Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

The Belle II SVD detector

The Silicon Vertex Detector (SVD) is one of the main detectors in the Belle II experiment at KEK, Japan. In combination with a pixel detector, the SVD determines precise decay vertex and low-momentum track reconstruction. The SVD ladders are being developed at several institutes. For the development of the tracking algorithm as well as the performance estimation of the ladders, beam tests for the ladders were performed. We report an overview of the SVD development, its performance measured in the beam test, and the prospect of its assembly and commissioning until installation

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

Association between Insomnia Symptoms and Hemoglobin A1c Level in Japanese Men

Background: The evidence for an association between insomnia symptoms and blood hemoglobin A1c (HbA1c) level has been limited and inconclusive. The aim of this study was to assess whether each symptom of initial, middle, and terminal insomnia influences HbA 1c level in Japanese men. Methods: This cross-sectional study examined 1,022 male workers aged 22–69 years with no history of diabetes at a Japanese company’s annual health check-up in April 2010. High HbA1c was defined as a blood level of HbA1c $6.0%. Three types of insomnia symptoms (i.e., difficulty in initiating sleep, difficulty in maintaining sleep, and early morning awakening) from the previous month were assessed by 3 responses (i.e., lasting more than 2 weeks, sometimes, and seldom or never [reference group]). Results: The overall prevalence of high HbA1c was 5.2%. High HbA1c was positively and linearly associated with both difficulty in maintaining sleep (P for trend =.002) and early morning awakening (P for trend =.007). More specifically, after adjusting for potential confounding factors, high HbA1c was significantly associated with difficulty in maintaining sleep lasting more than 2 weeks (adjusted odds ratio, 6.79 [95 % confidence interval, 1.86–24.85]) or sometimes (2.33 [1.19–4.55]). High HbA1c was also significantly associated with early morning awakening lasting more than 2 weeks (3.96 [1.24–12.59]). Conclusion: Insomnia symptoms, particularly difficulty in maintaining sleep and early morning awakening, were found t