Immunology of type 1 diabetes

Abstract

The incidence of type 1 diabetes in the UK is 20 per 100 000 and increasing, particularly in the under-5-years age group.1 It comes with the burden of daily insulin injection and blood testing, as well as both short- and long-term complications, and this can include premature death. The standardized mortality ratio for type 1 diabetes has been estimated as 4-fold for females and 2.7-fold for males in the UK.2 Even with tight glucose control, there is a significant risk of neuropathy, retinopathy and nephropathy, as well as a 3-fold increase in the risk of severe hypoglycaemia.3 Understanding the pathology of type 1 diabetes may help improve management. Type 1 diabetes is characterized by an absolute loss of insulin secretion, and results from an autoimmune process that destroys insulin-producing β cells within the pancreatic islet. This review will focus on the immunology of type 1 diabetes, and how this understanding may influence the clinical management, and development of new treatments for this disease. There are over one million islets in a healthy adult pancreas. They make up 1% of the total pancreatic volume, weigh about 1 g, and contain about 1 mg of insulin.4 Histological analysis of the pancreas from patients with type 1 diabetes shows immunological activity not present in a healthy or a type 2 diabetic pancreas.5 This activity is limited to insulin-containing islets, includes infiltration by activated lymphocytes, antibodies and components of the complement system. These histological findings are consistent with type 1 diabetes being an immune-mediated disease (Figure 1). Figure 1. Insulitis. A pancreatic islet (insulin in red) being invaded by T lymphocytes (green), the currently irreversible process that leads to type 1 diabetes. Courtesy of Anne Cooke, University of Cambridge. Further evidence comes from studies showing that drugs that suppress the immune response can modulate … Address correspondence to: Dr P. Narendran, Clinical Science at North Bristol, University of Bristol, Southmead Hospital, Bristol BS10 5NB. email: parth.narendran{at}bristol.ac.uk