Pathogenesis of fulminant type 1 diabetes: Genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research.

We reviewed fulminant type 1 diabetes, a recently established subtype of type 1 diabetes, from the aspects of genes, viruses, immune mechanism and usefulness of patient-derived induced pluripotent stem cells (iPSCs). In an analysis of the pancreas of patients with fulminant type 1 diabetes, viral antigens and viral receptors were expressed in β-cells, as well as macrophages and T lymphocytes surrounding the β-cells. These findings suggest that the β-cells of patients with fulminant type 1 diabetes are destroyed during an immune response against viral infection of the pancreas. Recently, fulminant type 1 diabetes was induced by treatment with anti-programmed cell death 1 antibodies, suggesting that immune regulatory mechanisms are also involved in the onset of this disease. We generated iPSCs from patients with fulminant type 1 diabetes for the first time. We also successfully differentiated patient-derived iPSCs into insulin-producing cells in vitro, and produced a disease model. The proportion of cytokine-induced apoptotic cells among insulin-positive cells was higher in the iPSCs from patients with fulminant type 1 diabetes than in iPSCs from healthy control participants. We carried out ribonucleic acid sequencing in insulin-producing cells differentiated from patient-derived iPSCs, and are now attempting to identify new biomarkers for the disease.