Claudia K. Fox

Physical Activity and Sports Team Participation: Associations with Academic Outcomes in Middle School and High School Students.

BACKGROUND Previous studies have found that higher physical activity levels are associated with greater academic achievement among students. However, it remains unclear whether associations are due to the physical activity itself or sports team participation, which may involve requirements for maintaining certain grades, for example. The purpose of this study is to examine the associations between sports team participation, physical activity, and academic outcomes in middle and high school students. METHODS Data were drawn from Project EAT (Eating Among Teens), a survey of middle and high school students (n = 4746). Students self-reported their weekly hours of physical activity, sports team participation, and academic letter grades. Two statistical models were considered: first, 2 separate regression analyses with grade point average (GPA) as the outcome and either sports team participation or physical activity as the predictor; second, a single regression with GPA as the outcome and both sports team participation and physical activity as the simultaneous predictors. RESULTS For high school girls, both physical activity and sports team participation were each independently associated with a higher GPA. For high school boys, only sports team participation was independently associated with a higher GPA. For middle school students, the positive association between physical activity and GPA could not be separated from the relationship between sports team participation and a higher GPA. CONCLUSIONS Regardless of whether academic success was related to the physical activity itself or to participation on sports teams, findings indicated positive associations between physical activity involvement and academic achievement among students.

The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity: a randomized, placebo-controlled, clinical trial.

IMPORTANCE Medical treatment options for pediatric obesity remain limited. Glucagon-like peptide-1 (GLP-1) receptor agonists induce weight loss by suppressing appetite and increasing satiety, but few studies have evaluated this therapy as a treatment for obesity. OBJECTIVE To evaluate the effects of exenatide on body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and cardiometabolic risk factors in adolescents with severe obesity. DESIGN Three-month, randomized, double-blind, placebo-controlled, multicenter clinical trial followed by a 3-month open-label extension. SETTING An academic medical center and an outpatient pediatric endocrinology clinic. PATIENTS A total of 26 adolescents (12-19 years of age) with severe obesity (BMI ≥ 1.2 times the 95th percentile or BMI ≥ 35). INTERVENTION All patients received lifestyle modification counseling and were equally randomized to exenatide or placebo injection, twice per day. MAIN OUTCOME MEASURES The primary end point was the mean percent change in BMI measured at baseline and 3 months. Secondary end points included absolute change in BMI, body weight, body fat, blood pressure, hemoglobin A1c, fasting glucose, fasting insulin, and lipids at 3 months. RESULTS Twenty-two patients completed the trial. Exenatide elicited a greater reduction in percent change in BMI compared with placebo (-2.70% [95% CI, -5.02% to -0.37%]; P = .03). Similar findings were observed for absolute change in BMI (-1.13 [95% CI, -2.03 to -0.24]; P = .02) and body weight (-3.26 kg [95% CI, -5.87 to -0.66 kg]; P = .02). Although not reaching the level of statistical significance, reduction in systolic blood pressure was observed with exenatide. During the open-label extension, BMI was further reduced in those initially randomized to exenatide (cumulative BMI reduction of 4%). CONCLUSIONS AND RELEVANCE These results provide preliminary evidence supporting the feasibility, safety, and efficacy of GLP-1 receptor agonist therapy for the treatment of severe obesity in adolescents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01237197.

Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study.

The objective of this pilot study was to evaluate the effects of exenatide on BMI (primary endpoint) and cardiometabolic risk factors in nondiabetic youth with extreme obesity. Twelve children and adolescents (age 9–16 years old) with extreme obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2) were enrolled in a 6‐month, randomized, open‐label, crossover, clinical trial consisting of two, 3‐month phases: (i) a control phase of lifestyle modification and (ii) a drug phase of lifestyle modification plus exenatide. Participants were equally randomized to phase‐order (i.e., starting with control or drug therapy) then crossed‐over to the other treatment. BMI, body fat percentage, blood pressure, lipids, oral glucose tolerance tests (OGTT), adipokines, plasma biomarkers of endothelial activation, and endothelial function were assessed at baseline, 3‐, and 6‐months. The mean change over each 3‐month phase was compared between treatments. Compared to control, exenatide significantly reduced BMI (−1.7 kg/m2, 95% confidence interval (CI) (−3.0, −0.4), P = 0.01), body weight (−3.9 kg, 95% CI (−7.11, −0.69), P = 0.02), and fasting insulin (−7.5 mU/l, 95% CI (−13.71, −1.37), P = 0.02). Significant improvements were observed for OGTT‐derived insulin sensitivity (P = 0.02) and β‐cell function (P = 0.03). Compliance with the injection regimen was excellent (≥94%) and exenatide was generally well‐tolerated (the most common adverse event was mild nausea in 36%). These preliminary data suggest that exenatide should be evaluated in larger, well‐controlled trials for its ability to reduce BMI and improve cardiometabolic risk factors in youth with extreme obesity.

Hyperleptinemia and hypoadiponectinemia in extreme pediatric obesity.

BACKGROUND Adiponectin and leptin, adipokines associated with metabolic syndrome, type 2 diabetes, and cardiovascular disease, have not been well characterized in extreme pediatric obesity. Therefore, levels were compared in youth that were extremely obese (EO) to normal weight (NW), overweight (OW), and obese (OB) youth. METHODS Leptin, adiponectin, body mass index (BMI), blood pressure, fasting glucose, insulin, and lipids were obtained in 277 children and adolescents (age 13.4±2.6 years; 152 boys). Participants were classified into four BMI groups (NW, OW, OB, EO). Variables were compared across groups using analysis of covariance (ANCOVA) adjusted for gender, age, and race. RESULTS Risk factors generally worsened across BMI groups. EO had significantly higher levels of leptin than OB (P<0.0001), OW (P<0.0001), and NW (P<0.0001). Leptin was higher in OB compared to OW (P<0.005) and NW (P<0.0001) and higher in OW compared to NW (P<0.0001). Adiponectin levels in EO did not significantly differ from OB or OW but were significantly lower than NW (P<0.0001). Adiponectin was not significantly different among the OB, OW, and NW groups. CONCLUSIONS Leptin was markedly elevated in EO children and adolescents, suggesting that this subset of obese youth may be at particularly high risk of future weight gain and potentially reduced response to weight-loss interventions.

Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations

Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity.

Postprandial endothelial function, inflammation, and oxidative stress in obese children and adolescents

Most studies in adults suggest that acute glucose consumption induces a transient impairment in endothelial function. We hypothesized that obese youth would demonstrate reduced endothelial function and increased inflammation and oxidative stress following acute glucose ingestion and that transient elevations in plasma glucose would correlate with endothelial dysfunction, inflammation, and oxidative stress. Thirty‐four obese (BMI ≥95th percentile) children and adolescents (age 12.4 ± 2.6 years; BMI = 37.9 ± 6.7 kg/m2; 50% females) underwent measurement of endothelial function (reactive hyperemic index (RHI)), glucose, insulin, C‐reactive protein (CRP), interleukin‐6 (IL‐6), circulating oxidized low‐density lipoprotein (oxLDL), and myeloperoxidase (MPO) in a fasting state and at 1‐ and 2‐h following glucose ingestion. Repeated measures ANOVA with Tukey post‐tests and Pearson correlations were performed. Glucose and insulin levels significantly increased at 1‐ and 2‐h (all P values < 0.001). Compared to baseline, there were no statistically significant differences in 1‐ and 2‐h RHI, CRP, IL‐6, and oxLDL. However, MPO significantly decreased at the 1‐ (P < 0.05) and 2‐h (P < 0.001) time points. At the 1‐h time point, glucose level was significantly inversely correlated with RHI (r = −0.40, P < 0.05) and at the 2‐h time point, glucose level was positively correlated with MPO (r = 0.40, P < 0.05). An acute oral glucose load does not reduce endothelial function or increase levels of inflammation or oxidative stress in obese youth. However, associations of postprandial hyperglycemia with endothelial function and oxidative stress may have implications for individuals with impaired glucose tolerance or frank type 2 diabetes.

Topiramate for Weight Reduction in Adolescents With Severe Obesity

Background. Medications for use as an adjunct to lifestyle modification therapy (LSM) for severe adolescent obesity are limited. Topiramate results in weight reduction in adults with obesity, but has not been studied in adolescents. Objective. To examine the effect of topiramate plus LSM on body mass index (BMI) reduction in adolescents with severe obesity. Methods. Data for this retrospective chart review were collected from patients attending a pediatric weight management program who were treated with LSM plus topiramate for 3 months minimum. Mean BMI percent change from baseline was evaluated using t-tests. Results. Twenty-eight patients (mean age 15.2 ± 2.5 years, mean baseline BMI 46.2 ± 10.3 kg/m2) were identified for inclusion. The 6-month percent change in BMI was −4.9, 95% confidence interval (−7.1, −2.8), P < .001. Conclusions. Topiramate with concurrent LSM was associated with clinically meaningful BMI reduction in adolescents with severe obesity. Randomized controlled clinical trials examining efficacy and safety of topiramate for severe obesity in adolescents are needed.

Impaired cardiac autonomic nervous system function is associated with pediatric hypertension independent of adiposity.

Background:We examined whether sympathetic nervous system activity influences hypertension status and systolic blood pressure (SBP) independent of adiposity in youth ranging from normal-weight to severe obesity.Methods:We examined the association of heart rate variability (HRV) with hypertension status and SBP among youth (6–18 y old; n = 188; 103 female). Seated SBP was measured using an automated cuff. Prehypertension (SBP percentile ≥ 90th to <95th) and hypertension (SBP percentile ≥ 95th) were defined by age-, sex-, and height-norms. Autonomic nervous system activity was measured using HRV via SphygmoCor MM3 system and analyzed for time- and frequency-domains. Total body fat was measured via dual-energy X-ray absorptiometry.Results:Logistic regression models demonstrated lower values in each time-domain HRV measure and larger low-frequency (LF):high-frequency (HF) ratio to be significantly associated with higher odds of being prehypertensive/hypertensive (11–47% higher odds) independent of total body fat (P < 0.05). In linear regression analysis, lower time-domain, but not frequency-domain, HRV measures were significantly associated with higher SBP independent of total body fat (P < 0.05).Conclusion:These data suggest that impaired cardiac autonomic nervous system function, at rest, is associated with higher odds of being prehypertensive/hypertensive and higher SBP which may be independent of adiposity in youth.

Depression, Anxiety, and Severity of Obesity in Adolescents: Is Emotional Eating the Link?

The purposes of this study were to characterize the impact of depression and anxiety on the severity of obesity among youth seeking weight management treatment and to determine the extent to which emotional eating mediates the relationship between depression and/or anxiety and degree of obesity. This cross-sectional, retrospective chart review of 102 adolescent patients from a weight management clinic analyzed demographics, body mass index, depression (Patient Health Questionnaire-9), and anxiety (Generalized Anxiety Disorder Scale-7) screens and the Child Eating Behavior Questionnaire, Emotional Over-Eating subscale. After adjusting for demographics and emotional eating, the odds of having severe obesity versus obesity were 3.5 times higher for patients with depression compared with those without (odds ratio [OR] = 3.5; 95% CI = 1.1, 11.3; P = .038) and nearly 5 times higher for those with anxiety (OR = 4.9; CI = 1.2, 20.9; P = .030). Emotional eating, however, was not a mediator between depression/anxiety and degree of adiposity.

Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial.

To assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.