The susceptibility to type 1 diabetes is determined by a combination of genetic and environmental factors. Globally the incidence of type 1 diabetes is highest in Finland (around 60 new cases/100 000 children under the age of 15 years annually). The number of new cases with type 1 diabetes among European children younger than five years of age has been predicted to double between 2005 and 2020. The etiology is largely unknown; no efficient primary prevention is available. Deeper insights are needed into the process resulting in clinical disease to be able to develop effective preventive measures.
Type 1 diabetes is an autoimmune disease characterized by targeted destruction of the insulin-producing beta cells within the pancreatic islets. Although the precise etiology remains unclear, the pathogenesis of the disease is thought to involve T-cell mediated destruction of the betacells. The clinical diagnosis of type 1 diabetes is preceded by an asymptomatic preclinical stage, which can last from a few months to more than 20 years, during which autoantibodies against beta-cell autoantigens appear into the peripheral circulation. Diabetes-associated autoantibodies represent the first detectable sign of the initiation of the disease process, and the number of autoantibodies correlates with the probability of disease progression.
According to the hygiene hypothesis, early exposure to specific microbes in infancy is beneficial for the maturation of the immune system. The gut microbiota has a significant role in the early education of the immune system, and a diverse, stable microbiota has been shown to support health. Both in the DIABIMMUNE and the DIPP studies it has been shown that the appearance of autoantibodies is accompanied by a decrease in the microbial diversity, while microbial species and metabolites associated with inflammatory processes are increased (Kostic AD et al. Cell Host Microbiome 2015; Giongo A et al. ISME J 2011). These observations imply that the gut microbiota may play an important role in the progression from autoantibody positivity to clinical disease. Whether the pre-diabetic disease process could be delayed or even prevented by modulating the gut microbiota in individuals at increased risk for type 1 diabetes remains to be assessed in further studies.
Type 1 diabetes is an immune-mediated disease, in which the insulin producing pancreatic beta cells are destroyed by the body’s own immune cells. Up-regulation of interferon-gamma secreting Th1 cells and phenotypic instability of activated Th17 cells as well as impaired activation and function of regulatory T cells have been associated with preclinical and clinical type 1 diabetes. Cells of the innate immune system, such as dendritic cells, are important regulators of T-cell activation, differentiation and function, and therefore they are likely to contribute in immune dysregulation leading to the breakage of self-tolerance. Our aim is gaining a comprehensive view on immunological mechanisms causing the loss of functional beta cells and how environmental cues are translated into dysregulated immune reactions. The goal is to develop new tools for improved diagnostics and novel therapeutic approaches for type 1 diabetes and to find out whether adverse immune processes could be reversed or inhibited by pharmacological or other means.