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

[Familial Mediterranean fever: not to be missed]

Item does not contain fulltextFamilial Mediterranean fever (FMF) is common among Turkish and Moroccan migrants. We describe three patients with FMF. A 3-year-old girl with recurrent fever and abdominal pain who was diagnosed early with FMF and treated effectively with colchicine. An adolescent girl who required interleukin (IL)-1 blockade to achieve disease remission. And a 37-year-old woman in whom the attacks of FMF had not been recognised, but who developed end-stage kidney failure due to AA amyloidosis. Mutations in the MEFV gene underlie the disease in most but not all patients. Therefore, FMF remains a clinical diagnosis. FMF patients suffer recurrent bouts of inflammation, often with fever, serositis or arthritis. The major complication is AA amyloidosis. The inflammatory process is mediated by IL-1beta. When started early, colchicine prophylaxis can prevent amyloidosis. When colchicine fails, IL-1 blockade has shown promising results. Timely diagnosis and treatment can make the difference between near normal health and end-stage kidney failure

Cognitive impairment and MRI correlates in the elderly patients with type 2 diabetes mellitus

Item does not contain fulltextBackground: exact mechanisms underlying cognitive dysfunction in diabetes mellitus (DM) remain unclear. Imaging studies of the brain could help to identify possible structural brain lesions underlying cognitive dysfunction. Objective: to describe a detailed neuropsychological profile in patients functioning independently with type 2 DM. Secondly, correlations were studied between cognitive impairment and brain lesions on magnetic resonance imaging (MRI), i.e. periventricular hyperintensities (PVH), deep white matter lesions (DWML), medial temporal lobe atrophy (MTA), cerebral atrophy and lacunar infarcts. In addition, the influence of relevant disease variables of DM was studied. Methods: 92 patients with type 2 DM (mean age 73.2 ± 5.7 years, mean duration 13.8 ± 10.8 years) and 44 control subjects (mean age 72.9 ± 5.3 years) were included and underwent an extensive neuropsychological test battery and an MRI of the brain. Results: neuropsychological scores were worse for each cognitive domain except for memory functions after adjustment for hypertension in a group of elderly patients with type 2 DM compared to healthy control subjects. Only PVH were independently associated with motor speed, whereas all other MRI measures were not independently associated with cognitive impairment. Interactions between the different MRI measures were not present. Glycosylated haemoglobin (HbA1c) and duration of DM were significantly associated with cognitive dysfunction. Conclusions: the data of this cross-sectional study show that type 2 DM is associated with diminished cognitive function in different cognitive domains, while memory is less affected after adjustment for hypertension. The association of cognitive impairment with MRI measures is equivocal, whereas HbA1c and duration of DM were significantly associated with cognitive dysfunction.7 p

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial

Contains fulltext : 198097.pdf (publisher's version ) (Closed access)AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome

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

Contains fulltext : 208558.pdf (publisher's version ) (Open Access)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