Genetic Testing of Newborns for Type 1 Diabetes Susceptibility – The MIDIA Study

1.1 Background and status of knowledge Type 1 Diabetes (T1D) is a T-cell mediated autoimmune disease that develops in genetically susceptible individuals whose immune system destroys the majority of insulin-secreting βcells in pancreatic islets (Eizirik et al., 2009). The incidence of T1D has increased more than twoto threefold over the past half century, the most striking example being Finland where it has risen from 12 to 63/100,000 (Knip & Siljander, 2008; Patterson et al., 2009). This increase in incidence has not been paralleled by an increase in the frequency of major risk genes, including HLA class II, insulin, PTPN22, CTLA-4 and IL2RA (Barrett et al., 2009). Indeed, the prevalence of the classical HLA class II genes, which account for approximately 40% of genetic risk, appears to be decreasing (Gillespie et al., 2004; Fourlanos et al., 2008). There are now more than 40 risk loci associated with T1D with the majority of non-HLA genes displaying odds ratio <1.2. (Barrett et al., 2009). Moreover, most individuals who possess T1D risk genes do not develop the disease. Importantly, the concordance rate among monozygotic twins ranges from as low as 25 to 65% (Redendo et al., 1999, 2008; Hyttinen et al., 2003) and is approximately 6% in siblings. A common explanation has been that changes in environment must contribute to the increase in the disease. In particular, environmental exposures to dietary antigens and microbes have been implicated (Knip et al., 2005; Lefebvre et al., 2006). However, no single pathogenic environmental agent has been identified that explain all cases. In all likelihood, T1D develops by various combinations of pathways in response to commonly encountered environmental exposures.