Real-world use of glucagon-like peptide-1 receptor agonists in youth with type 2 diabetes is associated with short-term improvements in HbA1c.

AIM: To assess the short-term, real-world use and effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) medications in the management of type 2 diabetes (T2D) in a diverse cohort of youth. METHODS: This multicentre retrospective study analysed youth prescribed a GLP-1RA for the management of T2D at two academic paediatric diabetes centres prior to June 2022. Change in HbA1c and insulin use from baseline to first (median 91 days) and second (median 190 days) follow-up were evaluated for those taking a GLP-1RA. Multivariable linear mixed effects models adjusting for baseline sex, age, race/ethnicity, insurance, insulin regimen, metformin regimen, GLP-1RA dosing frequency and the body mass index Z-score (BMI-Z) examined the change in HbA1c for participants for up to 6 months after baseline. RESULTS: A total of 136 patients with T2D (median age 16.1 [interquartile range 13.9-18.0] years, 54% female, 56% non-Hispanic Black, 24% Hispanic, 77% with public insurance) were prescribed GLP-1RAs and taking them at first or second follow-up. Median HbA1c decreased from 7.9% to 7.6% (P < .001) at a median follow-up of 91 days (n = 109) and, among those with HbA1c available at baseline and second follow-up (n = 83), from 8.4% to 7.4%. The proportion of patients prescribed insulin decreased from baseline to the first follow-up visit (basal 69% to 60% [P = .008], prandial 46% to 38% [P = .03]). In multivariable analysis, there was a mean decrease in HbA1c by 0.09 percentage points per month (P = .005, 95% confidence interval -0.15, -0.03). CONCLUSIONS: Real-world use of GLP-1RAs in youth with T2D is associated with decreased HbA1c levels, despite challenges with access and adherence. GLP-1RA treatment may reduce insulin doses for youth with T2D.

Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity.

Importance: Pediatric obesity is a growing health care burden. Understanding how the metabolic phenotype of youth with obesity may modify the effect of intestinal fermentation on human metabolism is key to designing early intervention. Objective: To assess whether adiposity and insulin resistance in youth may be associated with colonic fermentation of dietary fibers and its production of acetate, gut-derived hormone secretion, and adipose tissue lipolysis. Design, Setting, and Participants: Cross-sectional study of youths aged 15 to 22 years with body mass index in the 25th to 75th percentile or higher than the 85th percentile for age and sex throughout the New Haven County community in Connecticut. Recruitment, studies, and data collection occurred from June 2018 to September 2021. Youths were assigned to a lean, obese insulin sensitive (OIS), or obese insulin resistant (OIR) group. Data were analyzed from April 2022 to September 2022. Exposure: Participants consumed 20 g of lactulose during a continuous 10-hour sodium d3-acetate intravenous infusion to measure the rate of appearance of acetate in plasma. Main Outcomes and Measures: Plasma was obtained hourly to measure acetate turnover, peptide tyrosine tyrosine (PYY), ghrelin, active glucagon-like peptide 1 (GLP-1), and free fatty acids (FFA). Results: A total of 44 youths participated in the study (median [IQR] age, 17.5 [16.0-19.3] years; 25 [56.8%] were female; 23 [52.3%] were White). Consequent to lactulose ingestion, there was a reduction of plasma FFA, an improvement of adipose tissue insulin sensitivity index, an increase in colonic acetate synthesis, and an anorexigenic response characterized by an increased plasma concentration of PYY and active GLP-1 and a reduction of ghrelin in the subgroups. Compared with the lean and OIS groups, the OIR group showed a less marked median (IQR) rate of acetate appearance (OIR: 2.00 [-0.86 to 2.69] µmol × kg-1 × min-1; lean: 5.69 [3.04 to 9.77] µmol × kg-1 × min-1; lean vs OIR P = .004; OIS: 2.63 [1.22 to 4.52] µmol × kg-1 × min-1; OIS vs OIR P = .09), a blunted median (IQR) improvement of adipose insulin sensitivity index (OIR: 0.043 [ 0.006 to 0.155]; lean: 0.277 [0.220 to 0.446]; lean vs OIR P = .002; OIS: 0.340 [0.048 to 0.491]; OIS vs OIR P = .08), and a reduced median (IQR) PYY response (OIR: 25.4 [14.8 to 36.4] pg/mL; lean: 51.3 [31.6 to 83.3] pg/mL; lean vs OIR P = .002; OIS: 54.3 [39.3 to 77.2] pg/mL; OIS vs OIR P = .011). Conclusions and Relevance: In this cross-sectional study, lean, OIS, and OIR youth demonstrated different associations between colonic fermentation of indigestible dietary carbohydrates and the metabolic response, with OIR youth showing minimal metabolic modifications as compared with the other 2 groups. Trial Registration: ClinicalTrials.gov Identifier: NCT03454828.

Real-world effectiveness of the Bright Bodies healthy lifestyle intervention for childhood obesity.

OBJECTIVE: This study aimed to examine the extent to which Bright Bodies, a high-intensity, family-based pediatric weight management intervention, improved BMI for participants since publication of the randomized controlled trial establishing efficacy in 2007 and to describe adaptations to the program. METHODS: For participants enrolled from 2008 to 2018, linear mixed-effects models were used to estimate monthly change in BMI expressed as percentage of the 95th percentile (%BMIp95) during participants' first beginner-level program. RESULTS: The sample included 396 youth individuals (mean age: 11.7 [SD 2.8] years, 61.6% female, 37.1% non-Hispanic Black, 26.3% Hispanic or Latino, 53.8% with public insurance, 80.1% with severe obesity). Across the 11 years, participants' %BMIp95 reduced on average by 1.63% (95% CI: 1.44%-1.82%) per month during their first program (mean duration: 10 weeks) after adjusting for age, sex, season and year, starting %BMIp95, race and ethnicity, and insurance category. Greater reduction in %BMIp95 was associated with male versus female sex, spring/fall versus winter seasons, enrollment in 2008 to 2018 versus 2015 to 2018, and higher starting %BMIp95 (p value for all <0.001). Adaptations since 2007 included pragmatic changes to increase engagement and address funding shortages. CONCLUSIONS: These results suggest sustained clinical effectiveness of Bright Bodies in the context of real-world adaptations.

How Forcefully Should Clinicians Encourage Treatment When Disagreement Persists About Obesity Risk?

Pediatric obesity is a major public health problem, and weight reduction in children and adolescents with obesity is associated with improvement in health outcomes. This case of an adolescent diagnosed with obesity whose mother disagrees with the diagnosis illustrates challenges often encountered in clinical practice, including (1) diagnosing a disease in an asymptomatic patient whose future risk for negative health outcomes is uncertain, (2) addressing ethical implications of naming a stigmatizing disease, and (3) resolving conflicting goals and opinions of a patient, caregiver, and physician. Suggestions for navigating disagreement and implementing courses of action are discussed.

Neonatal Thyrotoxicosis.

Neonatal thyrotoxicosis (hyperthyroidism) is less prevalent than congenital hypothyroidism; however, it can lead to significant morbidity and mortality if not promptly recognized and adequately treated. Most cases are transient, secondary to maternal autoimmune hyperthyroidism (Graves disease [GD]). This article summarizes recommendations for screening and management of hyperthyroidism in both the fetal and neonatal periods, with a focus on neonatal thyrotoxicosis secondary to maternal GD. Early monitoring and treatment are crucial for optimizing short-term and long-term patient outcomes.

Characteristics of Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Cohort.

Context: In adults, noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) is considered a low risk for metastasis and persistent/recurrent disease. Objective: The goal of this study was to assess the clinical, sonographic, and histopathologic features of FVPTC in a pediatric cohort. Design: A retrospective review of subjects <19 years of age with papillary thyroid carcinoma (PTC) who underwent thyroidectomy between January 2010 and July 2015. Setting: Multidisciplinary academic referral center. Patients: Patients with FVPTC, defined as a tumor ≥1 cm in the largest dimension with predominant follicular growth, complete lack of well-formed papillae, and nuclear features of PTC. Main Outcome Measures: Tumor size and location, presence of a tumor capsule, capsule and vascular invasion, lymph node invasion, and distant metastasis. Results: Eighteen patients with FVPTC were identified from a case cohort of 110 patients with PTC. On histopathology, 13 (72%) had unifocal nodules and 14 (78%) had completely encapsulated FVPTC. Capsule invasion was frequent (nine of 14; 64%), and vascular invasion was found in one-third of patients (six of 18; 33%). No lymph node metastases were found in the 13 patients (72%) who had a central neck lymph node dissection. One patient with vascular invasion had distant metastases. Conclusion: When strictly defined, FVPTC in pediatric patients has a low risk for bilateral disease and metastasis. Prospective studies are needed to confirm whether lobectomy with surveillance is sufficient to achieve remission in pediatric patients with low-risk FVPTC.