Type 1 diabetes risk

Research team members

Nicolai Andre Blix-Lund, Benedicte  Jørgenrud, and Kjersti Skjold Rønningen.


Type 1 diabetes risk in children, the MIDIA study


Type 1 diabetes risk in children, the MIDIA study

Type 1 diabetes (T1D) is after asthma the disease with the highest prevalence in childhood. The incidence has increase with 5% per year in Europe during the last years, and Norway is found on the top.  TID is caused by a combination of genetic and environmental factors. T1D results from autoimmune destruction of the insulin-producing betacells in the pancreas, after a sub-clinical period of variable length (months to years) where autoantibodies can be detected in peripheral blood.  The MIDIA (a Norwegian acronym for Environmental Triggers of Type 1 Diabetes) study recruited newborns from the general population with the highest genetic risk for developing Type 1 Diabetes (T1D); those carrying the HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*05-DQB1*02 genotype, and follows them with monthly stool samples the first 3 years of life, blood samples and questionnaires at 3, 6, 9 and 12 months of age and thereafter annually up to 15 years. The high-risk HLA genotype is present in 2.1% of Norwegian newborns and confers a calculated 7% risk for getting T1D before 15 years of age and a life time risk of 20%. Inclusion of only the high-risk genotype makes the cohort exceptionally homogeneous while identifying about 30% of future cases of T1D. It started in small scale in the summer of 2001, and gradually spread, covering the whole country of Norway from March 2006. All recruitment to MIDIA was stopped effectively from December 10, 2007 due to problems with previously issued approvals. A legal opinion emerged that screening was against the Norwegian Biotechnology law of 1994, which prohibits genotyping children younger than 16 years of age for those medical conditions where no effective clinical treatment can be offered. Altogether, 48,000 children were recruited to MIDIA. 1047 were identified to carry of whom 96.8% took part in the follow-up, and about 95% of scheduled blood samples, stool samples and questionnaires have been received.
At the end of March 2013, 29 of MIDIA children have got T1D, 41 are confirmed positive for two or three autoantibodies and 30 for one autoantibody, www.fhi.no/midia. Children with confirmed autoimmunity/T1D are available for nested case-controls studies to identify the trigger(s) of T1D. The MIDIA cohort has a large overlap with the Norwegian Mother and Child Cohort study (MoBa): approximately 50% of the participants in MIDIA have mothers who have consented for usage of their pregnancy samples and questionnaires in MIDIA. Questionnaires have been asked for at 17th, 22nd and 30th week of pregnancy, when the child is 6 and 18 months, and at 3, 5, 7, 10 and 12 years of age. Blood samples were asked for at 17th week of pregnancy and at the time of delivery from the mother and cord blood was taken from the baby, www.fhi.no/morogbarn.

 

Current research projects on MIDIA at Department of Pediatric Research

 

Diet and the risk of developing islet autoimmunity and type 1 diabetes

 

Background

There have recently been a noticeable increase in the incidence of T1D, and since the genetic background is stable this must result from environmental factors. Diet as an important environmental source of exposure may contribute significantly to the development of T1D, but little evidence for this is available from prospective studies in humans.

 

Research goals and strategy

Our objective is to study the relationship between the mother's and children's diet and development of autoimmunity and T1D in genetically susceptible children. Our main hypothesis is that there are dietary factors triggering development of autoimmunity and type 1 diabetes. This may be factors initiating the process already in foetal life or in early childhood.

 

Approaches

  • To investigate the relationship between exclusive and total breast-feeding and the risk of islet autoimmunity and T1D in children.
  • To investigate whether a higher total level of long-chain omega-3 fatty acid or marine omega-3 fatty acids (e.g. DHA, EPA) status of the mother during pregnancy and of the child is associated with a protective effect for islet autoimmunity and T1D.
  • To investigate whether lower level of 25-hydroxyvitamin D (indicator of vitamin D status) in the mother during pregnancy and in the child is associated with higher risk of islet autoimmunity and T1D.


The ealiest prediction of islet autoimmunity and Type 1 Diabetes (T1D) in the Norwegian MIDIA Study


Background

T1D is caused by a combination of genetic and environmental factors. However, it is still not known what starts the disease process, and it is not possible to prevent the disease. Identification of novel markers with increased specificity/sensitivity is urgently needed, and longitudinal studies are necessary in this endeavor. Recently Finish children with genetic risk for T1D, participating in The Diabetes Prediction and Prevention Study, were studied by new markers (Metabolomics and lipidomics). It was possible to show dysregulation of lipid and amino acid metabolism proceeding islet autoimmunity in children who later progressed to T1D. These exciting new findings are, however, needed to be studied in another prospective birth cohort. In The MIDIA study, babies with the high-risk HLA genotype have been identified and are followed with blood and stool samples as well as questionnaires. In collaboration with The Quantitative Biology and Information group, VVT, Technical Research Center of Finland, we will study metabolomic dysregulation and search for new markers. The aim is to offer new opportunities for disease prediction and early prevention.

 

Research goals and strategy

To identify biomarkers for earlier prediction of Type 1 Diabetes (T1D) than what is possible today, and to increase our understanding of the aetiology of human islet autoimmunity and T1D.


Approaches

  • To investigate the metabolomics in plasma samples preceding autoimmunity in cases from the MIDIA study and age matched control.
  • To identify new metabolomic markers in predicting T1D
  • To investigate metabolomic markers responsible for progression form autoimmunity to T1D


Main national and international collaborators

The MIDIA research group (Elisabet Witsø, German Tapia, Håkon Bøås, Kaja Klykken Aas, Trond Rasmussen, Lars Christian Stene), Norwegian Institute of Public Health, Oslo.

Jens Petter Berg, Oslo University Hospital, Ullevål, Oslo

Milaim Pepay,  Oslo University Hospital, Aker, Oslo

Eric de Muinch, CEES, Faculty of Mathematics and Natural Science, University of Oslo, Oslo.

Nils Christian Stenseth, CEES, Faculty of Mathematics and Natural Science, University of Oslo, Oslo.

Knut Rudi, Department of Chemistry, Biotechnology and Food Science, University of Life Sciences, Ås, Norway

Ondrej Cinek, 2. Deptartment of Pediatrics, Motol University Hospital, Prague, The Czech Republic, 

Heikki Hyöty, Dept. of Microbiology, University of Tampere, Finland.

Sami Oikarinen, Dept. of Microbiology, University of Tampere, Finland.

Flemming Pociot, Steno Hospital and Research Centre, Copenhagen, Denmark.

Matej Oresic, VVT Technical Research Institute, Helsinki, Finland.

 

Financial support

ExtraStiftelsen (The Norwegian Organization for Health and Rehabilitation)

The Norwegian Research Council

 

Selected publications


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