Genetics, pathogenesis and clinical interventions in type 1 diabetes

Abstract

The clinical picture of type 1 diabetes — a progressive loss of pancreatic β-cell function and a requirement for daily insulin treatment — has been apparent for over a century but the precise nature of the disease progression continues to emerge. Recent progress towards understanding the pathogenetics and genetics of diabetes has been rapid, thanks to extensive research in rodent models and in diabetes patients. A review by Jeffrey Bluestone, Kevan Herold and George Eisenbarth recaps some of the major developments of the past decade and reports on the exciting new clinical interventions that are now being tested, some with the potential to be adapted for use in autoimmune diseases other than diabetes. 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.