Abstract
Type 1 diabetes, formerly known as juvenile diabetes or insulin-dependent diabetes, results from the specific autoimmune destruction of the pancreatic islet beta cells. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. The disease may be diagnosed at any age but only in individuals who have certain HLA-DR-DQ-susceptibility haplotypes. Several non-HLA genetic factors either contribute to the genetic etiology or to the progression toward the clinical onset of the disease. Standardized tests for insulin autoantibodies (IAA) or GAD65 (GADA) have made it possible to demonstrate that the disease is triggered often during the first years of life. Environmental factors such as virus may be a triggering factor for IAA and GADA, which appear in a way that is associated with human leukocyte antigen (HLA). Individuals, who have developed IAA, GADA, or both, may develop yet other autoantibodies against IA-2 (IA-2A), ZnT8 transporter (ZnT8A), or both. Individuals with two or more islet autoantibodies will go on to develop type 1 diabetes (100%) but it may take 20years. The pathogenesis is likely to be controlled by CD8+ T cells recognizing autoantigen-peptides on HLA class I proteins expressed on the beta cell surface. The progression toward clinical onset is associated with a loss of beta cells, and the disease is predictable through HLA typing and test of IAA, GADA, IA-2A, and ZnT8A. Prevention and intervention trials are aiming to halt the beta cell-autoimmune process but the results of these trials have not altered the way in which to treat patients with type 1 diabetes.