Type 1 diabetes

Type 1 diabetes is due to destruction of B-cells in the pancreatic islets of Langerhans with resulting loss of insulin production. A combination of environmental and genetic factors that trigger an autoimmune attack on the B-cells is responsible, occurring in genetically susceptible individuals. Thus, among monozygotic identical twins only about one-third of the pairs are concordant for diabetes in contrast to the situation in Type 2 diabetes where almost all pairs are concordant. The process of islet destruction probably begins very early in life and is known to start several years before the clinical onset of diabetes.

HLA status

The major histocompatibility complex antigens are adjuncts to several types of immunological activity. Ninety percent of Type 1 diabetic patients show either DR3 or DR4, or both together, while DR2 is protective against diabetes.

Autoantibodies and cellular immunity

Islet cell antibodies are present at diagnosis in most Type 1 diabetic patients and gradually decline and disappear during the following years. Antibodies to specific proteins have more recently been identified: these include antibodies to glutamic acid decarboxylase (GAD, a 64-kDa antigen); and even closer association is found in the presence of antibodies to tyrosine phosphatase (37 kDa, IA-2). The presence in a non-diabetic individual of three or more antibodies (islet cell antibodies, anti-GAD antibodies, anti-IA-2 antibodies, anti-insulin autoantibodies) indicates an 88% chance of developing diabetes within 10 years.

The presence of insulinitis at the onset of Type 1 diabetes represents the role of inflammatory cells (for example, cytotoxic T cells and macrophages) in B-cell destruction. Macrophages also produce cytokines leading to activation of lymphocytes known to be present at the onset of Type 1 diabetes.

Attempts have been made to prevent the onset of Type 1 diabetes. Immune suppression can to some extent preserve islet function, but permanent remissions are not normally achieved and the treatment is in any case too dangerous for routine use.

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