Research
Screening, genetics and immunology as tools to develop therapies for prevention and intervention
DiaUnion’s vision is to create a center of excellence for research into autoimmune diabetes (type 1 diabetes, T1D), and related autoimmune diseases. These diseases are incurable today, and DiaUnion’s long-term goal is to develop therapies for prevention and intervention to cure these diseases.
T1D research in DiaUnion takes a novel approach through collaboration with two related autoimmune diseases, celiac disease (CD) and autoimmune thyroiditis (AIT). The three diseases share HLA risk genes, leading to overlap in the prevalence of the diseases as shown in the figure below. CD affects 10% and AIT up to 30% of all children with type 1 diabetes. The link between T1D and related autoimmune diseases holds a huge, and only to a lesser extent cultivated, potential for the development of new drugs and therapies.
Prevention of T1D involves treatment to prevent the disease from developing. A distinction is made between primary, secondary and tertiary prevention:
In primary prevention, a treatment is performed before the immune system is activated, based solely on the person’s genetic risk measured through a blood test. Thus, there are no visible or measurable signs of disease at all. In T1D, this corresponds in the diagram of the disease development to the stage before the start of T1D. The treatment can be imagined as e.g. a vaccine, injection or tablet treatment.
In secondary prevention, a treatment is performed when there are measurable signs of disease but no symptoms yet. In T1D, this corresponds to steps 1 and 2 in the diagram for the development of the disease, and the markers for whether one is in the increased risk group are the development of autoantibodies, which can be measured through a blood test. The treatment can be imagined as e.g. a vaccine, injection or tablet treatment.
In tertiary prevention, treatment is performed after symptoms have occurred and the disease has been diagnosed. In T1D, this corresponds to the course from step 3 onwards in the diagram for disease development. The symptom treatment is the various forms of insulin treatment offered in T1D, while an actual treatment that stops the immune system’s attack on the beta cells, as in primary and secondary prevention, can be imagined as e.g. a vaccine, injection or tablet treatment.
The earlier it is possible to intervene, the better, so that the impact of the disease is minimized, which is why primary prevention as early in life as possible would be preferable. However, as effective therapies for prevention and intervention in T1D have not yet been developed, and in order to help everyone, intervention at all stages of disease development is being researched.
In order to research and, in the long term, perform preventive treatments, the people who are at risk of developing T1D must be found through screening of blood samples.
In primary prevention, all newborns will need to be screened for genetic T1D predisposition, which requires only a single blood test at birth.
In secondary prevention, screening for autoantibodies is done, which for genetically predisposed can develop at any time in life, in T1D, however most often in the young years. If genetic predisposition has not been screened, it is in principle necessary for everyone to have blood samples taken at regular intervals, but in practice, close relatives to people with T1D are typically screened in an age group where the risk of developing T1D is greatest.
DiaUnion 1.0
Identification of new biomarkers in T1D – 2 projects
The aim of the two research projects is to evaluate whether molecular lipid species can more accurately predict the risk of, as well as time, future development of T1D. The project will link to CD and compare lipidomics in the two diseases.
Cohorts collected at Lund University CRC in Malmö will be used to identify children at high risk, at different stages in the pathogenic process.
Blood samples will be made available for lipidomics and cellular flow cytometric analyzes at Steno Diabetes Center Copenhagen, and models will be developed to predict the rate of progression to T1D, as well as identify the optimal age for performing lipidomic screening for T1D risk.
Preliminary study of interregional public screening program
The goal is to establish a demonstration project for 2,000 children in the Capital Region of Denmark and 2,000 children in Region Skåne to show that it is possible to screen for biomarkers for T1D, CD and AIT, three diseases that share the association with HLA-DR and DQ risk haplotypes.
The rationale is to identify the healthy children who will later in life develop one or more of the three diseases and offer them:
- Early diagnosis to prevent serious and life-threatening disease complications.
- Psychosocial support in preparation for dealing with the disease when the diagnosis is made without symptoms.
- Participation in clinical prevention trials.
DiaUnion 2.0
Based on the activities of DiaUnion 1.0, the next step in DiaUnion 2.0 is to establish a public screening program as a basis for advanced prevention and intervention studies.
DiaUnion 2.0 is under planning
