Get Adobe Flash player
Diabetes Immunology Understanding the Immunology of Type 1 Diabetes – An Overview of Current Knowledge and Perspectives for the Future Anil Piya 1 and Aaron W Michels 2 1. Pediatric Endocrinology Fellow; 2. Assistant Professor of Pediatrics and Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, US Abstract Type 1 diabetes is a chronic autoimmune disease resulting from the immune destruction of insulin-producing β-cells in pancreatic islets. It is now a predicable disease in humans with the measurement of islet autoantibodies. Despite the ability to assess disease risk, there is no cure for type 1 diabetes and treatment requires lifelong insulin administration. Individuals with type 1 diabetes are at risk of long-term complications of the disease and the development of concomitant autoimmune disorders. Our understanding of the immunology of diabetes has increased greatly over the last decade at a basic science level, with translation to type 1 diabetes patients. Therapies are emerging to prevent beta cell destruction in these patients. This article centres around our current understanding of the immunology of type 1 diabetes, with a focus on immune intervention for the prevention and ultimate cure of the disease. Keywords Type 1 diabetes, autoimmunity, immunology, immune therapies, autoantibodies, T cells, antigen presentation Disclosure: The authors have no conflict of interests to declare. Acknowledgements: Aaron W Michels receives research support from the National Institutes of Health (DK09599 and AI050864), Juvenile Diabetes Research Foundation, and Children’s Diabetes Foundation. Received: 15 June 2012 Accepted: 28 June 2012 Citation: European Endocrinology, 2012;8(2):70–4 Correspondence: Aaron W Michels, Assistant Professor of Pediatrics and Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Court, MS A140, Aurora, CO 80045, US. E: Aaron.Michels@ucdenver.edu Type 1 diabetes is classified into two types by the American Diabetes Association; type 1A diabetes is the immune-mediated form and type 1B the non–immune mediated form of the disease, both leading to β-cell destruction and absolute insulin deficiency. It is estimated that approximately 1.5 million people in the US have type 1A diabetes. The incidence of type 1 diabetes is increasing worldwide at a rate of 3–5 % each year. Strikingly, it has doubled in each of the last two decades, children less than five years of age being the most commonly affected group. 1,2 Recently, it has been reported that if the present trends continue, the number of patients younger than five years of age will have risen by 70 % by the year 2020. 3 The increasing incidence of type 1 diabetes is unlikely due to genes, as the increase has occurred over a relatively short period of time. Environmental causes have been hypothesised to increase the incidence of diabetes. 4,5 A number of associations are reported between an environmental stimulus and diabetes incidence, including age of gluten exposure, introduction of infant formulas to the diet and type of these formulas, change in gut microbial flora, vitamin D deficiency, viral infections, and others. 6–11 Alternatively, an unknown protective element in the environment may have been removed 20–30 years ago. There are a number of large prospective studies under way to identify environmental determinants of type 1 diabetes, including The environmental determinants of diabetes in the young (TEDDY) study 12 and the MIDIA (Norwegian acronym for ‘environmental triggers of type 1 diabetes’) study in Norway. 13 70 Genetics Type 1A diabetes is a polygenic disorder and much is known about the genetics associated with it. Approximately 1/300 individuals from the general population develop type 1 diabetes while 1/20 siblings of patients with type 1 diabetes develop the disorder. 14–16 It was previously thought that the concordance rate for monozygotic twins with type 1 diabetes was relatively low (<50  %); however, following a cohort of monozygotic twins for longer than 50 years, the concordance rate for type 1 diabetes development is 66  %. A recent analysis of these long-term twin data indicates that there is no age at which an initially discordant monozygotic twin is no longer at risk, with some developing type 1 diabetes in the fourth and fifth decades of life. 17 The major genetic determinant of type 1 diabetes is conferred by genes in the human leukocyte antigen (HLA) complex, which is divided into three regions: class I, II, and III. Alleles of the class II genes, DQ and DR (and to a lesser extent DP), are the most important determinants of type 1 diabetes. These major histocompatibility complex (MHC) class II molecules are expressed on antigen-presenting cells (macrophages, dendritic cells, and B  cells) and present antigens to CD4+ T lymphocytes. DQ2 and DQ8 alleles are strongly associated with type 1 diabetes and more than 90  % of people with type 1A diabetes possess one or both of these genes, compared with 40  % of the US population in general. 18 © TOUCH MEDICAL MEDIA 2012