Insulin autoantibodies in cord blood from neonates with and without a sibling with type 1 diabetes-prevalence and characterization

Objective: Insulin autoantibodies (INSAAbs) are associated with the onset and progression of type 1 diabetes. Their presence in siblings of patients with type 1 diabetes precedes the development of overt diabetes. The precise time of INSAAbs onset and their relationship to diabetes triggering factors remains unknown. We sought to determine the prevalence and nature of INSAAbs in neonates with and without a sibling affected by type 1 diabetes. Methods: One hundred and twenty four healthy non-diabetic neonates were studied; 12 had a sibling with type 1 diabetes and 112 had no first-degree relatives with the disease. Cord blood samples were collected from the neonates and their mothers at birth and again from the neonates whose initial sample was INSAAbs-positive at 3 months of age. INSAAbs titer was tested using a competitive radiobinding assay. To further characterize the nature of this binding capacity, the assay was repeated twice, before and after incubation with protein A or insulin-like growth factor (IGF-1). Results: Specific insulin-binding activity was noted at birth in 8/12 neonates with a diabetic sibling (66%) and in 79/112 (70%) control newborns. None of the maternal samples from either group were INSAAb-positive. By age 3 months, INSAAb levels had normalized in 90% of the neonates in both groups. Protein A did not induce precipitation of bound insulin complexes, and IGF-1 failed to displace bound insulin from the cord blood. Conclusions: Although more than 70% of cord blood samples specifically bound insulin, this action is probably unrelated to the passive transfer of IgG antibodies during pregnancy or to cross-reactivity with the IGF-binding proteins. Furthermore, INSAAb cannot be a predictive sign for early development of type 1 diabetes in the first 3 months of age.