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. 2025 Jan 2;15(1):e088522.
doi: 10.1136/bmjopen-2024-088522.

EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents

Luisa Hoffmann  1 , Mirjam Kohls  1 , Stefanie Arnolds  1 , Peter Achenbach  1   2 , Regine Bergholdt  3 , Ezio Bonifacio  4 , Emanuele Bosi  5   6 , Melanie Gündert  1 , Bianca K Hoefelschweiger  1 , Sandra Hummel  1 , Przemysława Jarosz-Chobot  7 , Olga Kordonouri  8 , Vito Lampasona  5 , Parth Narendran  9 , Lut Overbergh  10 , Flemming Pociot  11 , João Filipe Raposo  12   13 , Zdeněk Šumník  14 , Agnieszka Szypowska  15 , Jurgen Vercauteren  10 , Christiane Winkler  1 , Chantal Mathieu  10   16 , Anette-Gabriele Ziegler  17   2 ; EDENT1FI consortium
Collaborators, Affiliations

EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents

Luisa Hoffmann et al. BMJ Open. .

Abstract

Introduction: The identification of type 1 diabetes at an early presymptomatic stage has clinical benefits. These include a reduced risk of diabetic ketoacidosis (DKA) at the clinical manifestation of the disease and a significant reduction in clinical symptoms. The European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception (EDENT1FI) represents a pioneering effort to advance early detection of type 1 diabetes through public health screening. With the EDENT1FI Master Protocol, the project aims to harmonise and standardise screening for early-stage type 1 diabetes and care.

Methods and analysis: Public health islet autoantibody screening is conducted in the Czech Republic, Denmark, Germany, Italy, Poland, Portugal, Sweden and the UK. Between November 2023 (start date) and October 2028 (planned end date), an estimated number of 200 000 children and adolescents aged 1-17 years are expected to be screened. Screening is performed in capillary blood, examining different islet autoantibodies (autoantibodies against insulin, glutamic acid decarboxylase-65, insulinoma-associated antigen-2 and/or zinc transporter-8). Positive screening results undergo confirmation through a second antibody method. A second (venous) blood sample is requested if at least two autoantibodies are detected, to confirm the autoantibody status. Children and adolescents with confirmed two or more autoantibodies are invited to metabolic staging (oral glucose tolerance test, haemoglobin A1c (HbA1c), random glucose, optionally continuous glucose monitoring); an educational programme and recommendations for monitoring are provided. The feasibility and acceptability of screening are evaluated by feedback questionnaires. Pseudonymised data is collated in the EDENT1FI Registry. Study outcomes include country-specific screening rates, prevalences of stage 1 and stage 2 type 1 diabetes, number in EDENT1FI Registry, proportion with DKA and symptoms at clinical diagnosis and median HbA1c.

Ethics and dissemination: Following the EDENT1FI Master Protocol, site-specific protocols are developed and approved by local ethics committees (Technical University of Munich, Medical Faculty, Nr. 70/14; Medizinische Hochschule Hannover, Nr. 9588_BO_S_2021; Technische Universität Dresden, Nr. BO-EK-356082020; Center for Sundhed Region Hovedstaden, Nr. H-22053116; Swedish Ethical Review Authority, Nr. 2023-00312-01; National Health Service Health Research Authority and Health Care Research Wales, IRAS (Integrated Research Application System) project ID 309252; Italian National Institute of Health, National ethics committee for clinical trials of public research bodies (EPR) and other national public institutions, Prot. PRE BIO CE Nr. 0059835; Charles University in Prague, Ethics Committee for Multi-Centric Clinical Trials of the University Hopital Motol and 2nd Faculty of Medicine, Nr. 1271/23; Bioethics Committee at the Medical University of Warsaw, Nr. 21/2024 and KB/6/R/2024; Associação Protectora dos Diabéticos de Portugal, Nr. 211/2024). Results are disseminated through peer-reviewed journals and conference presentations and will be shared openly.

Keywords: Community child health; General diabetes; PUBLIC HEALTH; Paediatric endocrinology.

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Conflict of interest statement

Competing interests: RB is an employee and shareholder of Novo Nordisk A/S. EBos is a member of a scientific advisory board of Sanofi. CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Eli Lilly and Company, Novartis, Boehringer Ingelheim, Roche, Medtronic, Imcyse, Insulet, Biomea Fusion and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Medtronic, Imcyse, Novo Nordisk, Sanofi and ActoBio Therapeutics; CM serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Medtronic and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. CM is president of EASD. All external support of EASD is to be found on www.easd.org. A-GZ serves or has served on the advisory panel for Sanofi.

Figures

Figure 1
Figure 1. Flowchart showing the screening process for early-stage type 1 diabetes in EDENT1FI. Children and adolescents who have multiple islet autoantibodies detected in two different blood samples and by two different methods are diagnosed with early-stage type 1 diabetes. These individuals will be enrolled in the EDENT1FI Registry and invited to participate in an educational programme and metabolic staging. They will also be offered participation in tandem protocols examining the psychological burden of screening, conducting monitoring studies and intervention studies. EDENT1FI, European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception; GADA, glutamic acid decarboxylase-65; IAA, autoantibodies against insulin; IA-2A, insulinoma-associated antigen-2; TG-A, transglutaminase autoantibodies; TPO-A, thyroid peroxidase autoantibodies; ZnT8A, zinc transporter 8.
See this image and copyright information in PMC

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