Type 1 diabetes mellitus (T1DM) develops in genetically susceptible individuals. There is a strong disease association with environmental factors, which are thought to trigger the disease. The disease pathogenesis is dependent on autoimmune phenomena involving both the cellular and humoral immune response direct against several autoantigens in the beta cells. The disease has a long prodrome and the appearance of GAD65, IA-2 or insulin autoantibodies predict disease. In the present study - Diabetes Prediction in Skane (DiPiS) we will screen all newborns (about 10, 000 children per year) for high risk HLA and other TIDM genetic factors. Islet cell autoantibodies against GAD65, IA-2 and insulin will be analyzed at birth and during follow-up to identify environmental triggers. In particular, we will test the hypothesis that gestational adverse events represents triggers of islet autoimmunity that will progress to type 1 diabetes but only in some susceptible subjects.
The Specific aims are: 1) to screen all newborn babies in Skane, the southern region of Sweden with 1.2 million inhabitants; 2) to analyze the cord blood for type 1 diabetes high risk HLA alleles and for the three islet cell autoantibodies, GAD65Ab, IAA and IA-2Ab; 3) to analyze infectious history, gestational adverse events and psychosocial factors as additive or potentiating factors to type 1 diabetes risk along with virus PCR and serology during pregnancy; 4) to define isotype, subtype and epitope specificities of autoantibodies to GAD65, IA-2 and insulin at birth, at the first appearance of autoantibodies and at diagnosis of type 1 diabetes; 5) to determine autoantigen reactive T cells in neonates born to healthy mothers positive for autoantibodies as evidence of autoimmunity exposure and 6) to submit critical data to the Data Coordinating Center (DCC) to effectively identify environmental triggers of type 1 diabetes. The long-term objective is to identify the role of gestational infections or other adverse events and psychological factors that increase the risk for type 1 diabetes in genetically susceptible children. Understanding the interaction between genetic risk and environmental risk factors may permit the development of strategies to reduced exposure and thereby minimize diabetes risk.
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