Justin R. Ryder

Changes in inflammation, oxidative stress and adipokines following bariatric surgery among adolescents with severe obesity

Background/Objectives:Inflammation, oxidative stress and dysregulation of adipokines are thought to be pathophysiological mechanisms linking obesity to the development of insulin resistance and atherosclerosis. In adults, bariatric surgery reduces inflammation and oxidative stress, and beneficially changes the levels of several adipokines, but little is known about the postsurgical changes among adolescents.Subjects/Methods:In two separate longitudinal cohorts we evaluated change from baseline of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemo-attractant protein-1 (MCP-1), oxidized low-density lipoprotein cholesterol (oxLDL), adiponectin, leptin and resistin up to 12 months following elective laparoscopic Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) surgery in adolescents with severe obesity.Results:In cohort 1, which consisted of 39 adolescents (mean age 16.5±1.6 years; 29 females) undergoing either RYGB or VSG, IL-6 (baseline: 2.3±3.4 pg ml−1 vs 12 months: 0.8±0.6 pg ml−1, P<0.01), leptin (baseline: 178±224 ng ml−1 vs 12 months: 41.4±31.9 ng ml−1, P<0.001) and oxLDL (baseline: 41.6±11.6 U l−1 vs 12 months: 35.5±11.1 U l−1, P=0.001) significantly decreased and adiponectin significantly increased (baseline: 5.4±2.4 μg ml−1 vs 12 months: 13.5±8.9 μg ml−1, P<0.001). In cohort 2, which consisted of 13 adolescents (mean age 16.5±1.6 years; 10 females) undergoing RYGB, results were similar: IL-6 (baseline: 1.7±0.9 pg ml−1 vs 12 months: 0.4±0.9 pg ml−1, P<0.05) and leptin (baseline: 92.9±31.3 ng ml−1 vs 12 months: 37.3±33.4 ng ml−1, P<0.001) significantly decreased and adiponectin significantly increased (baseline: 6.1±2.9 μg ml−1 vs 12 months: 15.4±8.0 μg ml−1, P<0.001). When the cohorts were combined to evaluate changes at 12 months, oxLDL also significantly decreased (baseline: 39.8±16.7 U l−1 vs 12 months: 32.7±11.9 U l−1, P=0.03).Conclusions:Bariatric surgery produced robust improvements in markers of inflammation, oxidative stress and several adipokines among adolescents with severe obesity, suggesting potential reductions in risk for type 2 diabetes and cardiovascular disease.

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.

Effects of High-intensity Interval Training and Moderate-intensity Continuous Training on Endothelial Function and Cardiometabolic Risk Markers in Obese Adults

We hypothesized that high-intensity interval training (HIIT) would be more effective than moderate-intensity continuous training (MICT) at improving endothelial function and maximum oxygen uptake (V̇o2 max) in obese adults. Eighteen participants [35.1 ± 8.1 (SD) yr; body mass index = 36.0 ± 5.0 kg/m(2)] were randomized to 8 wk (3 sessions/wk) of either HIIT [10 × 1 min, 90-95% maximum heart rate (HRmax), 1-min active recovery] or MICT (30 min, 70-75% HRmax). Brachial artery flow-mediated dilation (FMD) increased after HIIT (5.13 ± 2.80% vs. 8.98 ± 2.86%, P = 0.02) but not after MICT (5.23 ± 2.82% vs. 3.05 ± 2.76%, P = 0.16). Resting artery diameter increased after MICT (3.68 ± 0.58 mm vs. 3.86 ± 0.58 mm, P = 0.02) but not after HIIT (4.04 ± 0.70 mm vs. 4.09 ± 0.70 mm; P = 0.63). There was a significant (P = 0.02) group × time interaction in low flow-mediated constriction (L-FMC) between MICT (0.63 ± 2.00% vs. -2.79 ± 3.20%; P = 0.03) and HIIT (-1.04 ± 4.09% vs. 1.74 ± 3.46%; P = 0.29). V̇o2 max increased (P < 0.01) similarly after HIIT (2.19 ± 0.65 l/min vs. 2.64 ± 0.88 l/min) and MICT (2.24 ± 0.48 l/min vs. 2.55 ± 0.61 l/min). Biomarkers of cardiovascular risk and endothelial function were unchanged. HIIT and MICT produced different vascular adaptations in obese adults, with HIIT improving FMD and MICT increasing resting artery diameter and enhancing L-FMC. HIIT required 27.5% less total exercise time and ∼25% less energy expenditure than MICT.

Changes in Functional Mobility and Musculoskeletal Pain After Bariatric Surgery in Teens With Severe Obesity: Teen–Longitudinal Assessment of Bariatric Surgery (LABS) Study

IMPORTANCE Severe obesity is associated with mobility limitations and higher incidence of multijoint musculoskeletal pain. It is unknown whether substantial weight loss improves these important outcomes in adolescents with severe obesity. OBJECTIVE To examine the association of bariatric surgery with functional mobility and musculoskeletal pain in adolescents with severe obesity up to 2 years after surgery. DESIGN, SETTING, AND PARTICIPANTS The Teen-Longitudinal Assessment of Bariatric Surgery Study is a prospective, multicenter, observational study, which enrolled 242 adolescents (≤19 years of age) who were undergoing bariatric surgery from March 2007 through February 2012 at 5 US adolescent bariatric surgery centers. This analysis was conducted in November 2015. INTERVENTIONS Roux-en-Y gastric bypass (n = 161), sleeve gastrectomy (n = 67), or laparoscopic adjustable gastric band (n = 14). MAIN OUTCOMES AND MEASURES Participants completed a 400-m walk test prior to bariatric surgery (n = 206) and at 6 months (n = 195), 12 months (n = 176), and 24 months (n = 149) after surgery. Time to completion, resting heart rate (HR), immediate posttest HR, and HR difference (resting HR minus posttest HR) were measured and musculoskeletal pain concerns, during and after the test, were documented. Data were adjusted for age, sex, race/ethnicity, baseline body mass index (calculated as weight in kilograms divided by height in meters squared), and surgical center (posttest HR and HR difference were further adjusted for changes in time to completion). RESULTS Of the 206 adolescents with severe obesity included in the study, 156 were female (75.7%), the mean (SD) age was 17.1 (1.6) years, and the mean (SD) body mass index was 51.7 (8.5). Compared with baseline, significant improvements were observed at 6 months for the walk test time to completion (mean, 376 seconds; 95% CI, 365-388 to 347 seconds; 95% CI, 340-358; P < .01), resting HR (mean, 84 beats per minute [bpm]; 95% CI, 82-86 to 74 bpm; 95% CI, 72-76), posttest HR (mean, 128 bpm; 95% CI, 125-131 to 113 bpm; 95% CI, 110-116), and HR difference (mean, 40 bpm; 95% CI, 36-42 to 34 bpm; 95% CI, 31-37). These changes in time to completion, resting HR, and HR difference persisted at 12 months and 24 months. Posttest HR further improved from 6 months to 12 months (mean, 113 bpm; 95% CI, 110-116 to 108 bpm; 95% CI, 105-111). There were statistically significant reductions in musculoskeletal pain concerns at all points. CONCLUSIONS AND RELEVANCE These data provide evidence that bariatric surgery in adolescents with severe obesity is associated with significant improvement in functional mobility and in the reduction of walking-related musculoskeletal pain up to 2 years after surgery.

Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study

Aims/hypothesisThe prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age.MethodsParticipants were from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were free from prediabetes/diabetes at baseline (year 0 [Y0]: 1985–1986). CRF was quantified by treadmill duration (converted to metabolic equivalents [METs]) at Y0, Y7 and Y20 and prediabetes/diabetes status was assessed at Y0, Y7, Y10, Y15, Y20 and Y25. We use an extended Cox model with CRF as the primary time-varying exposure. BMI was included as a time-varying covariate. The outcome was development of either prediabetes or diabetes after Y0. Model 1 included age, race, sex, field centre, CRF and BMI. Model 2 additionally included baseline (Y0) smoking, energy intake, alcohol intake, education, systolic BP, BP medication use and lipid profile.ResultsHigher fitness was associated with lower risk for developing incident prediabetes/diabetes (difference of 1 MET: HR 0.99898 [95% CI 0.99861, 0.99940], p < 0.01), which persisted (difference of 1 MET: HR 0.99872 [95% CI 0.99840, 0.99904], p < 0.01] when adjusting for covariates.Conclusions/interpretationExamining participants who had fitness measured from young adulthood to middle age, we found that fitness was associated with lower risk for developing prediabetes/diabetes, even when adjusting for BMI over this time period. These findings emphasise the importance of fitness in reducing the health burden of prediabetes and diabetes.

Exercise for Obese Youth: Refocusing Attention from Weight Loss to Health Gains

Despite evidence to the contrary, exercise interventions for obese youth target weight loss as a means of improving health. Using Exercise is Medicine® as a framework, we present a conceptual model for the beneficial effects of exercise independent of weight loss in obese youth and highlight novel biomarkers of cardiometabolic health that could prove useful as interventional targets for this population.

Lifestyle intervention improves lipoprotein particle size and distribution without weight loss in obese Latino adolescents.

Childhood obesity is associated with a pro‐atherogenic phenotype contributing to increased cardiovascular disease (CVD) risk. This single‐arm pilot study examined the effects of a lifestyle intervention on lipoprotein particle size and cholesterol distribution in obese Latino adolescents. Fifteen obese Latino adolescents (15.0 ± 1.0 years) completed a 12‐week nutrition education and exercise intervention. Low‐density lipoprotein (LDL) particle size and distribution of cholesterol in lipoprotein subclasses were determined via polyacrylamide gel electrophoresis. The intervention resulted in increases in mean LDL particle size (269.3 ± 3.4 to 271.6 ± 2.9 Å, P = 0.0003) and cholesterol in large high‐density lipoprotein (HDL) subfractions (22.4 ± 11.2 to 26.8 ± 10.6% area, P = 0.007) along with decreases of cholesterol in small LDL (1.6 ± 2.0 to 0.6 ± 1.2% area, P < 0.01) and HDL subfractions (23.2 ± 9.4 to 19.0 ± 6.7% area, P = 0.05). These improvements were observed independent of changes in weight (90.7 ± 26.2 to 89.9 ± 27.8 kg, P > 0.05) and suggest that lifestyle modification in obese youth may reduce cardiovascular risk by shifting lipoprotein particle size and cholesterol distribution to a less atherogenic phenotype.

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.

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.

Predictors of fat mass changes in response to aerobic exercise training in women

Abstract Sawyer, BJ, Bhammar, DM, Angadi, SS, Ryan, DM, Ryder, JR, Sussman, EJ, Bertmann, FMW, and Gaesser, GA. Predictors of fat mass changes in response to aerobic exercise training in women. J Strength Cond Res 29(2): 297–304, 2015—Aerobic exercise training in women typically results in minimal fat loss, with considerable individual variability. We hypothesized that women with higher baseline body fat would lose more body fat in response to exercise training and that early fat loss would predict final fat loss. Eighty-one sedentary premenopausal women (age: 30.7 ± 7.8 years; height: 164.5 ± 7.4 cm; weight: 68.2 ± 16.4 kg; fat percent: 38.1 ± 8.8) underwent dual-energy x-ray absorptiometry before and after 12 weeks of supervised treadmill walking 3 days per week for 30 minutes at 70% of . Overall, women did not lose body weight or fat mass. However, considerable individual variability was observed for changes in body weight (−11.7 to +4.8 kg) and fat mass (−11.8 to +3.7 kg). Fifty-five women were classified as compensators and, as a group, gained fat mass (25.6 ± 11.1 kg to 26.1 ± 11.3 kg; p < 0.001). The strongest correlates of change in body fat at 12 weeks were change in body weight (r = 0.52) and fat mass (r = 0.48) at 4 weeks. Stepwise regression analysis that included change in body weight and body fat at 4 weeks and submaximal exercise energy expenditure yielded a prediction model that explained 37% of the variance in fat mass change (R 2 = 0.37, p < 0.001). Change in body weight and fat mass at 4 weeks were moderate predictors of fat loss and may potentially be useful for identification of individuals who achieve less than expected weight loss or experience unintended fat gain in response to exercise training.