Understanding the Immunology of Type 1 Diabetes – An Overview of Current Knowledge and Perspectives for the Future

Abstract

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. 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. 17The 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 AbstractType 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.

Diabetes inside and outside of the body: a psycho-anthropological analysis of the treatment of "sugar disease" in Cameroon

“…This constitutional predisposition results in a congenital weakness of the endocrine pancreas, more vulnerable to pathogens like viruses as in the case of type 1B diabetes, 14 or prone to the development of immunological processes as is the case for type 1A diabetes. 15 In addition, the pancreas, when subjected to considerable activity, inevitably goes beyond its capacity and becomes exhausted. As a result, in individuals whose endocrine function of the pancreas is already congenitally weak or at the limits of its sufficiency, diabetes can easily occur.…”