Search

BackgroundRace/ethnicity and low English proficiency healthcare disparities are well established in the United States. We sought to determine if there are race/ethnicity differences in anti-obesity medication (AOM) prescription rates among youth with severe obesity treated in a pediatric weight management clinic and if, among youth from non-primary English speaking families, there are differences in prescriptions between those using interpreters during visits versus not.MethodsWe reviewed electronic health records of 2- to 18-year-olds with severe obesity seen from 2012 to 2021. Race/ethnicity was self-report, and AOMs included topiramate, stimulants (e.g. phentermine, lisdexamfetamine), naltrexone (±bupropion), glucagon-like peptide-1 agonists, and orlistat. We used general linear regression models with log-link to compare incidence rate ratios (IRRs) within the first 1 and 3 years of being followed, controlling for age, percent of the 95th BMI percentile (%BMIp95), number of obesity-related comorbidities (e.g. insulin resistance, hypertension), median household income, and interpreter use. We repeated similar analyses among youth from non-primary English speaking families, comparing those using interpreters versus not.Results1,725 youth (mean age 11.5 years; %BMIp95 142%; 53% non-Hispanic White, 20% Hispanic/Latino, 16% non-Hispanic black; 6% used interpreters) were seen, of which 15% were prescribed AOMs within 1 year. The IRR for prescriptions was lower among Hispanic/Latino compared to non-Hispanic White youth at one (IRR 0.70; CI: 0.49-1.00; p = 0.047) but not 3 years. No other statistically significant differences by race/ethnicity were found. Among non-primary English speaking families, the IRR for prescriptions was higher at 1 year (IRR 2.49; CI: 1.32-4.70; p = 0.005) in those using interpreters versus not.ConclusionsAmong youth seen in a pediatric weight management clinic, AOM prescription incidence rates were lower in Hispanics/Latinos compared to non-Hispanic Whites. Interpreter use was associated with higher prescription incidence rates among non-primary English speakers. Interventions to achieve equity in AOM prescriptions may help mitigate disparities in pediatric obesity.

Background: Paediatric obesity is a global public health concern. While in most countries the incidence keeps rising, the need for effective and long‐term management for children and adolescents living with this chronic, relapsing disease is pressing. Health behaviour and lifestyle treatment (HBLT) is recommended as first‐line treatment. Methods: Narrative review. Results: A new generation of recently approved anti‐obesity medications (AOM) now has the potential to fill the gap between limited effects on body mass index (BMI) by HBLT alone and large effects by metabolic and bariatric surgery in adolescents with obesity aged 12 years and older. While, for semaglutide and phentermine/topiramate, effectiveness is substantial with relevant, but mostly mild to moderate adverse events, there is a gap in evidence regarding long‐term effects and safety, effects on outcomes beyond BMI reduction and data for certain groups of patients, such as children < 12 years and minority groups. When integrating AOM treatment into national healthcare systems it should be offered as part of a comprehensive patient‐centred approach. Conclusion: This article summarizes recent AOM developments, integration into paediatric obesity management, and identifies research gaps. [ABSTRACT FROM AUTHOR]

Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a "structural vascular age" of at least 40 years old.

Summary: Anti‐obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long‐term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end‐points, secondary end‐points, eligibility criteria, trial run‐in and follow‐up phases, use of active comparators and guidelines for down‐titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end‐points, emphasis was placed on moving away from BMI z‐score as a primary outcome, incorporating multiple alternative BMI‐related outcomes and measuring adiposity/body fat as a prominent secondary end‐point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run‐in phases was discussed. It was also underscored that designing trials with extended follow‐up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo‐controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down‐titration to avoid excessive weight reduction when applicable. [ABSTRACT FROM AUTHOR]

Importance: Obesity affects approximately 21% of US adolescents and is associated with insulin resistance, hypertension, dyslipidemia, sleep disorders, depression, and musculoskeletal problems. Obesity during adolescence has also been associated with an increased risk of mortality from cardiovascular disease and type 2 diabetes in adulthood. Observations: Obesity in adolescents aged 12 to younger than 18 years is commonly defined as a body mass index (BMI) at the 95th or greater age- and sex-adjusted percentile. Comprehensive treatment in adolescents includes lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Lifestyle modification therapy, which includes dietary, physical activity, and behavioral counseling, is first-line treatment; as monotherapy, lifestyle modification requires more than 26 contact hours over 1 year to elicit approximately 3% mean BMI reduction. Newer antiobesity medications, such as liraglutide, semaglutide, and phentermine/topiramate, in combination with lifestyle modification therapy, can reduce mean BMI by approximately 5% to 17% at 1 year of treatment. Adverse effects vary, but severe adverse events from these newer antiobesity medications are rare. Surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) for severe adolescent obesity (BMI ≥120% of the 95th percentile) reduces mean BMI by approximately 30% at 1 year. Minor and major perioperative complications, such as reoperation and hospital readmission for dehydration, are experienced by approximately 15% and 8% of patients, respectively. Determining the long-term durability of all obesity treatments warrants future research. Conclusions and Relevance: The prevalence of adolescent obesity is approximately 21% in the US. Treatment options for adolescents with obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Intensive lifestyle modification therapy reduces BMI by approximately 3% while pharmacotherapy added to lifestyle modification therapy can attain BMI reductions ranging from 5% to 17%. Surgery is the most effective intervention for adolescents with severe obesity and has been shown to achieve BMI reduction of approximately 30%. This Review summarizes the current evidence regarding the epidemiology, pathophysiology, diagnosis, and treatment of obesity in adolescents, with a focus on management of obesity. [ABSTRACT FROM AUTHOR]

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

BackgroundExercise stimulates bone remodeling and improves insulin sensitivity (Si), even without associated weight loss. Osteocalcin (OCN), a bone-derived protein, is associated with improved Si.PurposeWe examined how daily physical activity is associated with OCN and Si.MethodsPhysical activity was measured through questionnaires completed in Minneapolis from 2010-2012. A physical activity score (PAQsum) was calculated to quantify physical activity (range 1-5). OCN and bone specific alkaline phosphatase (BAP) were measured by ELISA. Si was measured by the insulin modified frequently sampled IV glucose tolerance test.ResultsThe mean PAQsum value was 2.4±0.8 in 47 participants (12-17.9 years old). PAQsum was positively associated with OCN (p= 0.006). Participants with PAQsum2 (p

Background: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence. Aims: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity. Methods: The panel was held in Leesburg, Virginia in September 2019. Results: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice guidelines (CPG) to better reflect obesity's pathophysiological basis and heterogeneity, as well as the disease's health, sociocultural, and economic complications; effects on quality of life; need for standards for quantitative comparison of treatment benefits, risks, and costs; and the need to more effectively integrate obesity treatment guidelines into routine clinical practice and to facilitate more direct clinician participation to improve public understanding of obesity as a disease with a pathophysiological basis. The panel also recommended that professional organizations working to improve the care of people with obesity collaborate via a working group to develop an updated, patient‐focused, comprehensive CPG establishing standards of care, addressing identified needs, and providing for routine, periodic review and updating. Conclusions: Unmet needs in the definition, assessment and treatment of obesity were identified and a blueprint to address these needs developed via a clinical practice guideline that can be utilized worldwide to respond to the increasing prevalence of obesity. [ABSTRACT FROM AUTHOR]

Summary: Background: Anti‐obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real‐world' AOM effectiveness and characteristics predicting response is important. Objectives: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. Methods: This was a retrospective cohort study among youth seen in a US academic‐based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating‐related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. Results: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5‐month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3‐ (p = 0.001) and 6‐month (p < 0.001) reductions. Conclusions: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Whilst glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1‐RA) versus placebo in adolescents with severe obesity. Methods: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once‐weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post‐meal replacement therapy (pre‐randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. Results: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. Conclusions: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1‐RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours. [ABSTRACT FROM AUTHOR]

Summary: Importance: The effectiveness of anti‐obesity medications for children and adolescents is unclear. Objective: To update the evidence on the benefits and harms of anti‐obesity medication. Data Sources: Cochrane CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP (1/1/16–17/3/23). Study Selection: Randomized controlled trials ≥6 months in people <19 years living with obesity. Data Extraction and Synthesis: Screening, data extraction and quality assessment conducted in duplicate, independently. Main Outcomes and Measures: Body mass index (BMI): 95th percentile BMI, adverse events and quality of life. Results: Thirty‐five trials (N = 4331), follow‐up: 6–24 months; age: 8.8–16.3 years; BMI: 26.2–41.7 kg/m2. Moderate certainty evidence demonstrated a −1.71 (95% confidence interval [CI]: −2.27 to −1.14)‐unit BMI reduction, ranging from −0.8 to −5.9 units between individual drugs with semaglutide producing the largest reduction of −5.88 kg/m2 (95% CI: −6.99 to −4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: −11.88 percentage points (95% CI: −18.43 to −5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I2 = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance. Conclusions and Relevance: Anti‐obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event. [ABSTRACT FROM AUTHOR]