Acknowledgements

We gratefully acknowledge all participants of the INNODIA Natural History Study, which forms the basis for the work presented here. Without the outstanding engagement of the people with type 1 diabetes and their relatives and friends participating in the INNODIA clinical efforts, this data and new knowledge gain would not have been possible. The authors also want to thank all the clinical personnel for their dedication in the participant recruitment and characterisation, and sample collection and preparation that was at the basis of this analysis. For the Cambridge site, work was supported by the NIHR Cambridge Biomedical Research Centre and carried out in the NIHR Cambridge Clinical Research Facility/ Translational Research Facility (TRF).

Data availability

The data generated and analysed are person-sensitive and can be accessed in secure environments only. Access can be provided by application to the INNODIA Data Access Committee (innodia.eu).

Funding

INNODIA has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115797 (INNODIA). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation programme, ‘EFPIA’, ‘JDRF’ and ‘The Leona M. and Harry B. Helmsley Charitable Trust’. The University of Cambridge has received salary support for MLE through the National Health Service in the East of England through the Clinical Academic Reserve. JAT and LSW received funding from Wellcome (107212/A/15/Z) and JDRF (4-SRA-2017-473-A-N).

Authors’ relationships and activities

CD is an employee and shareholder of Novo Nordisk. The other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement

CD and SK performed data analyses. MLM contributed to data collection and analyses, and drafted the first version of the manuscript. AEJH, TD, MLE, JJ, MK, FP, LO, CM, TB, BVdS, LSW, JAT and MP collected data and contributed to data interpretation and discussion. CM, MP and MLM designed the study. All authors critically reviewed and commented on the manuscript. All authors have given final approval for this version to be published. CM is responsible for the integrity of the work as a whole

Members of the INNODIA and INNODIA HARVEST consortia

C. Mathieu, P. Gillard, K. Casteels, L. Overbergh (KU Leuven, Belgium); D. Dunger, C. Wallace, M. Evans, A. Thankamony, E. Hendriks, S. Bruggraber, M. L. Marcovecchio, Paediatrics laboratory staff (University of Cambridge, UK); M. Peakman, T. Tree (King’s College London, UK); N. Morgan, S. Richardson (University of Exeter, UK); J. Todd, L. Wicker (University of Oxford, UK); A. Mander, C. Dayan, M. Alhadj Ali (Cardiff University, UK); T. Pieber (Medical University of Graz, Austria); D. Eizirik, M. Cnop (Universite Libre de Bruxelles, Belgium); S. Brunak (University of Copenhagen, Denmark); F. Pociot, J. Johannesen, P. Rossing, C. Legido Quigley (Herlev University Hospital, Region Hovedstaden, Denmark); R. Mallone, R. Scharfmann, C. Boitard (Cochin Institute Paris, France); M. Knip, T. Otonkoski (University of Helsinki, Finland); R. Veijola (University of Oulu, Finland); R. Lahesmaa, M. Oresic, J. Toppari (University of Turku, Finland); T. Danne (Children’s and Youth Hospital Hannover, Germany); A. G. Ziegler, P. Achenbach, T. Rodriguez-Calvo (Helmholtz Zentrum Muenchen, Germany); M. Solimena, E. Bonifacio, S. Speier (TU Dresden, Germany); R. Holl (University of Ulm, Germany); F. Dotta (University of Siena, Italy); F. Chiarelli (University of Chieti, Italy); P. Marchetti (University of Pisa, Italy); E. Bosi (University Vita-Salute San Raffaele, Italy); S. Cianfarani, P. Ciampalini (Bambino Gesù Children’s Hospital, Italy); C. de Beaufort (Centre Hospitalier de Luxembourg, Luxemburg); K. Dahl-Jørgensen, T. Skrivarhaug, G. Joner, L. Krogvold (Oslo University Hospital, Norway); P. Jarosz-Chobot (Medical University of Silesia, Poland); T. Battelino, D. Smigoc Schweiger (University of Ljubljana, Slovenia); B. Thorens (University of Lausanne, Switzerland); M. Gotthardt (Radboud University Medical Center, the Netherlands); B. Roep, T. Nikolic, A. Zaldumbide (Leiden University Medical Center, the Netherlands); A. Lernmark, M. Lundgren (Lund University, Sweden); G. Costeca (Univercell-Biosolutions, France); T. Strube, A. Schulte, A. Nitsche (Sanofi, Germany); M. Peakman, J. Vela (Sanofi, USA); M. von Herrath, J. Wesley (Novo Nordisk, Denmark); A. Napolitano-Rosen (GlaxoSmithKline, UK); M. Thomas, N. Schloot (Eli Lilly, UK); A. Goldfine, F. Waldron-Lynch, J. Kompa, A. Vedala, N. Hartmann, G. Nicolas (Novartis Pharma AG, Switzerland); J. van Rampelbergh, N. Bovy (Imcyse SA, Belgium); S. Dutta, J. Soderberg, S. Ahmed, F. Martin, E. Latres (JDRF, USA); G. Agiostratidou, A. Koralova (The Leona M. and Harry B. Helmsley Charitable Trust, USA).

Associated clinical sites

R. Willemsen (Barts Health NHS Trust, UK); A. Smith (Northampton General Hospital NHS Trust, UK); B. Anand (West Suffolk NHS FT, UK); V. Puthi (North West Anglia NHS FT, UK); S. Zac-Varghese (East & North Hertfordshire NHS Trust, UK); V. Datta (Norfolk & Norwich University NHS FT, UK); R. Dias (Birmingham Women's and Children’s NHS FT, UK); P. Sundaram (University Hospitals of Leicester NHS Trust, UK); B. Vaidya (Royal Devon & Exeter NHS FT, UK); C. Patterson (NHS Fife, UK); K. Owen (Oxford University Hospitals NHS FT, UK); C. Dayan (Cardiff & Vale University Health Board, UK); B. Piel (Queen Elizabeth Hospital, King’s Lynn FT, UK); S. Heller (Sheffield Teaching Hospitals NHS FT, UK); T. Randell, T. Gazis (Nottingham University Hospitals NHS Trust, UK); E. Bismuth Reismen, J.-C. Carel (Hospital Robert Debre, France); J.-P. Riveline, J.-F. Gautier (Hospital Lariboisiere, France); F. Andreelli (Hospital Lapitie-Salpetriere, France); F. Travert (Hospital Bichat Claude Bernard, France); E. Cosson (Hospital Jean-Verdier, France); A. Penfornis, C. Petit (Centre Hospitalier Sud-Francilien, France); B. Feve (Hospital St Antoine, France); N. Lucidarme (Hospital Jean-Verdier Pediatrie, France); E. Cosson (Hospital Avicenne, France); J.-P. Beressi (Hospital Andre Mignot, France); C. Ajzenman (Hospital Andre Mignot Pediatrie, France); A. Radu (Hospital Europeen Georges-Pompidou, France); S. Greteau-Hamoumou (Hospital Louis Mourier, France); C. Bibal (Hospital Kremlin Bicetre, France); T. Meissner (Universitatsklinikum der Heinrich-Heine-Univeritat Dusseldorf, Germany); B. Heidtmann (Katholisches Kinderkrankenhaus Wilhelmstift, Germany); S. Toni (AOU Meyer, Italy); B. Rami-Merhar (Medical University of Vienna, Austria); B. Eeckhout, B. Peene, N. Vantongerloo (Algemeen Ziekenhuis Geel Sint-Dimpna Geel, Belgium); T. Maes, L. Gommers (Imeldziekenhuis Bonheiden, Belgium).