- To determine whether geographical variation in type 1 diabetes incidence across Europe reflects differences in prevalence of genes confirming susceptibility or protection to the disease.
- To establish whether the pattern of autoantibodies in newly diagnosed patients with type 1 diabetes varies across Europe, and if so, whether this is related to differences in the prevalence of genes confirming susceptibility to the disease.
- To estimate the absolute risk of type 1 diabetes associated with markers of genetic susceptibility and immune markers of risk in European populations with different background risk of the disease.
- To determine whether there is heterogeneity in genotype and autoantibodies according to age at diagnosis.
- To investigate the aetiological role of a potential non-genetic determinant, namely Coxsackie B virus infection, with particular attention to the associations between Coxsackie B virus antibodies, islet autoantibodies at diagnosis and genotype.
EURODIAB ACE, an ongoing Concerted Action, has demonstrated a more than 10-fold difference in the risk of type 1 diabetes across Europe, implying that Europe represents a unique setting for research into the aetiology of type 1 diabetes. The existing registration network of new (incident) cases of type 1 diabetes will provide the prospective epidemiological sampling framework of probands and their families for intensive genetic and immune markers. The network comprises 44 centres from 28 European nations, covering 25-30% of all European children and producing about 2800 new cases of childhood-onset type 1 diabetes annually. In addition, some 1350 new cases with onset in the age group 15-29 years will be registered annually from 12 centres. From selected centres, characterized by different levels of population risk of type 1 diabetes, about 2000 cases and their nuclear family members, totalling about 8000 individuals, will be sampled for detailed investigations. Leading expert laboratories in advanced molecular genetics and immunology will provide laboratory support, organized in the new Concerted Action, PARADIGM.