Transcript TEDDY Study Progress overview

DIPP-aineiston hallinnan ja
avaamisen haasteet
DIPP – Finnish Type 1 Diabetes
Prediction and Prevention
Study
Jorma Toppari
University of Turku
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Karvonen et al. 1993
Harjutsalo et al. JAMA 2013
Natural history of type 1 diabetes
Devendra et al. BMJ 2004;328:750-754
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
USA
Finland
Ziegler et al. JAMA 2013
Germany
DIPP Study
The Finnish Type 1 Diabetes Prediction and Prevention Study
• Since 1994
– Ongoing follow-up
– Ongoing recruitment
NORWAY
• Three Clinical Centers
– Oulu
– Tampere
– Turku
• HLA-DRB1-DQB1
genotyping from cord
blood
OULU
SWEDEN
– Newborn infants with
increased HLA-conferred
T1D risk are invited to the
follow-up study
• 11000 babies are
screened annually
– 840 start follow-up
Russia
TURKU
TAMPERE
DIPP Study
Follow-up of children with increased HLA-conferred risk for T1D
Follow-up visits at the DIPP clinic
Collection of clinical data and
biological samples
Family is informed about the
genetic diabetes risk
Invitation to participate the
follow-up if T1D risk is
increased (3-4% or 8-10%)
Birth
3mo
6mo
9mo
First visit to the DIPP clinic.
Informed consent for regular follow-up.
Samples from the mother and the baby.
1yr
1,5 yr
2 yr DIPP follow-up continues
once a year up to the age of
15 yrs.
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.
Status of the DIPP Study 2015
DIPP newborn screening since 1994
N=206,707
HLA eligible (9.4%) invited for
follow-up
Screening ongoing
10 000 – 11 000/yr
1000-1200 eligible/yr
700-840 new children
starting follow-up/yr
Current DIPP follow-up cohort
N=7158
Data and sample
collection ongoing
≥ 2 AAB+ (IAA, GADA, IA-2A), N=394
≥ 2 AAB+ (ICA, IAA, GADA, IA-2A), N=708
Progressed to T1D during DIPP follow-up
N=461
~23 new cases/yr
DIPP Biorepository
# Children
# Samples
Storage
Transport
DNA, filter paper
206 707
206 707
RT
Regular mail
DNA, extracted
20 736
20 736
- 20 C
Dry ice
Serum
16 193
156 547
- 20/- 80 C
Dry ice
Plasma
13 344
114 278
- 70 C
Dry ice
PBMC
4 373
52 187
-135 C
Dry ice
Buffy coat
41 200
- 70 C
Dry ice
RNA
20 000
- 70 C
Dry ice
70 991
- 20/- 70 C
Regular mail
Stool
6 221
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
 Sent to analysis
 Stored at site
Samples/workday
Tubes sent/workday
Visits to DIPP clinic/year
IVGTT, OGTT/year
80,000
25,000
55,000
370
100
4,600
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)