Type 1 diabetes: pathogenesis and prevention

Abstract

Type 1 diabetes results from the autoimmune destruction of insulin-producing β cells in the pancreas. Genetic and, as yet undefined, environmental factors act together to precipitate the disease. The excess mortality associated with the complications of type 1 diabetes and the increasing incidence of childhood type 1 diabetes emphasize the importance of therapeutic strategies to prevent this chronic disorder. Why is it considered that type 1 diabetes might be preventable? Different strands of diabetes research are coming together to suggest therapeutic targets. Islet cell autoantibody assays make it possible to accurately identify people at risk of future disease. In most cases, a long prodrome provides a window of opportunity to reverse the autoimmune process. Although no current “cure” exists, recent genetic data and preliminary trial results suggest T cells as a target for preventive strategies. Another potentially attainable target is induction of tolerance to the β-cell proteins such as insulin that are inappropriately recognized. Other strategies involve β-cell replacement, but currently there are insufficient donor cells available. This may be overcome as the processes controlling the differentiation of pancreatic and nonpancreatic progenitors as well as replication of existing islet β cells are unravelled.