Outstanding Scientific Achievement Award Lecture

Thirty Years of Investigating the Autoimmune Basis for Type 1 Diabetes: Why Can’t We Prevent This Disease?

Mark Atkinson, PhD

Reviewed by Joelle Escoffery, PhD

In 1974, the discovery of islet cell autoantibodies and the awareness that type 1 diabetes is an autoimmune disorder held great promise for the eventual cure of type 1 diabetes.  However, 30 years later, there are still numerous gaps in the understanding of type 1 diabetes.  First, the cause is still unknown.  In terms of the genetic contribution to type 1 diabetes, over 20 different loci have been shown to influence susceptibility. A variety of environmental influences, including viruses, immunization, breast feeding, and diet have been implicated. In terms of both genetic and environmental causes of diabetes, there are many candidates, but no obvious answer. The natural history of diabetes is also still unknown.  It is hypothesized that when an inciting event occurs in a person with genetic susceptibility, silent β-cell loss begins, eventually leading to overt type 1 diabetes. Along this progression, there are many factors that are unknown and many measurement obstacles to overcome. Further, there are no cost effective means of predicting type 1 diabetes, as the disease is sufficiently rare. Current cost estimates for type 1 screening range from $241 to $788 per child, totaling $72,300 for each case identified. Further, the ethics of screening for type 1 diabetes needs to be considered in the absence of available preventive therapy. Finally, prevention has suffered from the fact that available animal models are not easily translatable to humans.  In spite of the fact that there are 192 ways to cure type 1 diabetes in the NOD mouse, prevention in humans has remained elusive. Recommendation for the future include more coordinated and focused research efforts.  Other key issues that need to be addressed include whom to treat, what to treat with, when to treat, and who will pay for treatment.