PREDICTION OF TYPE-1 DIABETES POSTPARTUM IN PATIENTS WITH GESTATIONALDIABETES-MELLITUS BY COMBINED ISLET-CELL AUTOANTIBODY SCREENING - A PROSPECTIVE MULTICENTER STUDY
M. Fuchtenbusch et al., PREDICTION OF TYPE-1 DIABETES POSTPARTUM IN PATIENTS WITH GESTATIONALDIABETES-MELLITUS BY COMBINED ISLET-CELL AUTOANTIBODY SCREENING - A PROSPECTIVE MULTICENTER STUDY, Diabetes, 46(9), 1997, pp. 1459-1467
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.