Autoimmunity and familial risk of type 1 diabetes.

There is evidence that the process leading to type I diabetes may start in early infancy or already in utero. Even though diabetes-associated antibodies can be detected in up to half of the pregnancies of mothers with type I diabetes, pregnancy itself has no major effect on these antibodies. If such antibodies are present in the mother, they are transferred to the fetal circulation and are detectable in cord blood. Most of the transplacentally transferred antibodies disappear by 6 months of age, but may persist even longer. Antibodies present in cord blood may represent true induction of beta-cell autoimmunity, but such a phenomenon is extremely rare. The offspring of affected mothers have a 2% to 3% risk of type I diabetes, which is about one third of that in the offspring of affected fathers. A novel conceivable explanation is that exogenous insulin transplacentally transferred in immune complexes might lead to the induction of tolerance to insulin, which may be the primary autoantigen in type I diabetes. The possible protective or predisposing effect of diabetes-associated antibodies detectable at birth on progression to clinical type I diabetes later will be assessed in ongoing prospective birth cohort studies.