DIABETES AND THE ENDOCRINE PANCREAS I: Edited by David M. HarlanRevisiting the notion of type 1 diabetes being a T-cell-mediated autoimmune diseaseSkog, Oskar; Korsgren, Stella; Melhus, Åsa; Korsgren, OlleAuthor Information aDepartment of Immunology, Genetics and Pathology bDepartment of Medical Sciences, Section of Clinical Microbiology, Uppsala University, Uppsala, Sweden Correspondence to Olle Korsgren, IGP, Rudbeck Laboratory C11, Uppsala University, 751 85 Uppsala, Sweden. Tel: +46 18 611 00 00; e-mail: [email protected] Current Opinion in Endocrinology & Diabetes and Obesity: April 2013 - Volume 20 - Issue 2 - p 118-123 doi: 10.1097/MED.0b013e32835edb89 Buy Metrics Abstract Purpose of review Type 1 diabetes (T1D) research is at present in a critical period of development and during the past few years several large phase III studies targeting T-cell autoimmunity in recent-onset patients with T1D failed to reach the primary endpoint. Recent findings Cause and pathogenesis of T1D remain largely unknown. In humans, insulitis is discrete, affects few islets and is present only in about one-third of patients with recent-onset T1D. The rapid increase in incidence of T1D argues against a decisive role for genetic factors and instead for the hypothesis that infectious agents, possibly entering the pancreas via the ductal compartment, are involved in disease pathogenesis. Repeated episodes of bacteria or virus-induced innate inflammations affecting only certain lobes of the pancreas fit well with the reported heterogeneity of the disease within the pancreas as well as with the slow progression over many years. Summary In humans there is limited support for T1D being primarily an autoimmune disease; instead available findings support the view that T1D can be regarded as an innate inflammatory disease affecting the entire pancreas, but with its main clinical manifestations emanating from the loss of the insulin-producing cells. Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.