Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus sustains glycemic control and weight loss over 48 weeks: a randomized, double-blind, parallel-group, placebo-controlled trial.

Introduction: Maintenance of drug efficacy and safety over the long term is important to investigate for progressive conditions like type 2 diabetes mellitus (T2DM). This study aimed to evaluate whether efficacy of dapagliflozin added to glimepiride observed at 24 weeks was maintained at 48 weeks, and to provide further safety and tolerability data in patients with T2DM.

Methods: This 24-week randomized, double-blind, parallel-group, placebo-controlled trial with a 24-week double-blind extension period enrolled adults whose T2DM was inadequately controlled [glycated hemoglobin (HbA1c) 7.

Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.

Aims: To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone.

Methods: This was a 52-week, randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n = 408), uptitrated over 18 weeks according to tolerability and glycaemic response to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin (≥ 1500 mg/day) with a 156-week double-blind extension period. Data over 104 weeks are reported here.

Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.

Aims: To evaluate the efficacy and safety of the selective sodium glucose co-transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise.

Methods: Patients received placebo or dapagliflozin (5 or 10 mg) once daily for 24 weeks. The primary outcome measure was change from baseline in glycated haemoglobin (HbA1c).

Small-angle x-ray scattering screening complements conventional biophysical analysis: comparative structural and biophysical analysis of monoclonal antibodies IgG1, IgG2, and IgG4.

A crucial step in the development of therapeutic monoclonal antibodies is the selection of robust pharmaceutical candidates and screening of efficacious protein formulations to increase the resistance toward physicochemical degradation and aggregation during processing and storage. Here, we introduce small-angle X-ray scattering (SAXS) to characterize antibody solution behavior, which strongly complements conventional biophysical analysis. First, we apply a variety of conventional biophysical techniques for the evaluation of structural, conformational, and colloidal stability and report a systematic comparison between designed humanized IgG1, IgG2, and IgG4 with identical variable regions.

Health-related quality of life (EQ-5D) among type 2 diabetes mellitus patients treated with dapagliflozin over 2 years.

Aims: This study evaluated health status and health-related quality of life (HRQOL) among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing glucose excretion, in a double-blind, randomised clinical trial.

Methods: Subjects with T2DM who had inadequate glycaemic control on metformin alone were enrolled in a 24-week, double-blind, randomised, placebo-controlled study with a 78-week extension period to evaluate the effect of dapagliflozin in combination with metformin. Subjects treated with dapagliflozin 10 mg + metformin (n = 89) were compared with subjects treated with placebo + metformin (n = 91) at baseline and at weeks 24, 50 and 102.

Assessment of in situ adipose tissue inflammation by microdialysis.

Background: Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore investigated the utility of microdialysis to study in situ AT interstitial inflammatory protein levels.

Changes in weight loss-related quality of life among type 2 diabetes mellitus patients treated with dapagliflozin.

Aims: This study evaluated change in health-related quality of life (HRQOL) associated with ongoing weight change among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing urinary glucose excretion and is associated with body weight reductions.

Methods: Patients with T2DM who had inadequate glycaemic control on metformin (MET) alone were enrolled in a 24-week, double-blind, randomized, placebo-controlled study with a 78-week extension to evaluate the effect of dapagliflozin + MET on body weight. Patients also completed the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes Weight Questionnaire-9 (SHIELD-WQ-9), a weight change-related HRQOL survey.

Vitamin B12 as a potential compliance marker for fish intake.

Objectives: The aim of the present study was to investigate whether the following four markers: vitamin B12, selenium, vitamin D, and parvalbumin may be used as compliance markers for fish intake.

Methods: Blood samples from a randomized cross-over herring intervention study (n = 32) were analysed by HPLC and immunochemistry. The criteria were that plasma or serum concentrations of candidate compliance markers after the herring diet should increase significantly compared to starting concentrations.

Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin.

Aims: Dapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long-term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.

Methods: This randomized, double-blind, placebo-controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.

Wildtype and A30P mutant alpha-synuclein form different fibril structures.

Parkinson's Disease (PD) is a neurodegenerative movement disorder affecting millions of people worldwide. One of the key players in the development of the disease is the protein α-synuclein (aSN), which aggregates in the brain of PD patients. The aSN mutant A30P has been reported to cause early-onset familial PD and shows different aggregation behavior compared to wt aSN.

Low-dose growth hormone for 40 weeks induces HIV-1-specific T cell responses in patients on effective combination anti-retroviral therapy.

Recombinant human growth hormone (rhGH) administered to combination anti-retroviral therapy (cART)-treated human immunodeficiency virus-1 (HIV-1)-infected individuals has been found to reverse thymic involution, increase total and naive CD4 T cell counts and reduce the expression of activation and apoptosis markers. To date, such studies have used high, pharmacological doses of rhGH. In this substudy, samples from treated HIV-1(+) subjects, randomized to receive either a physiological dose (0·7 mg) of rhGH (n = 21) or placebo (n = 15) daily for 40 weeks, were assessed.

MicroRNA normalization candidates for quantitative reverse-transcriptase polymerase chain reaction in real time in lesional and nonlesional psoriatic skin.

Background: MicroRNA (miRNA) technology is an evolving research area and quantitative reverse-transcriptase polymerase chain reaction in real time (qPCR) is an important investigational tool. The small noncoding RNA candidates used for normalization in psoriatic skin biopsies have never been sufficiently validated.

Objectives: To identify a reliable normalization method for miRNA analysis with qPCR in psoriatic skin.

[Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride].

Aims: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM.

Inflammation in HIV-infected patients: impact of HIV, lifestyle, body composition, and demography - a cross sectional cohort study.

Objectives: To examine mechanisms underlying the increased inflammatory state of HIV-infected patients, by investigating the association of HIV-related factors, demography, lifestyle, and body composition with the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR).

Methods: suPAR was measured in EDTA-plasma and associated with HIV-related factors (HIV-duration, combination antiretroviral treatment (cART), nadir CD4+ cell count, CD4+ cell count, and HIV RNA); demography; lifestyle; and body composition determined by Dual energy X-ray Absorptiometry (DXA) scan, in multiple linear regression analyses adjusted for biological relevant covariates, in a cross-sectional study of 1142 HIV-infected patients.

Results: Increased suPAR levels were significantly associated with age, female sex, daily smoking, metabolic syndrome and waist circumference.

Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial.

Aim: Dapagliflozin is a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor under development as a treatment for type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of dapagliflozin monotherapy in Japanese T2DM patients with inadequate glycaemic control.

Methods: Patients (n = 279) were randomized to receive dapagliflozin (1, 2.

Progression and CSF Inflammation after Eradication of Oligoclonal Bands in an MS Patient Treated with Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma.

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.

Aims: To describe the effects of allo-HCT on the course of MS in a 49-year-old woman with longstanding progressive MS who was treated with allo-HCT for follicular lymphoma.

Methods: Non-myeloablative conditioning allo-HCT, examination for IgG oligoclonal bands and measurement of CXCL13 and matrix metalloproteinase-9 (MMP-9) concentration in the cerebrospinal fluid (CSF).

Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.

Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity.

Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.

Aims: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment.

Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria.

Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta.

[Computer tomography angiography of the cerebral and cervical vessels].

Due to the high temporal and spatial resolution in multislice computed tomography it is possible to perform high-quality computer tomography angiography (CTA) of the cerebral and cervical vessels. Compared to digital subtraction angiography (DSA), a method that is still considered to be the golden standard, CTA is faster and can be performed using a minimal invasive technique. In this paper we outline the clinical indications for performing CTA (aneurysms, stroke, vasospasms, arterio-venous malformations, dissection).

Structural characterization of prefibrillar intermediates and amyloid fibrils by small-angle X-ray scattering.

Structural investigation of the species present during protein fibrillation is of tremendous importance, yet complicated by the equilibrium between species of very different sizes and life-times. Small-angle X-ray scattering may be applied to solve this problem, providing both information about the process (number of species present and volume fractions of individual species) and low-resolution three-dimensional shape reconstructions of individual species. Here, we describe in detail the challenges associated with the approach, exemplified using data from fibrillating insulin or α-synuclein samples.

Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.

Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.

Design And Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial.

Aims: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM.

Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a stable plasma biomarker associated with inflammation and disease. This study tested the association between suPAR levels and incident respiratory, gastrointestinal, or other types of cancer in initially cancer-free individuals from a general population-based prospective study.

Methods: Baseline plasma samples, baseline characteristics, and follow-up data were available from 2,656 individuals from the population-based Danish MONICA10 (MONItoring trends and determinants of CArdiovascular disease) study, followed for a median of 12.

Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population.

Background: Low-grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type-2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease.

Objective: The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population.