Autoantibodies in type 1 diabetes.
Diabetes mellitus is a disorder characterized by hyperglycemia in both the fasting and post-prandial states. The two most common forms of diabetes mellitus, type 1 and type 2 (previously called juvenile-onset and adult-onset, respectively), comprise the vast majority of cases. Type 1 diabetes (T1DM) has been shown to be a disease characterized by immune-mediated destruction of the insulin-secreting cells of the pancreas; it comprises the majority of cases of diabetes seen in childhood and approximately, 5-10% of all cases of diabetes mellitus in the USA and perhaps accounts for an even higher percentage in those nations with lower rates of obesity. The process of beta-cell destruction, marked by the production of autoantibodies to the beta-cell, occurs over many years and ultimately results in metabolic abnormalities first manifested as impaired glucose tolerance and then progressing to symptomatic hyperglycemia. It has been reported that approximately 50% of the genetic risk for T1DM can be attributed to the HLA region. The highest risk HLA-DR3/4 DQ8 genotype has been shown to be highly associated with beta-cell autoimmunity. The first antibodies described in association with the development of T1DM were islet cell autoantibodies (ICA). Subsequently, antibodies to insulin (IAA), glutamic acid decarboxylase (GAA or GAD) and protein tyrosine phosphatase (IA2 or ICA512) have all been defined. The number of antibodies, rather than the individual antibody, is thought to be most predictive of progression to overt diabetes.
Taplin
Craig E
CE
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045-6511, USA.
Barker
Jennifer M
JM
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006683:HLA-DQ Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice
D001323:Autoantibodies; D001324:Autoantigens; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen