Thirty Years of Investigating the Autoimmune Basis for Type 1 Diabetes

Why Can't We Prevent or Reverse This Disease?

Mark A. Atkinson


Diabetes. 2005;54(5):1253-1263. 

In This Article

Abstract and Introduction

Thirty years ago, a convergence of investigational observations lead to the now widely accepted notion that type 1 diabetes results from an autoimmune destruction of insulin-producing β-cells in subjects genetically predisposed to the disease. Improvements in understand-ing of the natural history of type 1 diabetes, the biochemical identification of autoantigens, the discovery of spontaneous animal models for the disease, the availability of immune-modulating agents, and other important facets, including disease prediction, drove an early sense of optimism that the prevention of type 1 diabetes was possible and, in some research circles, that ability was thought to be within a not-to-distant reach. Unfortunately, those early expectations proved overly optimistic, and despite the aforementioned knowledge gains, the generation of improved investigational tools, the identification of methods to prevent the disease in animal models, and the formation of very large disease prevention trials, a means to prevent type 1 diabetes in humans continues to remain elusive. Believing in the concept of "informative failures" (a.k.a., wise people learn from their mistakes), this lecture reviews the knowledge base collected over this time period and, when combined with an analysis of those research experiences, sets forth a proposal for future investigations that will, hopefully, turn discoveries into a means for the prevention or reversal of type 1 diabetes.

I'll begin this lecture the same way that I will end it: by conveying a heartfelt word of thanks to the many people who deserve recognition on my acceptance of this award, as well as to recognize those who have contributed to the science that stands behind it. At the end of the talk, I will recognize a few of these special people. But for now, thanks are extended to my colleagues who selected me for this year's award. A great deal of thanks is also extended to the American Diabetes Association (ADA) for the impact of this organization on my entire career. The ADA has always been there for me, for us who care about diabetes, and for those with the disease. Upon hearing of my receipt of this award, I was advised that the best award lectures of the past have told a story. So, in taking that advice, today I will tell a story; but, if it were to be bound into a book, it would not easily fit into a particular subject category on the shelf at your local bookstore. Parts of the story would suggest that it belongs in the history section, yet in other ways, this story would be a drama, a comedy, a tragedy, a lesson on geography, a primer on public health and nutrition, and, perhaps most of all, an unsolved mystery.


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