DIPP-aineiston hallinnan ja avaamisen haasteet DIPP – Finnish Type 1 Diabetes Prediction and Prevention Study Jorma Toppari University of Turku Tämä teos on lisensoitu Creative Commons Nimeä 4.0 Kansainvälinen -käyttöluvalla. Tarkastele käyttölupaa osoitteessa

Karvonen et al. 1993

Harjutsalo et al. JAMA 2013

Devendra et al. BMJ 2004;328: Natural history of type 1 diabetes

Age at seroconversion in all autoantibody positive children (A; N=1320), and in children who progressed to clinical T1D (B; N=184) Parikka et al. Diabetologia 2012

Probability of progressing to T1D Ziegler et al. JAMA 2013 Germany Finland USA

DIPP Study The Finnish Type 1 Diabetes Prediction and Prevention Study Since 1994 – Ongoing follow-up – Ongoing recruitment Three Clinical Centers – Oulu – Tampere – Turku HLA-DRB1-DQB1 genotyping from cord blood – Newborn infants with increased HLA-conferred T1D risk are invited to the follow-up study babies are screened annually – 840 start follow-up Russia NORWAY SWEDEN OULU TAMPERE TURKU

DIPP Study Follow-up of children with increased HLA-conferred risk for T1D Birth3mo6mo1,5 yr1yr2 yrDIPP follow-up continues once a year up to the age of 15 yrs. Family is informed about the genetic diabetes risk Invitation to participate the follow-up if T1D risk is increased (3-4% or 8-10%) First visit to the DIPP clinic. Informed consent for regular follow-up. Samples from the mother and the baby. Follow-up visits at the DIPP clinic Collection of clinical data and biological samples 9mo Islet antibody negative children will have 19 visits by the age of 15 years. Children turning antibody positive at the age of 1 year will have 60 visits by the age of 15 years if they do not develop T1D.

DIPP newborn screening since 1994 N=206,707 Current DIPP follow-up cohort N=7158 Progressed to T1D during DIPP follow-up N=461 Screening ongoing – /yr ≥ 2 AAB+ (IAA, GADA, IA-2A), N=394 ≥ 2 AAB+ (ICA, IAA, GADA, IA-2A), N=708 Data and sample collection ongoing ~23 new cases/yr HLA eligible (9.4%) invited for follow-up Status of the DIPP Study eligible/yr new children starting follow-up/yr

DIPP Biorepository # Children# SamplesStorage Transport DNA, filter paper RTRegular mail DNA, extracted CDry ice Serum /- 80 CDry ice Plasma CDry ice PBMC CDry ice Buffy coat CDry ice RNA CDry ice Stool /- 70 CRegular mail In addition, questionnaire data (dietary records, infections, vaccinations, medications, allergies, family history) and hair samples have been collected.

SUMMARY Sample and visit statistics Turku Blood samples/year 80,000  Sent to analysis  Sent to analysis25,000  Stored at site  Stored at site55,000 Samples/workday370 Tubes sent/workday 100 Visits to DIPP clinic/year 4,600 IVGTT, OGTT/year 80

Parallel studies TEDDY, The Environmental Determinants of Diabetes in the Young; NIH/NIDDK TrialNet; NIH/NIDDK, JDRF Trigr; NIH/NIDDK (Oulu and Tampere) TEDDY Family Follow-up; JDRF Incretin-mediated prevention of T1D; JDRF

DIPP Funding Academy of Finland – Centre of Excellence of Molecular Systems Immunology and Physiology JDRF Sigrid Juselius Foundation University Hospital Governmental Grants

ATT Personal protection of the study subjects, confidentiality, trustfulness Good science, including ethics, innovations, good common sense Immaterial rights of the universities, hospital districts, researchers Resilience, care of future

DIPP Partners Chair of the DIPP Steering Committee: Riitta Veijola, University of Oulu DIPP Clinical Center PIs: Mikael Knip: University of Helsinki and Tampere University Hospital Jorma Toppari : University of Turku and Turku University Hospital Riitta Veijola : University of Oulu and Oulu University Hospital Jorma Ilonen: University of Turku (DIPP PI, HLA screening and Genetics) Heikki Hyöty: University of Tampere (DIPP PI, Virology)