolic disease risk. RECENT FINDINGS: Cardiorespiratory fitness of children and adolescents has declined over the past few decades which corresponds with an increase in obesity rates. Children with obesity are more likely to have low cardiorespiratory fitness which is associated with higher cardiometabolic disease risk and poorer mental health. The impact of obesity on muscular fitness in children and adolescents is more difficult to ascertain, but in general measures of physical function are lower in children with obesity which has also been associated with higher cardiometabolic disease risk. Components of health-related physical fitness are trending negatively in children and adolescents and appear to be related to the increase in prevalence of obesity. The resultant cardiometabolic disease risk has also risen which suggests a greater disease burden in the future. These disparaging findings highlight the need for aggressive interventions to improve physical fitness in children and adolescents.

The Effect of Childhood Obesity on Intraocular Pressure, Corneal Biomechanics, Retinal Nerve Fiber Layer, and Central Macular Thickness.

PRCIS: Elevated corneal hysteresis (CH) and resistance factor (CRF) in obese and overweight children imply weight's effect on corneal biomechanics. Increased Goldmann-correlated intraocular pressure (IOPg) in obese children indicates glaucoma risk, emphasizing screening for IOP and retinal changes. PURPOSE: To evaluate the effect of obesity on corneal biomechanics, retinal nerve fiber layer (RNFL), and central macular thickness (CMT) in children. PATIENTS AND METHODS: In this prospective, cross-sectional, comparative study, 146 eyes of normal-weight, over-weight, and obese children aged between 6 to 17 years were evaluated. The IOPg, corneal compensated IOP (IOPcc), CH, CRF, and the average retinal nerve fiber layer (RNFL), average cup-to-disk ratio (c/d), and central macular thickness (CMT) were measured by Ocular Response Analyser and Spectral-Domain Optical Coherence Tomography (SD-OCT), respectively. RESULTS: There was no statistically significant difference regarding age, gender, IOPcc, average RNFL thickness, c/d ratio, and CMT among the groups ( P ≥0.05). The IOPg was significantly higher in obese children compared with normal-weight children, while CH and CRF values were significantly higher in both obese and over-weight children compared with healthy ones ( P <0.05). There was a positive correlation between BMI percentile and IOPg, CH, and CRF values. CONCLUSION: In our study, higher IOPg, corneal hysteresis, and corneal resistance factor values suggest that obese children could be potential candidates for glaucoma. Therefore, it would be appropriate to screen them for IOP and retinal alterations. Further investigations with larger sample size and longer follow-up are needed to understand the risk of glaucoma in obese children.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

Insufficient Bone Mineralization to Sustain Mechanical Load of Weight in Obese Boys: A Cross-Sectional Study.

CONTEXT: The increase in bone mineral content (BMC) and density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in obese children may not sustain the mechanical load associated with weight, and the factors influencing bone mineralization are not well known. OBJECTIVE: We described bone mineralization in boys with overweight/obesity and leanness in relation to body composition. METHODS: Cross-sectional study in the Pediatric Endocrinology Unit of Angers University Hospital with 249 overweight/obese boys aged 8-18 who underwent DXA and insulin, testosterone, and IGF-1 measurements. Bone mineralization was compared with data from 301 lean boys of similar age and height from NHANES 2011-2015, using the same DXA model. Path analyses were performed to evaluate factors associated with total body less head (TBLH) BMC. RESULTS: The mean age- and height-adjusted difference in TBLH BMC between obese and lean boys was 241 ± 20 g/cm2. Each 1 kg/m2 increase in BMI was associated with +39 ± 6 g of TBLH BMC in lean subjects vs + 25 ± 3 g in obese subjects (P < .05). Each 1 kg/m2 increase in lean BMI (LBMI) was associated with +78 ± 5 g of TBLH BMC in lean and obese boys, and each 1 kg/m2 increase in fat mass index (FMI) was associated with a decrease of 9 ± 3 g of TBLH BMC. The TBLH BMC was directly positively influenced by LBMI and indirectly and positively influenced by IGF-1, testosterone, and insulin (mediated through height and LBMI). FMI indirectly influenced TBLH BMC, both positively through LBMI and negatively through its negative impact on IGF-1 and testosterone. CONCLUSION: The increase in bone mineralization in obese children does not adapt to the increase in body mass.

Reduced exercise capacity for muscle mass in adolescents living with obesity.

BACKGROUND: Adolescents living with obesity (AlwO) can have limited exercise capacity. Exercise capacity can be predicted by a 2-factor model comprising lung function and leg muscle function, but no study has looked at cycling leg muscle function and its contribution to cycling exercise capacity in AlwO. METHODS: Twenty-two nonobese adolescents and 22 AlwO (BMI > 95 percentile) were studied. Anthropometry, body composition (dual-energy X-ray absorptiometry), spirometry, 30-s isokinetic work capacity, and maximal exercise (cycle ergometry) were measured. RESULTS: AlwO had greater total body mass, lean body mass, and lean leg mass (LLM). Lung function trended higher in AlwO. Leg 30-s work did not differ in absolute terms or per allometrically scaled LLM. Peak oxygen consumption did not differ between the groups in absolute terms or as percent predicted values (79.59 ± 14.6 vs. 82.3 ± 11.2% predicted control versus ALwO) but was lower in AlwO when expressed per kg body mass, kg lean body mass, scaled lean body mass, and LLM. Peak oxygen consumption related to both lung function and 30-s work, with no observed group effect. 30-s leg work related to the scaled LLM, with a small group effect. There was some correlation between leg work and time spent in moderate to vigorous physical activity in AlwO (rs = 0.39, p = .07). CONCLUSION: AlwO have larger LLM and preserved exercise capacity, when expressed as percentage of predicted, but not per allometrically scaled LLM. Increasing time spent in moderate to vigorous activity may benefit AlwO.

Association between alanine aminotransferase as surrogate of fatty liver disease and physical activity and sedentary time in adolescents with obesity.

To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time. CONCLUSION: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. WHAT IS KNOWN: • MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. WHAT IS NEW: • Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.

Effect of Exercise Training on Arterial Stiffness in Overweight or Obese Populations.

The purpose was to analyze the effects of exercise training (ET) on arterial stiffness in all-age overweight or obese individuals. Sixty-one trials were included with ET improving flow-mediated dilation (FMD), pulse wave velocity (PWV), and intima-media thickness (IMT). In the subgroup analysis: (i) ET improved FMD in overweight or obese children and adolescents with a large effect size (SMD=0.83, 95% CI 0.42-1.25). PWV was decreased after ET regardless of age. IMT was decreased by ET in participants younger than 60, (ii) ET improved FMD, PWV, and IMT in participants whose BMI were smaller than 30 kg/m2, but ET only improved PWV of participants whose BMI were larger than 30 kg/m2. (iii) AE improved FMD, PWV, and IMT. High-intensity interval training (HIIT) decreased IMT. (iv) The increase of FMD only happened when training duration was longer than eight weeks. However, ET decreased PWV when the training duration was no longer than 12 weeks. IMT was decreased when the training duration was longer than eight weeks. ET instigated an improvement in endothelial function and arterial stiffness in overweight or obese populations, but depending on the different characteristics of exercise intervention and participants' demographics.

Predictors of Post-Exercise Energy Intake in Adolescents Ranging in Weight Status from Overweight to Severe Obesity.

Exercise may sensitize individuals with overweight and obesity to appetitive signals (e.g., hunger and fullness cues), overriding trait eating behaviors that contribute to overeating and obesity, such as uncontrolled eating. The objective of the current study was to measure predictors of objective ad libitum energy intake at a laboratory-based, post-exercise test-meal in adolescents ranging in weight status from overweight to severe obesity. We hypothesized that appetitive states, rather than appetitive traits, would be the strongest predictors of energy intake at a post-exercise test-meal, after controlling for body size. At Baseline, 30 adolescents (ages 10-16 years, 50% female (F), 43% non-Hispanic white (NHW), 83% with obesity (OB)) completed state and trait appetite measures and an ad libitum dinner meal following intensive exercise. Nineteen of those participants (47% F, 32% NHW, 79% OB) completed identical assessments two years later (Year 2). Energy intake (kcal) at each time point was adjusted for fat-free mass index (i.e., body size). Adjusted energy intake was reliable from Baseline to Year 2 (ICC = 0.84). Multiple pre-meal appetite ratings were associated with test-meal energy intake. In stepwise linear regression models, pre-meal prospective food consumption was the strongest and only significant predictor of test-meal energy intake at both Baseline (R2 = 0.25, p = 0.005) and Year 2 (R2 = 0.41, p = 0.003). Baseline post-exercise energy intake was associated with weight change over two years (R2 = 0.24, p = 0.04), but not with change in fat mass (p = 0.11). Appetitive traits were not associated with weight or body composition change (p > 0.22). State appetite cues were the strongest predictors of post-exercise energy intake, independent of body size. Future studies should examine whether long-term exercise programs enhance responsiveness to homeostatic appetite signals in youth with overweight and obesity, with a goal to reduce excess energy intake and risk for weight gain over time.

Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity.

Insulin resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from obese pre-diabetic Hispanic adolescents as indicators of abnormal metabolic regulation. Using the ReCIVA breathalyzer device for breath collection, we have identified a signature of 10 breath metabolites (breath-IR model), which correlates with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (R = 0.95, p < 0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R = 0.91, p < 0.001 and fasting glucose R = 0.80, p < 0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p = 0.003, p = 0.002, and p < 0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an AUC-ROC curve of 0.87, after cross-validation. Identification of a breath signature indicative of IR shows utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has potential as a diagnostic tool for monitoring IR progression, allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

Expression of the Adipocyte Progenitor Markers MSCA1 and CD36 is Associated With Adipose Tissue Function in Children.

CONTEXT: MSCA1 (mesenchymal stem cell antigen 1) and CD36 (cluster of differentiation 36) have been described as novel adipocyte progenitor markers in adults with a potential relevance for obesity and adipocyte progenitor function. OBJECTIVE: With the early manifestation of obesity in children and formation of adipose tissue (AT) dysfunction, children provide the opportunity to characterize the function of MSCA1 and CD36 during physiological AT accumulation and with obesity and related disease. METHODS: We investigated MSCA1 and CD36 expression in adipocytes and stroma vascular fraction (SVF) cells from 133 children of the Leipzig AT Childhood cohort with regard to AT accumulation and biology. In a subsample we analyzed how MSCA1 and CD36 expression is related to adipose progenitor capacities in vitro (ie, proliferation, differentiation and mitochondrial function). RESULTS: Both MSCA1 and CD36 are differentially expressed in adipocytes and SVF cells of children. MSCA1 expression is positively correlated to obesity-associated AT dysfunction (ie, adipocyte hypertrophy and serum high-sensitivity C-reactive protein), and high SVF MSCA1 expression is associated with increased mitochondrial respiration in vitro. CD36 expression is not associated with AT dysfunction but SVF CD36 expression is downregulated in children with overweight and obesity and shows a positive association with the differentiation capacity of SVF cells ex vivo and in vitro. CONCLUSION: Both MSCA1 and CD36 are associated with obesity-related alterations in AT of children. In particular, CD36 expression predicts adipogenic potential of SVF cells, indicating a potential role in the regulation of adipocyte hyperplasia and hypertrophy with obesity development in children.

Early life factors and white matter microstructure in children with overweight and obesity: The ActiveBrains project.

BACKGROUND & AIMS: Exposure to a suboptimal environment during the fetal and early infancy period's results in long-term consequences for brain morphology and function. We investigated the associations of early life factors such as anthropometric neonatal data (i.e., birth length, birth weight and birth head circumference) and breastfeeding practices (i.e., exclusive and any breastfeeding) with white matter (WM) microstructure, and ii) we tested whether WM tracts related to early life factors are associated with academic performance in children with overweight/obesity. METHODS: 96 overweight/obese children (10.03 ± 1.16 years; 38.7% girls) were included from the ActiveBrains Project. WM microstructure indicators used were fractional anisotropy (FA) and mean diffusivity (MD), derived from Diffusion Tensor Imaging. Academic performance was evaluated with the Battery III Woodcock-Muñoz Tests of Achievement. Regression models were used to examine the associations of the early life factors with tract-specific FA and MD, as well as its association with academic performance. RESULTS: Head circumference at birth was positively associated with FA of the inferior fronto-occipital fasciculus tract (0.441; p = 0.005), as well as negatively associated with MD of the cingulate gyrus part of cingulum (-0.470; p = 0.006), corticospinal (-0.457; p = 0.005) and superior thalamic radiation tract (-0.476; p = 0.001). Association of birth weight, birth length and exclusive breastfeeding with WM microstructure did not remain significant after false discovery rate correction. None tract related to birth head circumference was associated with academic performance (all p > 0.05). CONCLUSIONS: Our results highlighted the importance of the perinatal growth in WM microstructure later in life, although its possible academic implications remain inconclusive.

BMI metrics and their association with adiposity, cardiometabolic risk factors, and biomarkers in children and adolescents.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext.BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMIp95), percent of the BMI median (%BMIp50), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson's correlations. RESULTS: Data from 371 children and adolescents ages 8-21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190-0.768) than other BMI metrics. The %BMIp95 and %BMIp50 were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMIp95 and %BMIp50 were the most strongly correlated with measures of adiposity. %BMIp95 has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

Relation of glomerular filtration to insulin resistance and related risk factors in obese children.

BACKGROUND AND OBJECTIVE: Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes such as blood pressure and microalbuminuria. MATERIALS AND METHODS: We evaluated the relation of whole body insulin sensitivity and estimated glomerular filtration rate (eGFR) across the spectrum of obesity in children and adolescents. eGFR was calculated using the iCARE formula, which has been validated in obese children with varying glucose tolerance. RESULTS: 1080 children and adolescents with overweight and obesity (701 females and 379 males) participated. Insulin sensitivity was a strongly negatively associated with (B = -2.72, p < 0.001) eGFR), even after adjustment for potential confounders. Male sex emerged to be significantly associated with eGFR with boys having greater values than girls (B = 18.82, p < 0.001). Age was a positively associated (B = 2.86, p < 0.001) with eGFR. Whole body and hepatic insulin sensitivity decreased across eGFR quartiles. Adjusted eGFR was tightly positively associated with systolic blood pressure (B = 0.09, p = 0.003) and negatively associated with the presence of microalbuminuria (B = -2.18, p = 0.04). CONCLUSIONS: eGFR tends to increase with greater degrees of insulin resistance in children and adolescents representing hyperfiltration and is associated with cardiovascular risk factors. Longitudinal studies are needed to determine the natural history of childhood insulin resistance related hyperfiltration in regards to future kidney disease.