One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program.

BACKGROUND & AIMS: Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. METHODS: This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon sign rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. RESULTS: Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. CONCLUSIONS: This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

Historical Insights and Current Perspectives on the Diagnosis and Management of Presymptomatic Type 1 Diabetes.

Objective: The article provides practical guidance for (1) interpreting and confirming islet autoantibody screening results for type 1 diabetes (T1D) and (2) follow-up of individuals with early stages of T1D with the goal of ensuring medical safety and providing patients and their families with an assessment of risk for progression to a clinical diagnosis of T1D. Research Design and Methods: We used an explicit a priori methodology to identify areas of agreement and disagreement in how to manage patients with early T1D. We used a modified Delphi method, which is a systematic, iterative approach to identifying consensus. We developed a list of topic questions, ranked them by importance, and developed consensus statements based on available evidence and expert opinion around each of the 30 topic questions consistently ranked as being most important. Results: Consensus statements for screening and monitoring are supported with figures proposing an algorithm for confirmation of T1D diagnosis and management of early T1D until clinical diagnosis. Conclusions: Disseminating and increasing knowledge related to how to interpret T1D screening tests, confirm early T1D diagnosis and monitor for medical safety and clinical disease risk prediction is critically important as there are currently no clinical recommendations. Published guidance will promote better management of T1D screening-detected individuals.

Racial Disparities in Diabetes Technology Adoption and Their Association with HbA1c and Diabetic Ketoacidosis.

Aim: Poorer glycemic control and higher diabetic ketoacidosis (DKA) rates are seen in racial/ethnic minorities with type 1 diabetes (T1D). Use of diabetes technologies such as continuous glucose monitors (CGM), continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) systems has been shown to improve glycemic control and reduce DKA risk. We examined race/ethnicity differences in diabetes technology use and their relationship with HbA1c and DKA. Methods: Data from patients aged ≥12 years with T1D for ≥1 year, receiving care from a single diabetes center, were examined. Patients were classified as Non-Hispanic White (n=3945), Non-Hispanic Black (Black, n=161), Hispanic (n=719), and Multiracial/Other (n=714). General linear models and logistic regression were used. Results: Black (OR=0.22, 0.15-0.32) and Hispanic (OR=0.37, 0.30-0.45) patients were less likely to use diabetes technology. This disparity was greater in the pediatric population (p-interaction=0.06). Technology use associated with lower HbA1c in each race/ethnic group. Among technology users, AID use associated with lower HbA1c compared to CGM and/or CSII (HbA1c of 8.4% vs 9.2%, respectively), with the greatest difference observed for Black adult AID users. CSII use associated with a lower odds of DKA in the past year (OR=0.73, 0.54-0.99), a relationship that did not vary by race (p-interaction =0.69); this inverse association with DKA was not observed for CGM or AID. Conclusion: Disparities in diabetes technology use, DKA, and glycemic control were apparent among Black and Hispanic patients with T1D. Differences in technology use ameliorated but did not fully account for disparities in HbA1c or DKA.

Prevalence of SARS-CoV-2 Antibodies Among Healthy Children From Colorado From 2020 to 2021: A Brief Report.

There are few estimates of the seroprevalence of SARS-CoV-2 antibodies among children in the United States. We measured vaccine and infection induced seroprevalence among nearly 5000 healthy 1 to 17-year-old children in Colorado from 2020 to 2021. By December 2021, 89% of older children, ages 12 to 18, had antibodies detected. The increase was largely driven from vaccination rather than infection.

Previous SARS-CoV-2 Infection Is Not Associated With Increased Celiac Disease Autoimmunity in Children and Adolescents.

INTRODUCTION: Recent reports suggest severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections may increase the risk of celiac disease autoimmunity. This study aims to evaluate potential associations between coronavirus disease 2019 infection and tissue transglutaminase autoantibodies (TGA) immunoglobulin A. METHODS: From 2020 to 2021, cross-sectional screening for SARS-CoV-2 antibodies and TGA was offered to 4,717 children in Colorado through the Autoimmunity Screening for Kids study. Multivariable logistic regression assessed association between previous SARS-CoV-2 infection and TGA positivity. RESULTS: Previous SARS-CoV-2 infection was not associated with TGA positivity (odds ratio 1.02, 95% confidence interval 0.63-1.59; P = 0.95). DISCUSSION: In this large-scale analysis, previous SARS-CoV-2 infection was not associated with celiac disease autoimmunity in Colorado children.

SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany.

This study screens more than 50 000 youths in diverse populations of Colorado and Bavaria to assess whether previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective.

Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established.

CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study.

OBJECTIVE: Children identified with stage 1 type 1 diabetes are at high risk for progressing to stage 3 (clinical) diabetes and require accurate monitoring. Our aim was to establish continuous glucose monitoring (CGM) metrics that could predict imminent progression to diabetes. RESEARCH DESIGN AND METHODS: In the Autoimmunity Screening for Kids study, 91 children who were persistently islet autoantibody positive (median age 11.5 years; 48% non-Hispanic White; 57% female) with a baseline CGM were followed for development of diabetes for a median of 6 (range 0.2-34) months. Of these, 16 (18%) progressed to clinical diabetes in a median of 4.5 (range 0.4-29) months. RESULTS: Compared with children who did not progress to clinical diabetes (nonprogressors), those who did (progressors) had significantly higher average sensor glucose levels (119 vs. 105 mg/dL, P < 0.001) and increased glycemic variability (SD 27 vs. 16, coefficient of variation, 21 vs. 15, mean of daily differences 24 vs. 16, and mean amplitude of glycemic excursions 43 vs. 26, all P < 0.001). For progressors, 21% of the time was spent with glucose levels >140 mg/dL (TA140) and 8% of time >160 mg/dL, compared with 3% and 1%, respectively, for nonprogressors. In survival analyses, the risk of progression to diabetes in 1 year was 80% in those with TA140 >10%; in contrast, it was only 5% in the other participants. Performance of prediction by receiver operating curve analyses showed area under the curve of ≥0.89 for both individual and combined CGM metric models. CONCLUSIONS: TA140 >10% is associated with a high risk of progression to clinical diabetes within the next year in autoantibody-positive children. CGM should be included in the ongoing monitoring of high-risk children and could be used as potential entry criterion for prevention trials.

Prevalence of SARS-CoV-2 Antibodies in Children and Adults with Type 1 Diabetes.

Objective: As diabetes is a risk factor for severe symptoms, hospitalization, and death with COVID-19 disease, we aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in children and adults with and without type 1 diabetes in Colorado during 2020. Research Design and Methods: We developed a highly sensitive and specific test for antibodies against SARS-CoV-2 and measured the antibodies in children and adults with new-onset (n = 129) and established type 1 diabetes (n = 94) seen for routine diabetes care at our center between January and October 2020. The antibodies were also measured in 562 children and 102 adults from the general population of Colorado. Results: The prevalence of SARS-CoV-2 antibodies in persons with new-onset type 1 diabetes (0.8%; 95% confidence interval 0.1%-4.2%) or those with established disease (4.3%; 1.7%-10.4%) did not differ from that in the general population children (2.8%; 1.8%-4.6%) or adults (3.9%; 1.5%-9.7%). In a subset of individuals with positive antibodies (n = 31), antibodies remained positive for up to 9 months, although the levels decreased starting 3 months after the infection (P = 0.007). Conclusions: From January to October 2020, the prevalence of SARS-CoV-2 antibodies were not different in children and adults with and without type 1 diabetes in Colorado. We found no evidence for increased prevalence of COVID-19 infections among youth with newly diagnosed type 1 diabetes. (COMIRB Protocol 20-1007).

Mass Screening for Celiac Disease: The Autoimmunity Screening for Kids Study.

INTRODUCTION: The Autoimmunity Screening for Kids (ASK) study is a large scale pediatric screening study in Colorado for celiac disease (CD) and type 1 diabetes. This is a report of the CD outcomes for the first 9,973 children screened through ASK. METHODS: ASK screens children aged 1-17 years for CD using 2 highly sensitive assays for tissue transglutaminase autoantibodies (TGA): a radiobinding (RBA) assay for IgA TGA and an electrochemiluminescence (ECL) assay that detects all TGA isotypes. Children who test positive on either assay are asked to return for confirmatory testing. Those with a confirmed RBA TGA level ≥ 0.1 (twice the upper limit of normal) are referred to the Colorado Center for Celiac Disease for further evaluation; all others are referred to primary care. RESULTS: Of the initial 9,973 children screened, 242 children were TGA+ by any assay. Of those initially positive, 185 children (76.4%) have completed a confirmation blood draw with 149 children (80.5%) confirming positive by RBA TGA. Confirmed RBA TGA+ was associated with a family history of CD (odds ratio [OR] = 1.83; 95% confidence interval 1.06-3.16), non-Hispanic white ethnicity (OR = 3.34; 2.32-4.79), and female sex (OR = 1.43; 1.03-1.98). Gastrointestinal symptoms of CD, assessed at the initial screening, were reported equally often among the RBA TGA+ vs TGA- children (32.1% vs 30.5%, P = 0.65). DISCUSSION: The initial results of this ongoing mass-screening program confirm a high prevalence of undiagnosed CD autoimmunity in a screened US population. Symptoms at initial screening were not associated with TGA status (see Visual abstract, Supplementary Digital Content 5, http://links.lww.com/AJG/B587).

Cost and Cost-effectiveness of Large-scale Screening for Type 1 Diabetes in Colorado.

OBJECTIVE: To assess the costs and project the potential lifetime cost-effectiveness of the ongoing Autoimmunity Screening for Kids (ASK) program, a large-scale, presymptomatic type 1 diabetes screening program for children and adolescents in the metropolitan Denver region. RESEARCH DESIGN AND METHODS: We report the resource utilization, costs, and effectiveness measures from the ongoing ASK program compared with usual care (i.e., no screening). Additionally, we report a practical screening scenario by including utilization and costs relevant to routine screening in clinical practice. Finally, we project the potential cost-effectiveness of ASK and routine screening by identifying clinical benchmarks (i.e., diabetic ketoacidosis [DKA] events avoided, HbA1c improvements vs. no screening) needed to meet value thresholds of $50,000-$150,000 per quality-adjusted life-year (QALY) gained over a lifetime horizon. RESULTS: Cost per case detected was $4,700 for ASK screening and $14,000 for routine screening. To achieve value thresholds of $50,000-$150,000 per QALY gained, screening costs would need to be offset by cost savings through 20% reductions in DKA events at diagnosis in addition to 0.1% (1.1 mmol/mol) improvements in HbA1c over a lifetime compared with no screening for patients who develop type 1 diabetes. Value thresholds were not met from avoiding DKA events alone in either scenario. CONCLUSIONS: Presymptomatic type 1 diabetes screening may be cost-effective in areas with a high prevalence of DKA and an infrastructure facilitating screening and monitoring if the benefits of avoiding DKA events and improved HbA1c persist over long-run time horizons. As more data are collected from ASK, the model will be updated with direct evidence on screening effects.

Improving Nutrition and Physical Activity Policies and Practices in Early Care and Education in Three States, 2014-2016.

The National Early Care and Education Learning Collaboratives (ECELC) project aims to facilitate best practices in nutrition, physical activity, screen time, and breastfeeding support and infant feeding among early care and education (ECE) programs across multiple states. The project uses a train-the-trainer approach with 5, in-person learning-collaborative sessions, technical assistance, and action planning. We describe the longitudinal practice-based evaluation of the project and assess whether ECE programs evaluated (n = 104) sustained changes in policies and practices 1 year after completing the project. The number of best practices increased from pre-assessment to post-assessment (P < .01) but did not change significantly from post-assessment to follow-up assessment. ECELC shows promise as an approach to incorporate professional development and training focused on improving best practices for environment-level child nutrition and physical activity, which is one strategy among many that are warranted for obesity prevention in young children.

Assessment of nutrition and physical activity practices using self-report and observation in early care and education across multiple US states.

OBJECTIVE: The National Early Care and Education Learning Collaboratives (ECELC) Project aims to promote healthy physical activity and nutrition environments, policies and practices in early care and education (ECE) programmes across multiple states. The present pilot study sought to assess changes to the physical activity and nutrition practices in a sub-sample of ECE programmes participating in the ECELC using the Environment and Policy Assessment and Observation (EPAO). Additionally, it sought to compare results with the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC). DESIGN: Quasi-experimental pre-post pilot study where paired-sample t tests examined changes to physical activity and nutrition practices from pre-assessment to post-assessment (P<0·05). Pearson correlation coefficients examined change scores from EPAO compared with NAP SACC with statistical significance set at a two-sided α level of P<0·10 to account for sample size. SETTING: The study occurred among ECE programmes. SUBJECTS: Pre-school classrooms in nineteen ECE programmes across four US states were observed. RESULTS: EPAO data demonstrated an increase in total score from pre-assessment to post-assessment (150 (sd 30) to 176 (sd 35)). NAP SACC change scores demonstrated little relationship with EPAO domain change scores, with exceptions in Nutrition Policy and Physical Activity Policy (r=-0·4 and -0·6, respectively). CONCLUSIONS: The overall improvements reported through the EPAO suggest participation in the ECELC resulted in changes in critical nutrition- and physical activity-related practices. However, considerable differences in data reported using the NAP SACC compared with the EPAO suggest subjective data should be interpreted with caution and objective measurement should be used when feasible.