PREDICTION OF TYPE-1 DIABETES POSTPARTUM IN PATIENTS WITH GESTATIONALDIABETES-MELLITUS BY COMBINED ISLET-CELL AUTOANTIBODY SCREENING - A PROSPECTIVE MULTICENTER STUDY

Women with gestational diabetes mellitus (GDM) have a considerable ris k of developing diabetes later in Life. To determine the predictive va lue of autoantibody markers in gestational diabetic pregnancy for the development of type I diabetes postpartum, we tested 437 patients with GDM (289 women treated with diet only [GDM-A] and 148 requiring insul in treatment during pregnancy [GDM-B]) for antibodies to islet cells ( ICAs), GAD (GADAs), and tyrosine phosphatase ICA512/IA-2 (IA2As). We p rospectively followed them with repeated oral glucose tolerance tests and antibody determinations for up to 7 years postpartum (mean, 1.6 ye ars; range, 0-7.2 years). The cumulative risk of diabetes up to 5 year s postpartum was 17% (95% CI 12-22%). The risk of type 1 diabetes was 3% (2-5%) by 9 months and 7% (4-9%) 2 years after delivery. At deliver y, 8.5% of all patients were ICA(+), 9.5% were GADA(+), 6.2% were IA2A (+), and 18.1% were positive for at least one antibody (12.6% for GDM- A vs. 30.4% for GDM-B, P < 0.0001), During follow-up, GADAs persisted in 75%, ICAs in 35%, and IA2As in 30% of the subjects positive for the respective marker at delivery By 2 years postpartum, 29% (19-39%) of patients positive for at least one antibody developed type 1 diabetes, compared with 2% (1-4%) of antibody-negative patients (P < 0.0001). T hereby, the risk for type I diabetes 2 years postpartum increased with the number of antibodies present at delivery from 17% (6-28%) for one antibody, to 61% (30-91%) for two antibodies, and to 84% (55-100%) fo r 3 antibodies. Risk of progression to type 1 diabetes postpartum was also associated with the status of parity. Women with one or more preg nancies before the index pregnancy had a higher risk for type 1 diabet es 2 years after delivery (14.7% [4.9,-24.5%]) than women having their first (i.e., index) pregnancy(5% [2.9-7.1%]) (P < 0.006). A compariso n of different prediction strategies showed that single antibody scree ning with GADA yielded the highest sensitivity of 63% (45-75%), compar ed with ICA (48% [31-65%]) and IA2A (34% [13-47%]). Combined screening with two autoantibodies increased sensitivity to 74% (58-90%) and 75% (60-92%) when using GADA plus ICA or GADA plus IA2A, respectively. Sc reening with all three markers improved sensitivity further to 82% (67 -100%). beta-cell autoantibodies determined at delivery in women with GDM are highly predictive for the development of type 1 diabetes postp artum. Autoantibody screening in pregnant women with GDM from populati ons at high risk for type 1 diabetes should therefore be considered to allow early diagnosis and appropriate therapy.