Diabetes-related autoantibodies and gestational diabetes.

HETEROGENEITY OF AUTOIMMUNE DIABETES: AN OVERVIEW — Autoimmune diabetes is caused by the destruction of -cells of pancreatic islets by an immune-mediated process, promoted by the interaction of genetic and environmental factors (4). Autoantibodies (AAs) against pancreatic -cell antigens precede the clinical onset of type 1 diabetes (4). Circulating islet cell antibodies, originally described by indirect immunofluorescence in 1974 (5), have been demonstrated in the great majority of individuals with type 1 diabetes, both at the preclinical state and at the onset of clinically overt diabetes, and they persist in the circulation for a long time. Islet cell AAs include autoantibodies to islet cell cytoplasm (islet cell autoantibodies [ICAs]), to native insulin (insulin autoantibodies [IAAs]), to GAD (GADA) (6–8), and to tyrosine phosphatases (insulinoma-associated antigens IA-2A and IA-2 ) (9,10). Age not only modifies the risk of autoimmune diabetes, but also the presence of AAs, the intensity of -cell destruction, the rate of progression to overt diabetes, and the degree of residual insulin secretion. Approximately 30% of subjects with classic autoimmune diabetes (type 1A diabetes) present after age 35 years (11). Childhood autoimmune diabetes is associated with an increased prevalence of alleles DR3, DQB1*0201 and DR4, and DQB1*0302, with the proportion of heterozygotes declining with age at diagnosis (12). Children with the allele HLA DR2, DQB1*0602, almost never develop diabetes, whereas this allele confers a much lower protection for adult-onset autoimmune diabetes (13). Since the discovery of AAs against islet cell antigens, it has been recognized that a fraction of adults considered to have type 2 diabetes probably have autoimmune diabetes and that the presence of GADAs indicates a strong possibility of requiring insulin treatment earlier. These patients with adult-onset autoimmune diabetes can be initially easily misclassified as having type 2 diabetes. Actually, assessment of diabetes-related autoantibodies (DRAs) might allow them to be classified as having latent autoimmune diabetes in adults (LADA). Characteristically, they display a lower rate of metabolic syndrome than patients with type 2 diabetes (14). The distinction between adult-onset type 1 diabetes and LADA is sometimes difficult, but, characteristically, patients with LADA evolve slowly toward insulin requirement (within 6 years) and older patients with LADA show even a slower progression (15,16). DRAS AND DIABETIC PREGNANCY