Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays.

BACKGROUND: Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. METHODS: To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. RESULTS: Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals' metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. CONCLUSIONS: Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Application of Bioelectrical Impedance Analysis in Weight Management of Children with Spina Bifida.

BACKGROUND: Children with spina bifida (SB) face an elevated risk of obesity, which necessitates precise methods for assessing body composition to ensure effective weight management. Conventional measures like BMI are inadequate for this population because of variations in growth patterns and skeletal structure. Bioelectrical impedance analysis (BIA) is a method that offers a clearer picture of body composition, yet its use in children with SB remains underexplored. METHODS: Conducted on 57 children with SB and 28 healthy controls, with a median age of 11 years, this study evaluated anthropometrics, including BMI and BIA-derived metrics. The Hoffer's scale to assess physical activity was applied in SB children. RESULTS: Results showed that while 32% of SB patients were classified as overweight or obese based on BMI, 62% exhibited high body fat percentage via BIA. Fat-free mass, muscle and fat mass, and fat-to-muscle ratio (FMR) differed significantly compared to the reference group. Non-ambulators showed a higher median body fat mass percentage (25.9% vs. 17.8%, p = 0.01) and FMR (0.92 vs. 0.44, p = 0.003) in comparison to the community walkers. CONCLUSIONS: In SB children, BIA-measured fat mass is a better obesity indicator than BMI. Non-ambulatory, SB patients with obesity had the highest FMR values, indicating a higher risk for metabolic syndrome.

Clarifying main nutritional aspects and resting energy expenditure in children with Smith-Magenis syndrome.

Our study aims to define resting energy expenditure (REE) and describe the main nutritional patterns in a single-center cohort of children with Smith-Magenis syndrome (SMS). REE was calculated using indirect calorimetry. Patients' metabolic status was assessed by comparing measured REE (mREE) with predictive REE (pREE). Patients also underwent multidisciplinary evaluation, anthropometric measurements and an assessment of average energy intake, using a 3-day food diary, which was reviewed by a specialized dietitian. Twenty-four patients (13 M) were included, the median age was 9 years (IC 95%, 6-14 years), 84% had 17p11.2 deletion, and 16% had RAI1 variants. REE was not reduced in SMS pediatric patients, and the mREE did not differ from the pREE. In patients with RAI1 variants (16%, n = 3/24), obesity was more prevalent than those with 17p11.2 deletion (100% vs 38%). Lower proteins intake and higher total energy intake were reported in obese and overweight patients, compared to healthy weight children. No significant difference was found between males and females in energy or macronutrient intake. CONCLUSIONS: In SMS, the onset of obesity is not explained by REE abnormalities, but dietary factors seem to be crucial. Greater concern should be addressed to patients with RAI1 variants. A better understanding of the molecular mechanisms causing obesity in SMS patients could set the basis for possible future targeted therapies. WHAT IS KNOWN: • More than 90% of SMS patients after the age of 10 are overweight or obese. WHAT IS NEW: • Onset of overweight and obesity in SMS pediatric patients is not explained by abnormal resting energy expenditure. • The development of syndrome-specific dietary guidelines for SMS patients should be of utmost relevance and are highly needed.

Correlation between gross motor coordination and basic coordination capacities in normal-weight and overweight/obese children aged 9-10 years.

Background: Gross motor coordination (GMC) plays a crucial factor in children's motor development and daily activities. It encompasses various sub-capacities, such as spatial orientation, rhythm, and motor reaction, collectively referred to as basic coordination capacities (BCC). However, children who are overweight and obese (OW/OB) often display poorer GMC. This study aims to examine the impact of gender and weight status (BMI categories) on children's GMC and BCC. It also seeks to investigate the impact of BCC and BMI on GMC. Method: The study involved 266 participants, 135 in the NW group (boys: n = 75; girls: n = 60) and 131 in the OW/OB group (boys: n = 68; girls: n = 63). An NW status is defined by a BMI z-score between ≥-2SD to ≤1SD, while an OW/OB status corresponds to a BMI z-score > 1SD. Physical activity was assessed using the Physical Activity Questionnaire for Children, developed by the University of Saskatchewan, Canada. We used six field tests to evaluate BCC, including single leg standing test (static balance), YBT (dynamic balance), rhythmic sprint test (rhythm), reaction time test (motor reaction), target standing broad test (kinesthetic differentiation), and numbered medicine ball running test (spatial orientation). GMC was evaluated with Kiphard-Schilling's Body Coordination Test (KTK). Result: The motor quotient (MQ) was primarily affected by weight status (F = 516.599, p < 0.001; gender: F = 6.694, p = 0.01), with no significant interaction effect (F = 0.062, p = 0.803). In BCC, gender had a significant main effect on rhythm capacity (F = 29.611, p < 0.001) and static balance (F = 11.257, p = 0.001) but did not significant influence other sub-capacities (p > 0.05). Weight status impacted dynamic balance (F = 11.164, p = 0.001). The interaction of gender and weight status significantly impacted motor reaction (F = 1.471, p = 0.024) and kinesthetic differentiation (F = 5.454, p = 0.02), but did not affect other sub-capacities (p > 0.05). The physical activity was not significant affected by gender (F = 0.099, p = 0.753), weight status (F = 0.171, p = 0.679) and the interactions of two variables (F = 0.06, p = 0.806). In the regression analysis, except motor reaction (p > 0.05), other BCC sub-capacities influenced GMC to varying extents (ß = -0.103-0.189, p < 0.05). Nonetheless, only two types of balance significantly mediated the relationship between BMI and GMC (BMI→MQ: ß = -0.543, p < 0.001; BMI→YBT: ß = -0.315, p < 0.001; BMI→SLS: ß = -0.282, p < 0.001; SLS→MQ: ß = 0.189, p < 0.001; YBT→MQ: ß = 0.182, p < 0.001). Conclusion: Compared to gender, the main effect of weight status on most GMC and BCC's sub-capacities was more pronounced. OW/OB children exhibited poorer GMC, which is related to their reduced static and dynamic balance due to excess weight. Kinesthetic differentiation, spatial orientation, and rhythm capacity are not significantly associated with BMI, but these sub-capacities positively influence gross motor coordination (GMC), except for hand-eye motor reaction.

Metabolically healthy obesity and left ventricular geometric remodelling in Chinese children.

AIM: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children. MATERIALS AND METHODS: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling. RESULTS: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling. CONCLUSIONS: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children.

Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study.

Pediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated comorbidities. The construction of effective and robust predictive systems for a complex health outcome like insulin resistance during the early stages of life demands the adoption of longitudinal designs for more causal inferences, and the integration of factors of varying nature involved in its onset. In this work, we propose an eXplainable Artificial Intelligence-based decision support pipeline for early diagnosis of insulin resistance in a longitudinal cohort of 90 children. For that, we leverage multi-omics (genomics and epigenomics) and clinical data from the pre-pubertal stage. Different data layers combinations, pre-processing techniques (missing values, feature selection, class imbalance, etc.), algorithms, training procedures were considered following good practices for Machine Learning. SHapley Additive exPlanations were provided for specialists to understand both the decision-making mechanisms of the system and the impact of the features on each automatic decision, an essential issue in high-risk areas such as this one where system decisions may affect people's lives. The system showed a relevant predictive ability (AUC and G-mean of 0.92). A deep exploration, both at the global and the local level, revealed promising biomarkers of insulin resistance in our population, highlighting classical markers, such as Body Mass Index z-score or leptin/adiponectin ratio, and novel ones such as methylation patterns of relevant genes, such as HDAC4, PTPRN2, MATN2, RASGRF1 and EBF1. Our findings highlight the importance of integrating multi-omics data and following eXplainable Artificial Intelligence trends when building decision support systems.

Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.

BACKGROUND: Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. METHODS: The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. RESULTS: Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. CONCLUSIONS: Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.

Abnormal blood pressure and pediatric obesity phenotype: Red flags for clinical practice.

BACKGROUND AND AIMS: systolic and diastolic blood pressure values identify different subtypes of Primary Hypertension. In pediatric age, hypertension is often related to obesity. Characterization of an individual's Blood Pressure (BP) status needs multiple measurements in the course of time, but this is rarely the case, principally in everyday pediatrics. Thus, the finding of abnormal BP values even in a single routine check visit should need a special attention. The aim of this study was to evaluate if even a single abnormal measurement could be a marker of metabolic risk, according to clinical and/or metabolic phenotype and subtypes of hypertension in a population of overweight/obese children and adolescents. METHODS AND RESULTS: We reviewed data from 489 overweight-obese children and adolescents. BP values were classified according to American Academy of Pediatrics Guidelines (2017). Considering study design, we used the term "Abnormal" instead of "High" BP. Data on lipid profile, glucose metabolism and ultrasonographic pattern of the liver were recorded. Mean age was 9.4 ± 2.5 years: 76.9% had normal BP values. Children with Abnormal BP harbored more frequently an unfavorable metabolic profile. Children with Abnormal Systolic-Diastolic BP values had higher BMI z-score and Waist to Height ratio (p = 0.022 and p = 0.032). Hepatic Steatosis was detected in 4.5%, 14.8 % and 17.6 % of children with normal, abnormal systolic and abnormal systo-diastolic blood pressure, respectively. (p < 0.001). CONCLUSION: Identification of abnormal BP subtypes even in a single measurement could be useful for identification of specific clinical-metabolic phenotypes allowing an individual targeted management of obesity-related comorbidities.

The evaluation of kidney function estimation during lifestyle intervention in children with overweight and obesity.

BACKGROUND: Children with overweight and obesity are at risk for developing chronic kidney disease (CKD). During lifestyle adjustment, the first step in the treatment of childhood obesity, body proportions are likely to change. The aim of this study was to examine how lifestyle intervention affects creatinine-based kidney function estimation in children with overweight and obesity. METHODS: This longitudinal lifestyle intervention study included 614 children with overweight and obesity (mean age 12.17 ± 3.28 years, 53.6% female, mean BMI z-score 3.32 ± 0.75). Loss to follow-up was present: 305, 146, 70, 26, and 10 children were included after 1, 2, 3, 4, and 5 (about yearly) follow-up visits, respectively. Serum creatinine (SCr) was rescaled using Q-age and Q-height polynomials. RESULTS: At baseline, 95-97% of the children had a SCr/Q-height and SCr/Q-age in the normal reference range [0.67-1.33]. SCr/Q significantly increased each (about yearly) follow-up visit, and linear mixed regression analyses demonstrated slopes between 0.01 and 0.04 (corresponding with eGFR FAS reduction of 1.1-4.1 mL/min/1.73 m2) per visit. BMI z-score reduced in both sexes and this reduction was significantly higher in males. No correlation between change in rescaled SCr and BMI z-score reduction could be demonstrated. CONCLUSIONS: Rescaled serum creatinine (SCr/Q) slightly increases during multidiscipline lifestyle intervention in this cohort of children with overweight and obesity. This effect seems to be independent from change in BMI z-score. Whether this minor decrease in estimated kidney function has clinical consequences in the long term remains to be seen in trials with a longer follow-up period. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov; Registration Number: NCT02091544.

Physiological response during exercise is preserved in children exposed to a suboptimal gestational environment.

OBJECTIVE: This study investigated whether exposure to suboptimal gestational factors (SGFs) alters mechanical efficiency (ME) and substrate oxidation during rest and exercise in children as a mechanism contributing to obesity. METHODS: Data from the Quebec Adiposity and Lifestyle Investigation in Youth cohort were used. Children aged 8 to 10 years performed an incremental maximal cycling test with indirect calorimetry. Their ME was measured during submaximal and maximal effort. The substrate oxidation during rest and submaximal effort was also computed. ME and substrate oxidation results between children exposed to each SGF during pregnancy (gestational diabetes mellitus: n = 68; hypertensive disorders: n = 49; maternal smoking: n = 77) and nonexposed children (n = 370) were compared. RESULTS: No difference was observed for ME during submaximal (F[3,540] = 0.46, p = 0.713) and maximal effort (F[3,545] = 0.86, p = 0.463) between exposed and nonexposed children. The percentage contributions of lipids and carbohydrates did not differ during rest (F[3,545] =1.68, p = 0.169) or submaximal exercise (F[3,544] = 0.31, p = 0.534) between exposed and nonexposed children. CONCLUSIONS: Children exposed to investigated SGFs display a similar physiological response regarding ME and substrate oxidation during rest and exercise compared to nonexposed children. Future studies should confirm these novel results and continue investigating other research avenues to explain the higher risk of obesity in this population.

Childhood obesity's effect on cognition and brain connectivity worsens with low family income.

Childhood obesity and its adverse health consequences have risen worldwide, with low socioeconomic status increasing the risk in high-income countries like the United States. Understanding the interplay between childhood obesity, cognition, socioeconomic factors, and the brain is crucial for prevention and treatment. Using data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated how body mass index (BMI) relates to brain structural and functional connectivity metrics. Children with obesity or who are overweight (n = 2,356) were more likely to live in poverty and exhibited lower cognitive performance compared with children with a healthy weight (n = 4,754). Higher BMI was associated with multiple brain measures that were strongest for lower longitudinal diffusivity in corpus callosum; increased activity in cerebellum, insula, and somatomotor cortex; and decreased functional connectivity in multimodal brain areas, with effects more pronounced among children from low-income families. Notably, nearly 80% of the association of low income and 70% of the association of impaired cognition on BMI were mediated by higher brain activity in somatomotor areas. Increased resting activity in somatomotor areas and decreased structural and functional connectivity likely contribute to the higher risk of being overweight or having obesity among children from low-income families. Supporting low-income families and implementing educational interventions to improve cognition may promote healthy brain function and reduce the risk of obesity.

The assessment of adolescent obesity's effects on ventricular repolarization.

BACKGROUND: Currently, there is a lack of research on the Tp-Te interval and Tp-e/QT ratio in obese adolescents who have metabolic syndrome. AIM: Our study aims to compare established ventricular repolarization parameters with these intervals and ratios in obese adolescents with or without metabolic syndrome, alongside a healthy control group, while exploring the association of these repolarization parameters with cardiovascular risk factors and echocardiographic variables. METHODS: The study included 100 obese adolescents and 50 lean subjects, with the obese participants categorized into two subgroups. The Tp-Te interval was identified as the duration from the peak to the end of the T wave. RESULTS: The metabolic and non-metabolic syndrome obese groups exhibited significantly elevated QTc and TpTe values compared to the control group, with no statistically significant differences observed in minimum QT, maximum QT, QT dispersion, QTc dispersion, TpTe dispersion, and TpTe/QT ratio values among obese subjects with metabolic or non-metabolic syndrome and controls. Specifically, TpTe values were significantly elevated in the non-metabolic syndrome obese groups compared to controls, while minimum TpTe values were significantly elevated in the metabolic syndrome obese groups compared to controls, and the prolongation of the QTc interval was notably elevated in the obese groups than in controls. CONCLUSIONS: Obese adolescents demonstrated an elevated TpTe interval compared to healthy controls, without any significant differences observed in TpTe dispersion, and TpTe/QT ratio values between the two groups. Results of our study showed that a negative correlation between TpTe and HDL-cholesterol and a positive correlation between the TpTe/QT ratio and insulin sensitivity indices in adolescents with metabolic syndrome.

The association between parental cardiovascular health status and the risk of obesity in their offspring: Tehran Lipid and Glucose Study.

BACKGROUND AND AIMS: Little is known about the association of parental cardiovascular risk factors with the risk of obesity in offspring. We aimed to investigate whether parental ideal cardiovascular health (ICVH) status was associated with the risk of general and central obesity in their young/adult offspring. METHODS AND RESULTS: Of individuals who participated in the 2012-15 phase of the Tehran Lipid and Glucose Study, 2395 pairs of parent-unmarried offspring aged ≥6 years were selected in this cross-sectional study. General and central obesity were defined based on Iranian BMI percentile reference data for offspring aged ≤18 years. For subjects aged ≥19 years, central obesity was defined based on the introduced cut-off points for Iranian adults. We employed the American Heart Association's 2020 impact goal criteria of ICVH. The mean ± SD age of fathers and mothers were respectively 55.4 ± 9.79 and 48.4 ± 9.88. About 55% of offspring were older than 19 years. Higher adherence to ICVH score in mothers was associated with lower risk of overweight/obesity in female offspring (OR for Q1-Q4: 1, 0.56, 0.57, 0.37, P < 0.05 for all quartiles). Among ICVH components, only ideal BMI status in fathers was observed to be associated with a lower risk of overweight/obesity in their male offspring. The risk of abdominal obesity decreased in female offspring with increasing total ICVH score in mothers. CONCLUSION: Higher adherence of parents to ICVH and its components was positively associated with a lower risk of general and abdominal obesity in their offspring. Our findings demonstrate that maternal-offspring relationship was stronger than paternal-offspring association.

High muscular fitness level may positively affect bone strength and body composition in children with overweight and obesity.

Muscular fitness plays a major role in bone health and body composition in overweight and obese children. It is key that the development of this muscle fitness is affected by absolute isometric strength and dynamic strength. PURPOSE: To compare bone health and body composition between overweight/obese children considering muscular fitness (MF) levels, and to investigate whether weight-bearing dynamic or absolute isometric strength, both involved in the development of this muscular fitness, are more related with bone health. METHODS: MF of 59 overweight or obese children (10.1 ± 0.9 years, 27 females) was measured by a countermovement jump (CMJ), handgrip, and maximal isometric strength of knee extension. Participants were divided into four groups depending on their MF level performing a cluster analysis: 16 children with high MF (HMF) in all tests, 18 with high performance in isometric strength (HIS), 15 with high performance in CMJ (HCMJ) and 10 low isometric and low dynamic force values (LMF). Body composition values were measured by dual energy X-ray absorptiometry, and bone strength values were assessed by peripheral quantitative computed tomography. Motor skills were evaluated using TGMD-3. Multivariate analysis of covariance test was applied to analyse bone strength differences between children in the different MF groups, using maturity offset, height and weight as covariates, and correlations were investigated. RESULTS: HMF excelled in bone health. HIS had higher cortical bone area, periosteal circumference, bone mass, polar strength strain index and fracture load than LMF, while HCMJ only showed better results in trabecular bone area than LMF. HMF had significantly better values of fracture load and periosteal and endosteal circumferences than HCMJ, but not than HIS. CONCLUSIONS: High MF level shows positive effects on bone health in overweight/obese children. Those with highest isometric strength had better bone health compared to those with higher dynamic strength. TRIAL REGISTRATION: The research project was registered in a public database Clinicaltrials.gov in June 2020 with the identification number NCT04418713.

Kidney function evaluation in children and adolescents with obesity: a not-negligible need.

The role of obesity as risk factor for chronic kidney disease (CKD) has been well-recognized. As previously demonstrated in adults, emerging data highlighted the relevant impact of obesity on renal function since childhood. As a matter of fact, obesity also affects renal health through a complex pathogenic mechanism in which insulin resistance (IR) plays a pivotal role. Worthy of note, the vicious interplay among obesity, IR, and renal hemodynamics clinically translates into a plethora of kidney function impairments potentially leading to CKD development. Therefore, renal injury needs to be added to the well-known spectrum of cardiometabolic obesity comorbidities (e.g., type 2 diabetes, IR, metabolic syndrome, cardiovascular disease). CONCLUSION: Taking this into account, a careful and timely monitoring of kidney function should not be neglected in the global assessment of children with obesity. We aimed to provide a comprehensive overview on the relevance of kidney evaluation in children with obesity by shedding lights on the intriguing relationship of obesity with renal health in this at-risk population. WHAT IS KNOWN: • Obesity has been found to be a risk factor for chronic kidney disease. • Unlike adults, pediatric data supporting the association between obesity and renal function are still limited. WHAT IS NEW: • As observed in adults, obesity might affect renal function since childhood. • Kidney function should be carefully evaluated in children with obesity.

Dietary content and combined training, but not daily physical activity, are associated with 6-month bone mineral changes in adolescents with obesity: A Secondary analysis of the PAC-MAnO trial.

PURPOSE: The present study aimed to explore the influence of diet and physical activity (PA) changes on bone mineral content (BMC) and density (BMD) alterations in adolescents with obesity undergoing a weight loss program. METHODS: Six-month longitudinal data from 71 adolescents (aged 15.1 [± 1.6] years; 57.7% girls) with a BMI z-score of 3.03 (± 0.78), previously recruited for the PAC-MAnO trial, were analyzed using Generalized Estimation Equations for over time changes and linear regressions with BMC, BMD and BMD z-score as dependent variables, adjusting for confounders (including type of exercise- aerobic vs. combined). RESULTS: Adjusting for confounders, changes in carbohydrate (CH) and protein content showed to positively and negatively predict BMD z-score variance, respectively (ß = 0.44, 95%CI: 0.01, 0.04, p < .001); ß = -0.57, 95%CI: -0.06, -0.03, p < .001), yet no associations were found between PA and bone-related parameters. Combined exercise showed better results on BMC compared to aerobic exercise (ß = 0.09, 95%CI: 0.05 to 0.13, p < .001). CONCLUSIONS: Increased CH content, instead of protein, may be associated with BMD improvements in adolescents with obesity. Type of exercise may moderate the impact of PA on bone health. TRIAL REGISTRATION: Clinicaltrials.gov NCT02941770. What is Known • Adolescents with obesity may be at a higher risk of osteopenia/osteoporosis • Obesity and inadequate diet and physical activity (PA) may have an adverse effect on bone metabolism What is New • Improvements in adiposity and muscle mass and increased diet carbohydrate content are associated with bone mineral density (BMD) improvements • Type of exercise (i.e., combined training vs. aerobic) may moderate the impact of PA on BMD, and calcium intake may mediate this impact.

Early Life Surgency, but not Effortful Control or Negative Affectivity, Is a Mediating Variable Between Maternal Pre-Pregnancy Body Mass Index and Childhood Obesity Risk.

Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted ß = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted ß = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.

Children with obesity have poorer circadian health as assessed by a global circadian health score.

BACKGROUND: Circadian health refers to individuals' well-being and balance in terms of their circadian rhythm. It is influenced by external cues. In adults, a close relationship between circadian-related alterations and obesity has been described. However, studies in children are scarce, and circadian health and its association with obesity have not been evaluated globally. We aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score (GCS) in a school-age population. METHODS: Four hundred and thirty-two children (7-12 years) were recruited in Spain. Non-invasive tools were used to calculate the GCS: (1) 7-day rhythm of wrist temperature (T), activity (A), position (P), an integrative variable that combines T, A, and P (TAP); (2) cortisol; and (3) 7-day food and sleep records. Body mass index, body fat percentage, waist circumference (WC), melatonin concentration, and cardiometabolic marker levels were determined. RESULTS: Circadian health, as assessed by the GCS, differed among children with obesity, overweight, and normal weight, with poorer circadian health among children with obesity. Children with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health, respectively, than did those with normal weight or low WC. The percentage of rhythmicity, a marker of the robustness of the TAP rhythm, and the amplitude, both components of the GCS, decreased with increasing obesity. Different lifestyle behaviors were involved in the association between circadian health and obesity, particularly protein intake (P = 0.024), physical activity level (P = 0.076) and chronotype (P = 0.029). CONCLUSIONS: The GCS can capture the relationship between circadian health and obesity in school-age children. Protein intake, physical activity level, and chronotype were involved in this association. Early intervention based on improving circadian health may help to prevent childhood obesity.

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.