Citations

Introduction: Adolescent obesity is linked to significantly increased risk of cardiovascular and metabolic comorbidities. Exercise outcomes are often impaired in adolescents with obesity (AO), but it remains unclear whether this reflects compromised cardiovascular reserve or non-cardiovascular factors. This study aimed to characterize mechanisms of reduced exercise performance in AO using cardiopulmonary exercise testing (CPET). The secondary aim was to assess the contribution of excess weight burden by correcting for extra fat mass in AO through estimated standard body mass (eSBM). Methods: We retrospectively analyzed CPET data from asymptomatic AO, defined as BMI ≥ 30 (n = 94), and age-matched, normal-weight controls without obesity (n = 139). In a subset of AO (n = 47), % body fat was measured by bioelectric impedance analysis, and eSBM was calculated as if they have comparable % body fat to controls using median values by sex and age in US adolescents. CPET was performed with a cycle ergometer following a ramp protocol. Results: Both male and female AO exhibited higher resting HR (p < 0.001) while peak HR remained comparable to controls. Absolute peak oxygen consumption (VO2) was higher in female AO (p < 0.001), while males showed no difference. Absolute ventilatory anaerobic threshold (VAT) was elevated in AO in both sexes (p < 0.001). When indexed by total body weight, peak VO2, peak work rate (WR), and VAT were lower in both male and female AO (p < 0.001). Peak respiratory exchange ratio (RER), peak VO2/VAT, and peak WR/peak VO2 were also significantly reduced in AO (p < 0.001). When indexed by eSBM, peak VO2 normalized only in female AO; peak WR remained lower, but VAT normalized in AO of both sexes with overcorrection in females, suggesting comparable submaximal exercise performance to controls. Conclusion: Reduced exercise performance in AO appears characterized by elevated resting HR, early exhaustion near peak exercise (lower peak RER and peak VO2/VAT), and decreased work efficiency (lower peak WR/peak VO2). Indexing CPET parameters by eSBM revealed relatively normal cardiopulmonary performance in AO during submaximal exercise, suggesting that reduced performance primarily reflects premature, fatigue-driven termination of exercise due to excess weight burden rather than true cardiopulmonary compromise. Further study is needed to clarify factors contributing to the observed sex-specific differences in AO exercise performance.

Background Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among children in the United States (US), with severity and outcomes linked to social determinants of health (SDOH) and regional differences. Data on the impact of SDOH including race, sex, and Child Opportunity Index (COI) level on TBI severity in southeastern US are sparse in children. Methods We analyzed data retrospectively in 1063 children with TBI, admitted at a Level I Pediatric Trauma Center in the Southeast US between January 2017-June 2023. TBI severity was categorized using the Glasgow Coma Scale (GCS). Outcomes were length of hospital stay (LOHS), intensive care unit stay (LOICUS), and craniotomy frequency. Patients were classified by race ( white , Black , non-Black people of color [ NBPOC ]), COI (low, moderate, high), and sex (male, female). Statistical analyses included chi-square tests, one-way analysis of variance (ANOVA), and post-hoc comparisons. Results Significant disparities were observed by race and COI. Black children and children with low COI had lower GCS scores ( P < 0.01), longer LOHS and LOICUS ( P < 0.01) compared to white children and those with high COI. Additionally, Black and NBPOC children were more likely to undergo craniotomies than white children ( P < 0.05). No sex-based differences in TBI severity or outcomes were found. Discussion This study highlights the significant impact of SDOH, particularly race and COI, on pediatric TBI severity, surgical interventions, and outcomes. These findings underscore the need for targeted interventions to address health care disparities in vulnerable pediatric populations.

Abstract Background Prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction‐associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N ‐acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy‐confirmed MASLD. Methods Thirteen children ( n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double‐blind, placebo‐controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high‐sensitivity c‐reactive protein (hs‐CRP), and interleukin‐6 (IL‐6) were also measured. homeostasis model assessment for insulin resistance (HOMA‐IR) was calculated. Results Sixteen‐week NAC treatment improved (baseline adjusted between‐group p < .05 for all) markers of inflammation (IL‐6 and hs‐CRP), oxidative stress (GSH), and IR (HOMA‐IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. Conclusions Sixteen‐week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Abstract This mini-review aims to briefly summarize the pathophysiology of childhood obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) risk in children and adolescents. Recent data on efficacy of lifestyle interventions, medications, and metabolic surgery for obesity, T2DM, and CVD risk factors are also reviewed. We conducted a PubMed search of English-language original and review articles relevant to childhood obesity, T2DM, and CVD risk factors, and biomarkers in children with an emphasis on recent publications. Childhood obesity arises from an intricate interaction between genetic, physiologic, environmental, and socioeconomic factors. The rise in the prevalence of childhood obesity is associated with the development of comorbidities including T2DM and CVD at an early age. A multipronged approach is central to the detection, monitoring, and management of childhood obesity and associated adverse metabolic consequences.

Abstract Context Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. Objective We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). Methods Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. Results Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P &lt; 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P &lt; 0.05). The PAL-I produced only negligible effects (P &gt; 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P &lt; 0.05). Conclusion The novel finding of the BCAA–inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.

This study compared the effects of self-selected exercise intensity (SEI) versus predetermined exercise intensity (PEI) on blood pressure (BP) and arterial stiffness in adolescents with obesity. A total of 37 adolescents, 14.7 (1.6) years old, body mass index ≥95th percentile were randomly allocated into SEI (n = 18; 12 boys) or PEI (n = 19; 13 boys). Both groups exercised for 35 minutes on a treadmill, 3 times per week, for 12 weeks. The SEI could set the speed at the beginning of the sessions and make changes every 5 minutes. The PEI adolescents were trained at an intensity set at 60% to 70% of heart rate reserve. Brachial and central BP, pulse pressure, augmentation index, and carotid–femoral pulse wave were determined at baseline and after 12 weeks. Both groups reduced brachial systolic BP (SEI, Δ = −9 mm Hg; PEI, Δ = −4 mm Hg; P < .01), central systolic BP (SEI, Δ = −4 mm Hg; PEI, Δ = −4 mm Hg; P = .01), and central pulse pressure (SEI, Δ = −4 mm Hg; PEI, Δ = −3 mm Hg; P = .02) without differences between groups. No changes in the augmentation index and carotid–femoral pulse wave were observed in either group. The SEI induced similar changes in various cardiovascular outcomes compared with PEI in adolescents with obesity.

AbstractBackground and AimThis study aimed to evaluate the impact of physical activity (PA) on the course of hepatic steatosis (HS) in adults.MethodsHepatic steatosis status (ultrasonography) and PA levels were evaluated in 5860 subjects at baseline and after approximately 2.5 years (range: 19–50 months). At follow up, possible exposures to different PA levels were those who remained inactive, became inactive, became active, and remained active. After follow up, subjects were then classified according to the four possible states (outcomes): “remained without HS,” “developed HS” (subjects without HS at baseline), “remained with HS,” or “reverted HS.”ResultsAfter multivariate adjustments, individuals without HS that became or remained physically active were less likely to develop HS compared with those who remained physically inactive (odds ratio = 0.75, P = 0.04 and 0.75, P = 0.03, respectively). Among those with HS at baseline, becoming and remaining physically active beneficially improved the HS status (odds ratio = 0.64, P = 0.01 and 0.66, P = 0.01, respectively). However, the significance was lost when adjusted for changes in body mass index.ConclusionHigher levels of PA were associated with prevention and treatment of HS, with evidence of effect mediation by changes in body mass index.

Purpose: To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. Methods: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m−2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. Results: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL−1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL−1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL−1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL−1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL−1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. Conclusions: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.