Type 1 Diabetes and the β-Cell

Matthias von Herrath (La Jolla, CA) received the American Diabetes Association (ADA) 2008 Outstanding Scientific Achievement Award for his research on approaches to β-cell–specific immune interventions for type 1 diabetes. He began with a discussion of the evidence of a role of viral infections in the development of type 1 diabetes. In experimental models, viral infection may either accelerate or retard the immunologic process leading to type 1 diabetes. He pointed out that although type 1 diabetes is clearly an autoimmune disease, because a pancreas transplanted from an unaffected to a type 1 diabetic identical twin is associated with an immune response and rejection, the cause of autoreactivity is uncertain. Environmental factors are likely implicated: viral and also nutritional. Furthermore, the degree of islet inflammation in type 1 diabetes is rather mild, which may shed light on how viral infections might contribute to the disease process because only 3–4% of islets in pre-diabetic patients—and not a great deal more at the time of diagnosis—are affected by insulitis. Approaches to prevention might include modification of genes that predispose to diabetes and their gene products or modification of environmental factors, but emerging evidence suggests that type 1 diabetes is polygenic, with protective as well as enhancing genes, not all of which can suitably be altered.

Curing type 1 diabetes might be accomplished with an unlimited β-cell source, perhaps from stem cells, to make islet transplantation more generally feasible. β-Cell augmentation may be an intermediate goal for which islet transplant protocols not flawed by loss of islets after 3–4 years must be developed, perhaps by eliminating preexisting autoaggressive T-cells. Ongoing trials to prevent and cure recent-onset …