title: Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study.
abstract: Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care.
  
  
  
  Children aged 2-5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed.
  
  
  
  Of the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies.
  
  
  
  Staging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education.
  
  
  
  The study was approved by the ethics committee of Technische Universität München (Nr. 70/14).
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Raab
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Haupt
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Marlon
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Matzke
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany Forschergruppe Diabetes e.V., Neuherberg, Germany Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Warncke
authors.affiliation: Department of Medical Psychology, Hannover Medical School, Hannover, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Lange
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Assfalg
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weininger
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wittich
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Löbner
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyerlein
authors.affiliation: Bavarian Health and Food Safety Authority, Oberschleißheim, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Nennstiel-Ratzel
authors.affiliation: Berufsverband der Kinder- und Jugendärzte e.V., Landesverband Bayern, Augsburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lang
authors.affiliation: PaedNetz Bayern e.V., Rosenheim, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Laub
authors.affiliation: Klinikum Augsburg, Klinik für Kinder und Jugendliche, Augsburg, Germany.
authors.forename: Desiree
authors.initials: D
authors.lastname: Dunstheimer
authors.affiliation: Centre for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität, Dresden, Germany Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of Technische Universität, Dresden, Germany.
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Winkler
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D001800:Blood Specimen Collection; D002196:Capillaries; D017028:Caregivers / Q000193:education; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D037001:Directive Counseling; D042241:Early Diagnosis; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D010353:Patient Education as Topic; D011236:Prediabetic State / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D000074286:Preliminary Data; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012107:Research Design; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology; D000075703:Zinc Transporter 8 / Q000276:immunology
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: childhood; islet autoantibodies; screening; type 1 diabetes