Insulin Autoantibodies (IAA)

Overview:

Type 1 diabetes, commonly referred to as insulin-dependent diabetes (IDDM), is caused by pancreatic beta-cell destruction that leads to an absolute insulin deficiency.1 The clinical onset of diabetes does not occur until 80% to 90% of these cells have been destroyed. Prior to clinical onset, type 1 diabetes is often characterized by circulating autoantibodies against a variety of islet cell antigens, including glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2), and insulin.2-5 The autoimmune destruction of the insulin-producing pancreatic beta cells is thought to be the primary cause of type 1 diabetes. The presence of these autoantibodies provides early evidence of autoimmune disease activity, and their measurement can be useful in assisting the physician with the prediction, diagnosis, and management of patients with diabetes. Insulin is the only beta-cell specific autoantigen thus far identified.4-6 Antibodies to insulin are found predominantly, though not exclusively, in young children developing type 1 diabetes. In insulin-naive (untreated) patients, the prevalence of antibodies to insulin is almost 100% in very young individuals and almost absent in adult onset of type 1 diabetes. Because the risk of diabetes is increased with the presence of each additional autoantibody marker, the positive predictive value of insulin antibody measurement is increased when measured in conjunction with antibodies to GAD and IA-2.2-4

1. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997 Jul; 20(7):1183-1197. PubMed 9203460

2. Bonifacio E, Bingley PJ. Islet autoantibodies and their use in predicting insulin-dependent diabetes. Acta Diabetol. 1997 Oct; 34(3):185-193 (review). PubMed 9401639

3. Verge CF, Gianani R, Kawasaki E, et al. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996 Jul; 45(7):926-933. PubMed 8666144

4. Bingley PJ, Bonifacio E, Williams AJ, Genovese S, Bottazzo GF, Gale EA. Prediction of IDDM in the general population: Strategies based on combinations of autoantibody markers. Diabetes. 1997 Nov; 46(11):1701-1710. PubMed 9356015

5. Sepe V, et al. Islet-related autoantigens and the pathogenesis of diabetes mellitus. In: Leslie RDG, ed. Molecular Pathogenesis of Diabetes Mellitus. 1997; 22:68-89.

6. Greenbaum CJ, Palmer JP, Kuglin B, Kolb H. Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assay: Results of the Fourth International Workshop on the Standardization of Insulin Autoantibody Measurement. J Clin Endocrinol Metab. 1992 May; 74(5):1040-1044. PubMed 1569152