Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Association Study between T2DM and CAPN10 SNP-19 (rs3842570) Polymorphism in Navi Mumbai Population

Genetic research has brought a lot of new knowledge in the area of genetic predisposition of type 2 diabetes mellitus (T2DM). It has been proposed that excessive insulin resistance and obesity are also responsible for the higher incidence of type 2 diabetes. Calpain-10 (CAPN10) is a member of a large family of intracellular proteases. The polymorphism at deletion/insertion SNP19 of this gene influences susceptibility to T2DM. The aim of the study was to determine whether calpain-10 (ins/del SNP19) polymorphism contributes significantly to susceptibility to T2DM in population of Navi Mumbai. The study included randomly selected 75 patients of which 33 had T2DM and 42 served as control subjects. Mean waist-to-hip ratio, HDL, LDL, VLDL, cholesterol, and triglyceride showed no difference whereas mean of age, FBS, and body mass index showed significant differences between the control and diabetes subjects. Genotyping of calpain-10 (ins/del SNP19) polymorphism was performed by polymerase chain reaction method. Among 75 participants, for allele-specific SNP19, genotype frequencies of allele1 (2R-32 bp), heterozygous allele (2R-3R 32 bp), and allele 2 (3R-32 bp) were 20 (26.6%), 36 (48%), and 19 (25.3%) observed, respectively. The results from the present study have indicated that CAPN10 (SNP19) shows no significant association with T2DM and more extensive studies on T2DM using candidate gene approach may provide better preventive measures and potential disease diagnostic tools

SPART: A versatile and standardized data exchange format for species partition information

International audienceA wide range of data types can be used to delimit species and various computer-based tools dedicated to this task are now available. Although these formalized approaches have significantly contributed to increase the objectivity of species delimitation (SD) under different assumptions, they are not routinely used by alpha-taxonomists. One obvious shortcoming is the lack of interoperability among the various independently developed SD programs. Given the frequent incongruences between species partitions inferred by different SD approaches, researchers applying these methods often seek to compare these alternative species partitions to evaluate the robustness of the species boundaries. This procedure is excessively time consuming at present, and the lack of a standard format for species partitions is a major obstacle. Here, we propose a standardized format, SPART, to enable compatibility between different SD tools exporting or importing partitions. This format reports the partitions and describes, for each of them, the assignment of individuals to the “inferred species”. The syntax also allows support values to be optionally reported, as well as original trees and the full command lines used in the respective SD analyses. Two variants of this format are proposed, overall using the same terminology but presenting the data either optimized for human readability (matricial SPART) or in a format in which each partition forms a separate block (SPART.XML). ABGD, DELINEATE, GMYC, PTP and TR2 have already been adapted to output SPART files and a new version of LIMES has been developed to import, export, merge and split them

SPART: A versatile and standardized data exchange format for species partition information

A wide range of data types can be used to delimit species and various computer‐based tools dedicated to this task are now available. Although these formalized approaches have significantly contributed to increase the objectivity of species delimitation (SD) under different assumptions, they are not routinely used by alpha‐taxonomists. One obvious shortcoming is the lack of interoperability among the various independently developed SD programs. Given the frequent incongruences between species partitions inferred by different SD approaches, researchers applying these methods often seek to compare these alternative species partitions to evaluate the robustness of the species boundaries. This procedure is excessively time consuming at present, and the lack of a standard format for species partitions is a major obstacle. Here, we propose a standardized format, SPART, to enable compatibility between different SD tools exporting or importing partitions. This format reports the partitions and describes, for each of them, the assignment of individuals to the “inferred species”. The syntax also allows support values to be optionally reported, as well as original trees and the full command lines used in the respective SD analyses. Two variants of this format are proposed, overall using the same terminology but presenting the data either optimized for human readability (matricial SPART) or in a format in which each partition forms a separate block (SPART.XML). ABGD, DELINEATE, GMYC, PTP and TR2 have already been adapted to output SPART files and a new version of LIMES has been developed to import, export, merge and split them.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171262/1/men13470-sup-0001-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171262/2/men13470.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171262/3/men13470_am.pd