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Genes are definitely involved in type 1 diabetes, but my view is that the genes do not cause type 1 diabetes, but allow the development of the disease. Then we have the beta cells, which are the target for the tissue destruction. And you may ask, ‘why the beta cells, why not the other cells in the pancreatic islets?’ And I don’t think there is any definite answer to that. Then some argue in favour of environmental factors and I think there are several factors supporting the idea that environmental factors are important. One is the rapid increase in incidence seen in many countries over the last 60 years. And then, we also know that when we look at HLA susceptibility in newly diagnosed patients, today you can progress to type 1 diabetes with less HLA susceptibility than 50 years ago, which indicates that the environmental pressure has increased over time. I think that there is agreement that autoreactive T-cells are behind the destruction of the insulin-producing beta cells and some argue that the regulatory T-cells are important from that point of view, that they can play down the autoreactive T-cells and, in that way, delay or prevent progression to clinical disease. Recent data suggests that the intestinal microbiome plays a role in the pathogenesis of the disease. And that is always linked to the role of the microbiome in the training of the immune system. Then we have the cytokines, which are secreted by the immune cells, and I think that cytokines are players in the destruction of the beta cells. Some people argue that B lymphoctyes are also involved in the disease process and there are some research findings supporting such a role. But on the other hand, we know that the autoantibodies produced by the beta cells do not play an active role in beta cell destruction.

Type 1 diabetes is an immune-mediated disease in which:

  • Genetic susceptibility is conferred by HLA and non-HLA genes
  • The disease process is triggered by an exogenous factor, most likely an infectious agent
  • Disease is driven by an exogenous antigen, potentially a dietary antigen
  • Disease is modified by a series of host-related and exogenous factors
  • Each phase of the process is affected by gene-gene and gene-environmental interactions