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Genetics, pathogenesis and clinical interventions in type 1 diabetes

Abstract

Type 1 diabetes is an autoimmune disorder afflicting millions of people worldwide. Once diagnosed, patients require lifelong insulin treatment and can experience numerous disease-associated complications. The last decade has seen tremendous advances in elucidating the causes and treatment of the disease based on extensive research both in rodent models of spontaneous diabetes and in humans. Integrating these advances has led to the recognition that the balance between regulatory and effector T cells determines disease risk, timing of disease activation, and disease tempo. Here we describe current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies.

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Figure 1: Markers of diabetes.
Figure 2: Immunologic history of type 1 diabetes.
Figure 3: Immune system balance is key to disease pathogenesis.
Figure 4: Targets of immune intervention in type 1 diabetes.

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Acknowledgements

We thank the many people in our laboratories and the community who have made significant contributions to the research highlighted in this review. We owe special thanks to L. Lanier, M. Anderson and M. Atkinson as well as the members of the Brehm Coalition for many discussions and critiques of the manuscript. Additionally, we thank J. Matthews for putting together Fig. 4. We acknowledge support from NIAID, NIDDK, JDRF, CDF and the Brehm Coalition.

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Each co-author (G.E., K.H. and J.A.B.) contributed experimental results, data analysis, writing and creative contributions to this work.

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Correspondence to Jeffrey A. Bluestone.

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J.A.B. has a financial interest in the commercialization of the anti-CD3 monoclonal antibody. Both J.A.B. and G.E. serve on several boards involved in the development of drugs to treat type 1 diabetes.

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Bluestone, J., Herold, K. & Eisenbarth, G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464, 1293–1300 (2010). https://doi.org/10.1038/nature08933

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