Background: The prevalence of thyroid dysfunction in pregnancy and in the first postpartum year (postpartum thyroid dysfunction (PPTD)) in women with diabetes mellitus type 1 (DM1) is known to be higher than in the general population. To assess prevalence, incidence and risk factors in The Netherlands we performed a prospective cohort study. Design: From 1994 to 1998, 126 women with DM1 from eight Dutch clinics were included. TSH, free thyroxine, free tri-iodothyronine and anti-thyroid peroxidase antibodies (TPO-ab) were measured prepregnancy, in the first and last trimester of pregnancy and at 1.5, 3, 6, 9 and 12 months after delivery. Results: Eighty-two women completed the study. Thyroid dysfunction during pregnancy was observed in 22.5% (first trimester) and 18.4% (third trimester), and mostly consisted of subclinical hypothyroidism. Baseline characteristics of women with thyroid dysfunction in pregnancy did not differ from those without thyroid dysfunction. Overt PPTD was seen in 15.9%. Incidence of PPTD was 10%. Patients with PPTD were slightly older than those without PPTD and the prevalence of TPO-ab was higher in these women. Conclusion: In women with DM1 the prevalence of thyroid dysfunction during pregnancy and overt PPTD is 3-fold higher than in the general Dutch population. Risk factors are age and TPO-ab. Given the possible impact on psychomotor development of the offspring and on well-being of the mother these data suggest there is a case for screening (pre-)pregnant women with DM1 for TSH and TPO-ab.

IntroductionIn women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.MethodsThe SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration numberNTR6134; Pre-results.