Endocrine Abstracts

Objective

To study the predictive value of autoantibodies in progression to type 1 (T1DM) and type 2 (T2DM) diabetes after gestational diabetes (GDM) in a 23-year follow-up study.

Background

Women with GDM are at high risk for T2DM later in life, but also the risk of T1DM is increased. We have previously reported a prospective 6-year cohort study showing an association of islet cell and glutamic acid decarboxylase autoantibodies, GDM below the age of 30 years and the need for insulin treatment during pregnancy with a high risk of progression to T1DM. Recently, we reported the results of a 23-year follow-up showing that 5.7% of women with GDM developed T1DM and the disease progression was predictable with high OGTT 2-hour glucose levels during pregnancy. In addition, 50.4% of women developed T2DM after GDM with a linear incidence until the end of the study.

Study Design

This is a prospective cohort study including 391 women with GDM and 391 age-, parity–and delivery date-matched controls who delivered in 1984–1994. Four autoantibodies associated with T1DM were analysed from first trimester samples; islet cell (ICAs), glutamic acid decarboxylase (GADAs), insulin (IAAs) and insulinoma-associated antigen 2 autoantibodies (IA-2As). A follow-up questionnaire assessing later T1DM and T2DM morbidity was sent in 2012–2013. The mean follow-up time was 23.1 (18.7–28.8) years, which is to our knowledge, the longest follow-up to date.

Results

Single autoantibody positivity was detected in 12% (41/391) of the GDM cohort and in 2.3% (8/391) of the control cohort. In the GDM cohort, 2.6% (9/391) tested positive for two autoantibodies and 2.3% (8/391) for three autoantibodies, whereas only one subject in the control cohort had two autoantibodies detected. ICA positivity was found in 12.5% of the cases, followed by GADA (6.0%), IA2A (4.9%) and IAA (1.2%). In the control cohort, GADA positivity was found in 1.4%, IA2A in 0.8%, IAA in 0.6%, and ICA in 0.3% of the subjects. Detection of ICA, GADA and/or IA-2A autoantibodies decreased T1DM-free survival time and time to diagnosis. All subjects with three positive autoantibodies developed T1DM within seven years from the GDM pregnancy. Development of T2DM after GDM occurred independent of autoantibody positivity.

Conclusion

Development of T1DM can be reliably predicted with GADA and ICA autoantibodies during early pregnancy. We recommend that women with high glucose values in OGTT and insulin treatment be tested for autoantibodies to identify individuals with high risk of T1DM later in life.