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

Middellandse Zeekoorts: mis het niet

Familial 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-1β. 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 failur

Ethnic Minorities with Diabetes Differ in Depressive and Anxiety Symptoms and Diabetes-Distress

Objective. To determine the association between ethnicity, diabetes-distress, and depressive and anxiety symptoms in adult outpatients with diabetes. Research Design and Methods. Diabetes-distress (Problem Areas in Diabetes Scale, PAID5), depressive and anxiety symptoms (Extended Kessler-10, EK10), and quality of life (Short-Form 12, SF12) were assessed in an ethnic diverse diabetes outpatient population of a teaching hospital in Amsterdam. Descent of one's parents and self-classified ethnicity were obtained to define ethnicity. HbA1c, clinical data, and socioeconomic status were derived from the medical charts. Based on established cut-offs for PAID5- and EK10-scores, emotional distress was dichotomized for the purpose of logistic regression analyses. Results. Of 1007 consecutive patients approached, 575 participated. Forty-nine percent were of non-Dutch ethnicity and 24.7% had type 1 diabetes. Diabetes-distress was reported by 12.5% of the native Dutch patients and by 22.0%, 34.5%, and 42.6% of the Surinamese, Turkish, and Moroccan patients, respectively. Prevalence of depressive symptoms was 9.4% in native Dutch patients and 20.4%, 34.5%, and 27.3% in the other groups mentioned. Diabetes-distress and Moroccan origin were significantly associated (OR = 3.60, p<.01) as well as depressive symptoms and Turkish origin (OR = 4.23, p=.04). Conclusions. Different ethnic minorities with diabetes vary in their vulnerability for emotional distress, warranting clinical attention. Future research should elucidate explanatory factors and opportunities for tailored interventions

Diabetes distress is associated with adverse pregnancy outcomes in women with gestational diabetes: A prospective cohort study

Background: Around 12% of pregnant women develop gestational diabetes mellitus (GDM), which is associated with increased health risks for both mother and child and pre- and postpartum depression. Little is known about the relationship of GDM with diabetes-specific emotional distress (diabetes distress). The aims of this study are to assess the prevalence of diabetes distress in GDM and its association with adverse pregnancy outcomes. Methods: A prospective cohort study was carried out in an Amsterdam based teaching hospital with an ethnic diverse population. Women diagnosed with GDM completed a set of questionnaires at three time points. Questionnaires consisted of Problem Areas in Diabetes Scale 5 (PAID-5) for diabetes distress (T0-T1), Patient Health Questionnaire 9 (PHQ-9) for depressive symptoms (T0-T2), and questions to assess adverse pregnancy outcomes (T2). Adverse pregnancy outcomes (collected via self-report and if feasible from the medical records) were defined as hypertension, pre-eclampsia, caesarean section, severe perineal tearing, postpartum hemorrhage, postpartum depression, shoulder dystocia, neonatal hospitalization, macrosomia, jaundice, hypoglycemia and other (among which low heart rate, fever, hypoxia). Adverse pregnancy outcomes were dichotomized into none and 1 or more. Additional information was collected from the medical charts. Missing data were imputed via predictive mean matching and a multivariable logistic regression analysis was performed with diabetes distress, depressive symptoms, socioeconomic status, parity and ethnicity as predictors and age, HbA1c, and BMI as covariates. Results: A total of 100 women were included, mean age 32.5 (4.1), mean BMI 26.7 (4.8), 71% were of non-Dutch ethnic background. Elevated diabetes distress (PAID score ≥ 8) was reported by 36% of the women. Multivariable logistic regression analyses revealed that both high diabetes distress (OR 4.70, p =.02) and parity (OR 0.21, p =.02) but not antepartum depressive symptoms were related to adverse pregnancy outcomes. Conclusions: Diabetes distress is likely in women with GDM and our findings suggest an association between both diabetes distress, parity and adverse pregnancy outcomes in women with GDM. This warrants replication and further research into the underlying mechanisms explaining the impact of diabetes distress in GDM and potential interventions to reduce distress

Brain lesions on MRI in the elderly patients with type 2 Diabetes Mellitus.

Background and Purpose: Diabetes mellitus (DM) type 2 has been associated with poor cognitive performance and dementia, particularly in elderly patients. The exact mechanisms underlying the cognitive dysfunction in DM remain unclear. Imaging studies of the brain could be helpful to give more insight into possible structural brain lesions underlying these cognitive dysfunctions. Therefore, we performed a study in independently living patients with DM type 2 in order to investigate the association between DM and brain imaging abnormalities. Methods: The study population consisted of 45 patients with DM type 2 without hypertension (mean age 73.4 ± 5.1 years, mean duration 16.5 ± 11.5 years), 45 patients with DM type 2 and hypertension (mean age 73.5 ± 6.1 years, mean duration 11.9 ± 9.2 years) and 44 control subjects (mean age 73.1 ± 5.4 years). All patients and control subjects underwent an MRI of the brain. White matter lesions (WML), cerebral atrophy and medial temporal lobe atrophy were rated by a standardized visual rating scale. Lacunar infarcts were defined as focal hypo-intensities on fluid-attenuated inversion recovery sequences with a hyperintense rim around it. Results: WML occurred more frequently in diabetic patients with hypertension as well as without hypertension. Significantly more deep WML were found in DM patients with and without hypertension when compared to control subjects, whereas no difference was found in the occurrence of periventricular hyperintensities. In all 3 groups, lacunar infarcts occurred sporadically. A trend towards higher atrophy scores was seen in patients with DM compared to control subjects. Conclusions: The data of this cross-sectional study suggest that type 2 DM is an independent risk factor for deep WML in the independently living elderly patients. Copyright © 2007 S. Karger AG

Simplification of the diagnostic management of suspected deep vein thrombosis

Background: The standard diagnostic approach in patients with suspected deep vein thrombosis is to repeat the compression ultrasonography after 1 week in all patients with an initial normal result. We hypothesized that a normal finding of a D-dinner assay safely obviates the need for repeated ultrasonography. In addition, we evaluated the potential value of a pretest probability assessment for this purpose. Methods: At presentation, consecutive outpatients with suspected thrombosis underwent independent assessment by means of ultrasonography of the proximal veins, a wholeblood D-dieter assay, and a pretest clinical model. Patients with normal ultrasonographic findings and an abnormal D-dieter assay result were scheduled for repeated ultrasonography. We evaluated the incidence of symptomatic venous thromboembolic complications during a 3-month follow-up, and the value of clinical pretest probability with ultrasonography or D-dieter assay in scenario analyses. Results: We studied 1756 patients with prevalence of thrombosis of 22%. At entry, results of the D-dieter assay and ultrasonography were normal in 828 patients (47%). Of these, 6 returned with confirmed symptomatic venous thromboembolism (complication rate, 0.7%; 95% confidence interval [CI], 0.3%-1.6%). Repeated ultrasonography was avoided in 61% of the patients with an initial normal test result. Scenario analyses disclosed that the complication rate was 1.6% (95% CI, 0.8%-2.6%) in those with a low clinical pretest probability and a normal result of ultrasonography at referral, whereas this figure was 1.8% (95% CI, 0.9%-3.3%) in patients with a low clinical probability result and a normal result of the D-dieter assay at referral. Conclusions: It is safe to withhold repeated ultrasonography in patients with suspected deep vein thrombosis who have normal results of ultrasonograpy and the SimpliRED D-dieter assay at presentation. The combination of a low clinical pretest probability with a normal result of compression ultrasonography or the D-dimer assay appears to be equally safe in refuting the diagnosis of deep vein thrombosi

Dapagliflozin for prednisone-induced hyperglycemia in acute exacerbation of chronic obstructive pulmonary disease

This study aimed to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in subjects with prednisone-induced hyperglycemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicenter double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared to placebo. Glycemic control and incidence of hypoglycemia were measured through a blinded subcutaneous continuous glucose measurement device. Subjects in the dapagliflozin group, spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and this was 53.6 ± 23.4% in the placebo group (p = 0.96). Mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (p = 0.66). One patient using dapagliflozin and 2 patients using placebo experienced a symptomatic hypoglycemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycemia compared to placebo. Dapagliflozin did not result in better glycemic control compared to placebo in patients with prednisone-induced hyperglycemia during AECOP

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