Aims/hypothesis The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity. Methods Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk. Results The COVID-19 pandemic was associated with increased time-varying BMI ( β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months ( β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI ( β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months ( β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months ( β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively). Conclusions/interpretation Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes. Graphical Abstract

Fragestellung Steck et al. zeigten, dass CGM-Werte bei Time above (TA) >140 mg/dl von über 10% in Personen mit ≥ 1 Inselautoantikörper mit einer schnellen Progression zu einem Stadium 3 T1D assoziiert sind. In unserer Studie untersuchen wir, ob CGM-Messungen bei Kindern der Fr1da-Studie mit ≥ 1 Inselautoantikörper mit HbA1c, oraler Glukosetoleranztest (OGTT) und den jeweiligen Frühstadien 1 und 2 des T1D korrelieren.

ZUSAMMENFASSUNGTechnologischer Fortschritt und das Verständnis der zugrunde liegenden Immunpathogenese der Erkrankung Diabetes mellitus Typ 1 (T1D) haben zu Veränderungen in den präventiven und therapeutischen Ansätzen geführt. Diese zielen darauf ab, das Entstehen des Autoimmunprozesses zu verhindern oder dessen Voranschreiten zumindest zu verlangsamen bzw. die Zerstörung von Betazellen aufzuhalten oder hinauszuzögern. Die Zulassung erster Medikamente für den Einsatz bei Kindern und Jugendlichen im fortgeschrittenen Frühstadium oder kurz nach klinischer Manifestation ist bereits in Aussicht 1.

Background: Antibody responses to virus reflect exposure and potential protection. Methods: We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveilance. Antibody positivity was defined as a dual-positive response against both the receptor-binding domain and nucleocapsid proteins of SARS-CoV-2 Antibodies were measured by immunopreciptation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (ClinicalTrials.gov: NCT04039945) in 1,916 dried blood spots from neonates in a Bavarian screening study (ClinicalTrials.gov: NCT03316261), and in 75 SARS-CoV-2 positive individuals. Virus positive incidence was obtained from the Bavarian health authority data. Findings: Dual-antibody positivity was detected in none of the 3,887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2-positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in Apr 0.74% in May, 1.13% in June. and 0.91% in July. Antibody prevaence from Apr 2020 was 6. fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (p < 0.0001), and was not associated with age or sex Transmission in children with virus positive family members was 35%. 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. Conclusions: We demonstrate the value of population-based screening programs for pandemic monitoring.

The incidence of type 1 diabetes is increasing, especially in young children. Early diagnosis is possible in the asymptomatic stage of islet autoimmunity. Screening is offered to high-risk families, but also feasible and useful in the general population, in studies such as Fr1da(plus)in Bavaria (Germany). Complications at clinical manifestation can be prevented by early diagnosis. Participation in experimental interventions to delay stage progression is possible. Numerous approaches to secondary prevention are being pursued. Treatment with the monoclonal antibody teplizumab successfully delayed progression to clinical diabetes in patients in stage 2. Infants at high risk for developing type 1 diabetes can be identified by genetic screening. Primary prevention pursues, among others, the goal of preventing the onset of the autoimmune reaction. The POInT trial aims to improve immune tolerance to insulin by oral exposure in high-risk children and to delay or prevent the onset of autoimmunity. Following up on the focus issue "Early detection and preventive treatment of type 1 diabetes" published in this journal in 2018, this article gives an update on selected developments over the past 2 years.

Die Inzidenz des Typ-1-Diabetes nimmt zu, besonders bei Kleinkindern. Die Erkrankung kann effektiv bereits im asymptomatischen Frühstadium der Inselautoimmunität erkannt werden. Ein Screening ist nicht nur für Risikofamilien, sondern auch in bevölkerungsweiten Studien wie Fr1daplus in Bayern möglich und sinnvoll. Komplikationen bei der Manifestation kann durch eine frühe Diagnosestellung vorgebeugt werden. Die Teilnahme an experimentellen Interventionen zur Verzögerung der Stadienprogression ist möglich. Unterschiedliche Ansätze zur sekundären Prävention werden verfolgt. Mit dem monoklonalen Antikörper Teplizumab gelang es erstmals, bei Patienten in Stadium 2 den Zeitpunkt der Manifestation hinauszuzögern. Säuglinge mit einem hohen Risiko für die Entwicklung eines Typ-1-Diabetes können durch genetisches Screening identifiziert werden. Bei der Primärprävention wird u. a. das Ziel verfolgt, das Entstehen der Autoimmunreaktion zu verhindern. In der POInT-Studie sollen bei Risikokindern durch frühe orale Exposition zu Insulin die Immuntoleranz verbessert und das Auftreten eines Frühstadiums verzögert oder verhindert werden. Anknüpfend an das Leitthemenheft Früherkennung und präventive Behandlung des Typ-1-Diabetes dieser Zeitschrift von 2018 werden in diesem Beitrag ausgewählte Entwicklungen als Update der letzten 2 Jahre vorgestellt.