Cardiometabolic risk factors in treatment-seeking youth versus population youth with obesity.

BACKGROUND: Although obesity affects approximately one in five youths, only a fraction is treated in pediatric weight management clinics. Characteristics distinguishing youth with obesity who seek weight management treatment from those who do not are largely unknown. Yet identification of specific health characteristics which differentiate treatment-seeking from non-treatment seeking youth with obesity may shed light on underlying motivations for pursuing treatment. OBJECTIVES: Compare the cardiometabolic profiles of an obesity treatment-seeking sample of youth to a population-based sample of youth with obesity, while controlling for body mass index (BMI). METHODS: This cross-sectional study included participants, ages 12-17 years, with obesity from the Pediatric Obesity and Weight Evaluation Registry (POWER) and National Health and Nutrition Examination Survey, representing the treatment-seeking and population samples, respectively. Mean differences were calculated for systolic and diastolic blood pressure percentiles, total cholesterol, low-density and high-density lipoprotein-cholesterol, triglycerides, fasting glucose, glycated hemoglobin and alanine aminotransferase, while adjusting for age, sex, race/ethnicity, insurance status, and multiple of the 95th BMI percentile. RESULTS: The POWER and National Health and Nutrition Examination Survey cohorts included 1,823 and 617 participants, respectively. The POWER cohort had higher systolic blood pressure percentile (mean difference 17.4, 95% confidence interval [14.6, 20.1], p < 0.001), diastolic blood pressure percentile (21.8 [19, 24.5], p < 0.001), triglycerides (42.3 [28, 56.5], p < 0.001) and alanine aminotransferase (7.5 [5.1, 9.8], p < 0.001) and lower fasting glucose (-6.9 [-8.2, -5.6], p < 0.001) and high-density lipoprotein-cholesterol (-2.3 [-3.8, -0.9], p < 0.002). There were no differences in total cholesterol or low-density lipoprotein-cholesterol or clinical differences in glycated hemoglobin. CONCLUSION: For a given BMI, obesity treatment-seeking youth are more adversely affected by cardiometabolic risk factors than the general population of youth with obesity. This suggests that treatment-seeking youth may represent a distinct group that is at particularly high risk for the development of future cardiometabolic disease.

Factors associated with long-term weight-loss maintenance following bariatric surgery in adolescents with severe obesity.

BACKGROUND/OBJECTIVES: Bariatric surgery produces robust weight loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery are unknown. SUBJECTS/METHODS: Fifty adolescents (mean±s.d. age and body mass index (BMI)=17.1±1.7 years and 59±11 kg m-2) underwent Roux-en-Y gastric bypass surgery, had follow-up visits at 1 year and at a visit between 5 and 12 years following surgery (Follow-up of Adolescent Bariatric Surgery at 5 Plus years (FABS-5+) visit; mean±s.d. 8.1±1.6 years). A non-surgical comparison group (n=30; mean±s.d. age and BMI=15.3±1.7 years and BMI=52±8 kg m-2) was recruited to compare weight trajectories over time. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life (QOL), international physical activity questionnaire and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post hoc, participants were split into two groups: long-term weight-loss maintainers (n=23; baseline BMI=58.2 kg m-2; 1-year BMI=35.8 kg m-2; FABS-5+ BMI=34.9 kg m-2) and re-gainers (n=27; baseline BMI=59.8 kg m-2; 1-year BMI=36.8 kg m-2; FABS-5+ BMI=48.0 kg m-2) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status and length of follow-up. RESULTS: The BMI of the surgical group declined from baseline to 1 year (-38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (-29.6±13.9% change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and eating behaviors, health responsibility, physical activity/inactivity, or dietary habits were observed between groups. However, at FABS-5+, maintainers had greater overall QOL scores than re-gainers (87.5±10.5 vs 65.4±20.2, P<0.001) and in each QOL sub-domain (P<0.01 all). CONCLUSIONS: Long-term weight outcomes for those who underwent weight-loss surgery were superior to those who did not undergo surgical treatment. While no behavioral factors were identified as predictors of success in long-term weight-loss maintenance, greater QOL was strongly associated with maintenance of weight loss among adolescents who underwent Roux-en-Y gastric bypass surgery surgery.

Effect of phentermine on weight reduction in a pediatric weight management clinic.

Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care (SOC) lifestyle modification therapy versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3 and 6 months were evaluated using generalized estimated equations adjusting for age, sex and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (-1.6%; 95% confidence interval (CI): -2.6, -0.6%; P=0.001), 3 months (-2.9%; 95% CI: -4.5, -1.4%; P<0.001) and 6 months (-4.1%; 95% CI: -7.1, -1.0%; P=0.009) compared with SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared with SOC-only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.

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.

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.

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.