Diabetes-Related Autoantibodies and Gestational Diabetes
- Alberto de Leiva, MD, PHD, MHE, FACE123,
- Dídac Mauricio, MD, PHD1 and
- Rosa Corcoy, MD, PHD123
- 1Servei d'Endocrinologia i Nutrició, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- 2Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
- 3Centro de Investigación Biomédica del Área de Bioingeniería, Biomateriales y Nanotecnología, Instituto de Salud Carlos III, Barcelona, Spain
- Address correspondence and reprint requests to Prof. Dr. Alberto de Leiva, Servei d'Endocrinologia i Nutrició, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Avinguda Sant Antoni M. Claret, 167, 08025, Barcelona, Spain. E-mail: aleiva{at}santpau.es
- AA, autoantibody
- DRA, diabetes-related autoantibody
- GADA, autoantibodies to GAD
- IA, insulin antibody
- IAA, insulin autoantibody
- ICA, islet cell autoantibody
- LADA, latent autoimmune diabetes in adults
Gestational diabetes mellitus (GDM) has long been recognized as a heterogeneous disorder (1,2), with autoimmunity against the β-cell contributing in a small subset of patients (3).
HETEROGENEITY OF AUTOIMMUNE DIABETES: AN OVERVIEW—
Autoimmune diabetes is caused by the destruction of β-cells of pancreatic islets by an immune-mediated process, promoted by the interaction of genetic and environmental factors (4). Autoantibodies (AAs) against pancreatic β-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-2β) (9,10).
Age not only modifies the risk of autoimmune diabetes, but also the presence of AAs, the intensity of β-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 …
