SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In 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. METHODS: The 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 DISSEMINATION: The 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 NUMBER: NTR6134; Pre-results.

Cardiac diastolic dysfunction and metabolic syndrome in young women after placental syndrome.

OBJECTIVE: To estimate whether women with a recent history of a placental syndrome and concomitant metabolic syndrome have reduced cardiac diastolic function. METHODS: In this cohort study, women with a history of a placental syndrome were included. We assessed body mass index, blood pressure, fasting serum lipids, glucose and insulin levels, and 24-hour urinary protein and albumin output after an interval of at least 6 months postpartum. Cardiac diastolic function was assessed by echocardiography. RESULTS: Metabolic syndrome was found in 22% of the women evaluated. Diastolic dysfunction was seen in 24% of the women with the metabolic syndrome compared with 6.3% in those without (odds ratio 4.77, 95% confidence interval 2.18-10.41; adjusted odds ratio 6.09, 95% confidence interval 2.64-14.04). Univariable analysis showed that all the constituents of the metabolic syndrome related to diastolic dysfunction. CONCLUSION: In women with a history of placental syndrome complicating pregnancy, the presence of metabolic syndrome increases the risk of cardiac diastolic dysfunction fourfold. LEVEL OF EVIDENCE: II.

Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome.

OBJECTIVE: To determine the prevalence of the metabolic syndrome postpartum in women with a history of pregnancy complicated by early-onset vascular disorders compared with women with late-onset disorders. METHODS: In this retrospective cohort study 849 women with a history of pregnancy complicated by vascular disorders (preeclampsia; gestational hypertension; hemolysis, elevated liver enzymes, low platelets syndrome; eclampsia; placental abruption; fetal growth restriction; and stillbirth as a result of placental insufficiency) were divided into early-onset (delivery before 32 weeks of gestation, n=376) and late-onset (delivery at or beyond 32 weeks, n=473). By use of four internationally accepted criteria to diagnose metabolic syndrome, we compared its prevalence in both groups using odds ratios (ORs), adjusted for maternal age, smoking, alcohol and coffee consumption, birth weight centile, stillbirth, and interval between delivery and measurements. RESULTS: The metabolic syndrome was present in 15-25% of women after early-onset vascular-complicated pregnancy and in 10-14% of women after late-onset disease, depending on the criteria set used; adjusted OR 2.51 (95% confidence interval [CI] 1.66-3.80) using World Health Organization criteria; adjusted OR 2.01 (95% CI 1.37-2.96) using International Diabetes Federation criteria; adjusted OR 2.16 (95% CI 1.31-3.55) using Third Adult Treatment Panel (ATPIII) criteria; and adjusted OR 2.02 (95% CI 1.28-3.17) using Third Adult Treatment Panel updated criteria. CONCLUSION: The prevalence of the metabolic syndrome postpartum is twice as high in women with a history of early-onset (delivery before 32 weeks) compared to late-onset vascular-complicated pregnancy (delivery at or beyond 32 weeks). LEVEL OF EVIDENCE: II.