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.

Rising NAFLD and metabolic severity during the Sars-CoV-2 pandemic among children with obesity in the United States.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), the most common liver disease among youth with obesity, precedes more severe metabolic and liver diseases. However, the impact of the Sars-CoV-2 global pandemic on the prevalence and severity of NAFLD and the associated metabolic phenotype among youth with obesity is unknown. METHODS: Participants were recruited from the Yale Pediatric Obesity Clinic during the Sars-CoV-2 global pandemic (August 2020 to May 2022) and were compared with a frequency-matched control group of youth with obesity studied before the Sars-CoV-2 global pandemic (January 2017 to November 2019). Glucose metabolism differences were assessed during an extended 180-minute oral glucose tolerance test. Magnetic resonance imaging-derived proton density fat fraction (PDFF) was used to determine intrahepatic fat content in those with NAFLD (PDFF ≥ 5.5). RESULTS: NAFLD prevalence increased in participants prior to (36.2%) versus during the Sars-CoV-2 pandemic (60.9%), with higher PDFF values observed in participants with NAFLD (PDFF ≥ 5.5%) during versus before the pandemic. An increase in visceral adipose tissue and a hyperresponsiveness in insulin secretion during the oral glucose tolerance test were also observed. CONCLUSIONS: Hepatic health differences were likely exacerbated by environmental and behavioral changes associated with the pandemic, which are critically important for clinicians to consider when engaging in patient care to help minimize the future risk for metabolic perturbations.

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.

Changes in Weight-Related Health Behaviors and Social Determinants of Health among Youth with Overweight/Obesity during the COVID-19 Pandemic.

Objectives: To assess changes in weight-related health behaviors and social determinants of health (SDoH) among youth with overweight/obesity during the coronavirus disease 2019 (COVID-19) pandemic. Methods: We assessed weight-related health behaviors (physical activity, screen time, sleep, and diet) and SDoH (food insecurity, income/childcare, and caregivers' perceived stress) before vs. during the pandemic with a survey administered August-October 2020 to caregivers of 2-17-year olds and adolescents 13-17 years old with BMI ≥85th percentile seen in clinic within 6 months prepandemic. We analyzed changes in continuous variables using paired t-tests and categorical variables with McNemar's or Fisher's exact tests, and the influence of social determinants on behavior change using multivariable regression models. Results: A total of 129 caregivers and 34 adolescents completed surveys. Compared with prepandemic, caregivers reported youth decreased moderate/vigorous physical activity (-87.4 [205.7] minutes/week, p < 0.001) and increased recreational screen time (2.5 [2.1] hours/day, p < 0.001). Fewer had regular bedtimes (before: 89% and during: 44%, p < 0.001) and more ate most meals with television (before: 16% and during: 36%, p < 0.001). Food insecurity increased from 27% to 43% (p < 0.001), 45% reported reduced household income, and caregivers with moderate/high perceived stress scale scores increased from 43% to 64% (p < 0.001). Moderate/high caregiver stress and food insecurity were associated with greater magnitudes of adverse behavior change. Conclusion: Alarming changes in health behaviors among youth with overweight/obesity, particularly among those with stressed caregivers and food insecurity, may increase prevalence of obesity-related comorbidities and exacerbate health disparities. There is an urgent need to expand access to effective interventions for overweight/obesity that address psychosocial stressors.

Tight junction structure, function, and assessment in the critically ill: a systematic review.

BACKGROUND: Epithelial and endothelial barrier integrity, essential for homeostasis, is maintained by cellular boarder structures known as tight junctions (TJs). In critical illness, TJs may become disrupted, resulting in barrier dysfunction manifesting as capillary leak, pulmonary edema, gut bacterial translocation, and multiple organ failure. We aim to provide a clinically focused overview of TJ structure and function and systematically review and analyze all studies assessing markers of endothelial and epithelial TJ breakdown correlated with clinical outcomes in critically ill humans. METHODS: We systematically searched MEDLINE, EMBASE, and PubMed. Additional articles were identified by targeted searches. We included studies that looked at the relationship between biomarkers of endothelial or epithelial TJ structure or function and critical illness. Results were qualitatively analyzed due to sample size and heterogeneity. RESULTS: A total of 5297 abstracts met search criteria, of which 150 articles met requirements for full text review. Of these, 30 studies met inclusion criteria. Fifteen of the 30 reports investigated proteins of endothelial tight junctions and 15 investigated epithelial TJ markers, exclusively in the gastrointestinal epithelium. No studies investigated TJ-derived proteins in primary cardiac or pulmonary pathology. CONCLUSIONS: TJ integrity is essential for homeostasis. We identified multiple studies that indicate TJs are disrupted by critical illness. These studies highlight the significance of barrier disruption across many critical disease states and correlate TJ-associated markers to clinically relevant outcomes. Further study on the role of multiple tissue-specific claudins, particularly in the setting of respiratory or cardiac failure, may lead to diagnostic and therapeutic advances. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered in the PROSPERO database: CRD42017074546 .

Search Engine Ranking, Quality, and Content of Web Pages That Are Critical Versus Noncritical of Human Papillomavirus Vaccine.

PURPOSE: Online information can influence attitudes toward vaccination. The aim of the present study was to provide a systematic evaluation of the search engine ranking, quality, and content of Web pages that are critical versus noncritical of human papillomavirus (HPV) vaccination. METHODS: We identified HPV vaccine-related Web pages with the Google search engine by entering 20 terms. We then assessed each Web page for critical versus noncritical bias and for the following quality indicators: authorship disclosure, source disclosure, attribution of at least one reference, currency, exclusion of testimonial accounts, and readability level less than ninth grade. We also determined Web page comprehensiveness in terms of mention of 14 HPV vaccine-relevant topics. RESULTS: Twenty searches yielded 116 unique Web pages. HPV vaccine-critical Web pages comprised roughly a third of the top, top 5- and top 10-ranking Web pages. The prevalence of HPV vaccine-critical Web pages was higher for queries that included term modifiers in addition to root terms. Compared with noncritical Web pages, Web pages critical of HPV vaccine overall had a lower quality score than those with a noncritical bias (p < .01) and covered fewer important HPV-related topics (p < .001). Critical Web pages required viewers to have higher reading skills, were less likely to include an author byline, and were more likely to include testimonial accounts. They also were more likely to raise unsubstantiated concerns about vaccination. CONCLUSIONS: Web pages critical of HPV vaccine may be frequently returned and highly ranked by search engine queries despite being of lower quality and less comprehensive than noncritical Web pages.