Exposure to 4,4'-DDE in visceral adipose tissue and weight loss in adolescents from the Teen-LABS cohort.

OBJECTIVE: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes. METHODS: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4'-DDE via fluorescent staining and imaging. RESULTS: A dose-response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4'-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation. CONCLUSIONS: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

BACKGROUND: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. METHODS: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. CONCLUSION: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

Opinions from the experts: Experiences of adolescents with severe obesity participating in meal replacement therapy.

BACKGROUND: Meal replacement therapy (MRT) is a structured treatment that is effective for short-term weight reduction in adolescents with severe obesity. However, like other interventions, MRT response is variable. OBJECTIVE: The goal of the current study was to characterize the experience of adolescents with severe obesity participating in MRT. METHODS: Seventeen adolescents with severe obesity participated in semi-structured, individual interviews about their experience participating in MRT. The authors used a biopsychosocial model as the theoretical framework and data was analysed using Interpretive Phenomenological Analysis. A biopsychosocial model views an individual's health as a blend of biological characteristics, behavioural factors, and social conditions. RESULTS: Results showed that adolescents with severe obesity described three biopsychosocial factors that were central to their experience with MRT: (1) scheduling and planning, (2) social support and pressure, and (3) intrapersonal factors. Specifically, adolescents with severe obesity identified that planning ahead, social support, and intrapersonal changes (e.g. self-confidence) can promote engagement in MRT. On the other hand, unplanned schedule changes, social pressures, and different intrapersonal factors (e.g., taste preference) can make engagement challenging. CONCLUSIONS: Adolescents provided information on factors that supported or hindered their engagement in MRT, and themes were consistent with prior literature on health behaviour change. Overall, adolescents would recommend MRT to other teenagers who carry extra weight. Future research can use the rich information provided by adolescents with severe obesity to enhance and individualize treatment options.

Relationship of Endothelial Microparticles to Obesity and Cardiovascular Disease Risk in Children and Adolescents.

Background Microparticles and endothelial microparticles (EMPs) are implicated in accelerating cardiovascular disease (CVD); however, data in pediatrics are limited. We examined the relationship of microparticles and EMPs with adiposity and subclinical CVD risk measures in a pediatric population to determine their potential as biomarkers of CVD risk. Methods and Results A cross-sectional study of youth (n=280; ages 8-20 years) with a range of body mass index categories was used. Microparticles, EMPs, and activated EMPs were measured by flow cytometry. %Body fat and %visceral adipose tissue were measured by dual X-ray absorptiometry. Measures of arterial stiffness and vascular wall structure were obtained. Linear regression (with log-transformed outcomes) and logistic regression were used to evaluate associations and all results were exponentiated. Youth with overweight/obesity and severe obesity had 2.50 (95% CI, 1.56-4.01) and 3.42 (95% CI, 2.15-5.43) times the geometric means of the total number of microparticles, respectively, compared with those with normal weight. Youth with overweight/obesity and severe obesity had 1.97 (95% CI, 1.09-3.55) and 2.34 (95% CI, 1.31-4.19) times the geometric means of the total number of EMPs, respectively, compared with those with normal weight. There were positive associations between the levels of both microparticles and EMPs with higher adiposity measures and poor CVD risk measures. Youth with higher adiposity showed 1.84 times the odds of having high levels of activated EMPs (%) (odds ratio, 1.84; 95% CI, 1.08-3.14) compared with those with normal weight. Conclusions Levels of microparticles, EMPs, and activated EMPs were positively associated with adiposity and poor subclinical CVD risk in a pediatric population.

Maternal obesity and acute lymphoblastic leukemia risk in offspring: A summary of trends, epidemiological evidence, and possible biological mechanisms.

Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented.

Comparison of automatic liver volumetry performance using different types of magnetic resonance images.

Measurements of liver volume from MR images can be valuable for both clinical and research applications. Automated methods using convolutional neural networks have been used successfully for this using a variety of different MR image types as input. In this work, we sought to determine which types of magnetic resonance images give the best performance when used to train convolutional neural networks for liver segmentation and volumetry. Abdominal MRI scans were performed at 3 Tesla on 42 adolescents with obesity. Scans included Dixon imaging (giving water, fat, and T2* images) and low-resolution T2-weighted scout images. Multiple convolutional neural network models using a 3D U-Net architecture were trained with different input images. Whole-liver manual segmentations were used for reference. Segmentation performance was measured using the Dice similarity coefficient (DSC) and 95% Hausdorff distance. Liver volume accuracy was evaluated using bias, precision, intraclass correlation coefficient, normalized root mean square error (NRMSE), and Bland-Altman analyses. The models trained using both water and fat images performed best, giving DSC = 0.94 and NRMSE = 4.2%. Models trained without the water image as input all performed worse, including in participants with elevated liver fat. Models using the T2-weighted scout images underperformed the Dixon-based models, but provided acceptable performance (DSC ≥ 0.92, NMRSE ≤6.6%) for use in longitudinal pediatric obesity interventions. The model using Dixon water and fat images as input gave the best performance, with results comparable to inter-reader variability and state-of-the-art methods.

Exenatide for weight-loss maintenance in adolescents with severe obesity: A randomized, placebo-controlled trial.

OBJECTIVE: This study sought to evaluate the effect of 52 weeks of exenatide extended release (XR) on the maintenance of meal replacement therapy (MRT)-induced BMI reduction in adolescents with severe obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, 100 participants aged 12 to 18 years with BMI ≥ 1.2 × 95th percentile were enrolled in a short-term MRT run-in phase. Those who achieved ≥5% BMI reduction during the run-in were then randomized to 52 weeks of exenatide XR 2.0 mg or placebo weekly. Both groups also received lifestyle therapy. The prespecified primary end point was mean percent change in BMI from randomization (post run-in) to 52 weeks in the intention-to-treat population. RESULTS: A total of 100 participants were enrolled, and 66 (mean age 16 = [SD 1.5] years; 47% female) achieved ≥5% BMI reduction with MRT and were randomized (33 to exenatide XR and 33 to placebo). From randomization (post run-in) to 52 weeks, mean BMI increased 4.6% and 10.1% in the exenatide XR and placebo groups, respectively. The placebo-subtracted exenatide XR treatment effect was -4.1% (95% CI: -8.6% to 0.5%, p = 0.078). CONCLUSIONS: Although not achieving statistical significance, exenatide XR, compared with placebo, may partly mitigate the propensity toward BMI rebound in adolescents who achieved initial weight loss with dietary intervention.

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.

Contribution of Hedonic Hunger and Binge Eating to Childhood Obesity.

Background: Studies examining the association between hedonic hunger, that is, having frequent thoughts about food in the absence of an energy deficit, and obesity in youth show mixed results. This may be due to the confounding effect of binge eating, which has been associated with both hedonic hunger and obesity. The purpose of this study was to determine the extent to which hedonic hunger is associated with obesity independent of binge eating in youth. Methods: Data for this cross-sectional study were collected from youth enrolled in a larger study of cardiovascular disease and obesity. Linear regression models were used to assess the association between hedonic hunger measured by Power of Food Scale (PFS) and binge eating measured by Eating Disorder Examination-Questionnaire, on percent of the 95th BMI percentile (BMIp95). Results: Among 269 participants (mean age 12.8 years), 16.4% endorsed binge eating. PFS was positively associated with BMIp95 with a difference in percent of BMIp95 of 5.9% [95% confidence interval (1.5-10.3), p = 0.009]. However, when binge eating was added to the model, the relationship between PFS and BMIp95 was no longer significant. Conclusion: Hedonic hunger, above and beyond binge eating, may not be associated with BMI. Future research should examine whether screening for and targeting binge eating rather than hedonic hunger in weight management care may have more impact on obesity outcomes. Clinical Trial Registration number: NCT01508598.

Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D. OBJECTIVE: To compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D. SETTING: Longitudinal multicenter studies at University hospitals. METHODS: A secondary analysis of data collected from the participants with T2D enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 30) and participants of similar age and racial distribution from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY, n = 63) studies was performed. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome, assessed at baseline (preoperatively for Teen-LABS), 1 year, and 5 years of follow-up. RESULTS: Participants with T2D from Teen-LABS (n = 30; mean ± SD age = 16.9 ± 1.3 yr; 70% female; 60% white; body mass index (BMI) = 54.4 ± 9.5 kg/m2) and TODAY (n = 63; 15.3 ± 1.3 yr; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m2) were compared. The likelihood of CVD events was higher in Teen-LABS versus TODAY at baseline (17.66 [1.59] versus 12.11 [.79]%, adjusted P = .002). One year after MBS, event risk was significantly lower in Teen-LABS versus TODAY (6.79 [1.33] versus 13.64 [0.96]%, adjusted P < .0001), and sustained at 5 years follow-up (adjusted P < .0001). CONCLUSION: Despite higher pretreatment risk for CVD events, treatment with MBS resulted in a reduction in estimated CVD event risks, whereas medical therapy associated with an increase in risk among adolescents with T2D and severe obesity.

Relationship of Circulating Endothelial Cells With Obesity and Cardiometabolic Risk Factors in Children and Adolescents.

Background Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8-20 years) were classified into normal weight (body mass index [BMI] percentage <85th; n=114), obesity (BMI percentage ≥95th to <120% of the 95th; n=63), and severe obesity (BMI percentage ≥120% of the 95th; n=94) catagories. CEC enumeration was determined using immunohistochemical examination of buffy coat smears and activated CEC (percentage of vascular cell adhesion molecule-1 expression) was assessed using immunofluorescent staining. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C-reactive protein, leptin, adiponectin, oxidized low-density lipoprotein cholesterol, carotid artery intima-media thickness, and pulse wave velocity. Linear regression models examined associations between CEC number and activation with BMI and cardiovascular risk factors. CEC number did not differ among BMI classes (P>0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1-15.6 [P=0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00-0.03 [P=0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00-0.01 [P=0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4-10.9 [P=0.034]) and non-high-density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01-0.21 [P=0.039]). Conclusions Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

Relationship of Apolipoproteins with Subclinical Cardiovascular Risk in Youth.

OBJECTIVE: To examine the association of apolipoproteins with arterial stiffness and carotid artery structure in children and adolescents. STUDY DESIGN: A total of 338 children and adolescents (178 female) with a mean age 13.0 ± 2.8 years were examined. Apolipoproteins (AI, AII, B100, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel. Applanation tonometry determined pulse wave velocity and ultrasound imaging measured carotid intima-media thickness. Dual X-ray absorptiometry measured total body fat percent. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for body fat percent. Linear regression models also examined the interaction between Tanner stage and apolipoproteins. RESULTS: There was a significant positive association between pulse wave velocity and apolipoproteins: AI (0.015 m/s/10 µg/mL [CI 0.005-0.026], P = .003), AII (0.036 m/s/10 µg/mL [0.017-0.056], P < .001), B100 (0.009 m/s/10 µg/mL [0.002-0.016], P = .012), E (0.158 m/s/10 µg/mL [0.080-0.235], P < .001), and CIII:CII (0.033/µg/mL [0.014-0.052], P < .001). After we added body fat percent to the models, pulse wave velocity (PWV) remained positively associated with greater levels of apolipoproteins: AI, AII, B100, E, and CIII:CII. Both with and without the adjustment for body fat percent, there were no significant associations between any apolipoprotein and carotid intima-media thickness. There were no significant interactions between Tanner stage and apolipoproteins. CONCLUSIONS: These findings suggest that greater levels of apolipoprotein AII, E, and CIII:CII are associated with increased arterial stiffness in children and adolescents, both with and without adjusting for percent body fat. These specific apolipoproteins may be useful as biomarkers of cardiovascular risk.

Body mass index associated with childhood and adolescent high-risk B-cell acute lymphoblastic leukemia risk: A Children's Oncology Group report.

BACKGROUND: Obesity is a risk factor for many adulthood cancers, but its role in childhood, adolescent, and young adult (AYA) cancer is unknown. Childhood and AYA acute lymphoblastic leukemia (ALL) incidence and obesity prevalence have shown concurrent increases. We sought to identify whether obesity may be a risk factor for childhood and AYA ALL. METHODS: Characteristics from individuals with ALL, aged 2-30 years, diagnosed 2004-2017 and treated on Children's Oncology Group (COG) protocols with available pre-treatment anthropometric data (N = 4726) were compared to National Health and Nutrition Examination Survey controls (COG AALL17D2). Body mass index (BMI) was defined using standard CDC definitions. Multivariate conditional logistic regression assessed associations between BMI and ALL with additional analyses stratified by sex and race/ethnicity. RESULTS: Among cases (72% high-risk (HR) B-ALL, 28% T-ALL), 5% had underweight, 58% normal weight, 17% overweight, and 20% obesity. Underweight (OR 2.11, 95% CI 1.56-2.85) and obesity (OR 1.32, 95% CI 1.15-1.53) were associated with B-ALL diagnosis. Specifically, obesity was associated with B-ALL among males (OR 1.57, 95% CI 1.30-1.91) and Hispanic children (OR 1.78, 95% CI 1.39-2.29). Obesity was also associated with central nervous system (CNS) involvement. CONCLUSION: Pre-treatment obesity is associated with HR B-ALL among males and Hispanics, as well as with CNS involvement, suggesting common physiology between obesity and leukemogenesis. An association between underweight and ALL was confirmed, likely due to cancer-associated wasting. These results have important public health implications for obesity prevention and treatment in children and adolescents to reduce cancer risk.

Accelerated Early Vascular Aging Among Adolescents With Obesity and/or Type 2 Diabetes Mellitus.

Background The normal rate of subclinical vascular aging from adolescence to young adulthood has not been well-characterized. We conducted a 5-year longitudinal study among adolescents with normal-weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging. Methods and Results Adolescents (mean [SD] age 17.6 [3.5]; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima-media thickness [cIMT]; common, internal, and bulb) and arterial stiffness (carotid-femoral pulse wave velocity, and augmentation index). Longitudinal (5-year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm [0.03, 0.06]; P<0.001), bulb cIMT (0.02 mm [0.00, 0.05]; P=0.033), internal cIMT (0.03 mm [0.01, 0.05]; P<0.001), and pulse wave velocity carotid-femoral (0.38 m/sec [0.14, 0.61]; P=0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm [0.04, 0.07]; P<0.001), bulb cIMT (0.06 mm [0.04, 0.09]; P<0.001), internal cIMT (0.04 mm [0.02, 0.07]; P<0.001), augmentation index (4.67% [2.20, 7.13]; P<0.001), and pulse wave velocity carotid-femoral (0.74 m/sec [0.46, 1.02]; P<0.001). Higher baseline systolic blood pressure was associated with greater positive change in common cIMT (0.007 mm [0.003, 0.011]; P<0.001), bulb cIMT (0.009 mm [0.002, 0.016]; P=0.01), internal cIMT (0.008 mm [0.003, 0.013]; P=0.001), and pulse wave velocity carotid-femoral (0.066 m/sec [0.002, 0.130]; P=0.042). Conclusions These longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.

Thirty-Year Risk of Cardiovascular Disease Events in Adolescents with Severe Obesity.

OBJECTIVE: Quantifying risk for cardiovascular disease (CVD) events among adolescents is difficult owing to the long latent period between risk factor development and disease outcomes. This study examined the 30-year CVD event risk among adolescents with severe obesity treated with and without metabolic and bariatric surgery (MBS), compared with youths with moderate obesity, overweight, or normal weight. METHODS: Cross-sectional and longitudinal comparisons of five frequency-matched (age and diabetes status) groups were performed: normal weight (n = 247), overweight (n = 54), obesity (n = 131), severe obesity without MBS (n = 302), and severe obesity undergoing MBS (n = 215). A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome. Data are mean (SD) with differences between time points for MBS examined using linear mixed models. RESULTS: Preoperatively, the likelihood of CVD events was higher among adolescents undergoing MBS (7.9% [6.7%]) compared with adolescents with severe obesity not referred for MBS (5.5% [4.0%]), obesity (3.9% [3.0%]), overweight (3.1% [2.4%]), and normal weight (1.8% [0.8%]; all P < 0.001). At 1 year after MBS, event risk was significantly reduced (7.9% [6.7%] to 4.0% [3.4%], P < 0.0001) and was sustained for up to 5 years after MBS (P < 0.0001, all years vs. baseline). CONCLUSIONS: Adolescents with severe obesity are at elevated risk for future CVD events. Following MBS, the predicted risk of CVD events was substantially and sustainably reduced.