Type 1 and type 2 diabetes after gestational diabetes: a 23 year cohort study.

AIMS/HYPOTHESIS: The aim of this work was to examine the progression to type 1 and type 2 diabetes after gestational diabetes mellitus (GDM) in a 23 year follow-up study. METHODS: We carried out a cohort study of 391 women with GDM diagnosed by an OGTT or the use of insulin treatment during pregnancy, and 391 age- and parity-matched control participants, who delivered in 1984-1994 at the Oulu University Hospital, Finland. Diagnostic cut-off levels for glucose were as follows: fasting, ≥4.8 mmol/l; 1 h, ≥10.0 mmol/l; and 2 h, ≥8.7 mmol/l. Two follow-up questionnaires were sent (in 1995-1996 and 2012-2013) to assess the progression to type 1 and type 2 diabetes. Mean follow-up time was 23.1 (range 18.7-28.8) years. RESULTS: Type 1 diabetes developed (5.7%) during the first 7 years after GDM pregnancy and was predictable at a 2 h OGTT value of 11.9 mmol/l during pregnancy (receiver operating characteristic analysis: AUC 0.91, sensitivity 76.5%, specificity 96.0%). Type 2 diabetes increased linearly to 50.4% by the end of the follow-up period and was moderately predictable with fasting glucose (AUC 0.69, sensitivity 63.5%, specificity 68.2%) at a level of 5.1 mmol/l (identical to the fasting glucose cut-off recommended by the International Association of Diabetes and Pregnancy Study Groups [IADPSG) and WHO]). CONCLUSIONS/INTERPRETATION: All women with GDM should be intensively monitored for a decade, after which the risk for type 1 diabetes is minimal. However, the incidence of type 2 diabetes remains linear, and therefore individualised lifelong follow-up is recommended.

Autoantibodies predict type 1 diabetes after gestational diabetes - a 23-year cohort study.

Objective: To study the predictive value of autoantibodies for type 1 (T1DM) and type 2 (T2DM) diabetes morbidity after gestational diabetes (GDM) in a 23-year follow-up study. Design: Prospective population-based cohort study. Methods: We studied 391 women with GDM, and 391 age- and parity-matched controls, who delivered in 1984-1994. Four autoantibodies were analysed in first-trimester blood samples: islet cell autoantibodies (ICAs), glutamic acid decarboxylase autoantibodies (GADAs), insulin autoantibodies (IAAs) and insulinoma-associated antigen-2 autoantibodies (IA-2As). Two follow-up questionnaires (1995-1996, 2012-2013) were sent to assess development of T1DM and T2DM. Predictive value of autoantibodies and clinical factors were analysed by conditional linear regression and ROC analyses. Results: Single autoantibody positivity was detected in 12% (41/342) of the GDM cohort and in 2.3% (8/353) of the control cohort. In the GDM cohort, 2.6% (9/342) tested positive for two autoantibodies and 2.3% (8/342) for three autoantibodies, whereas only one subject in the control cohort had two autoantibodies. ICA positivity was found in 12.5% of the cases, followed by GADA (6.0%), IA-2A (4.9%) and IAA (1.2%). In the control cohort, GADA positivity was found in 1.4%, IA-2A 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.