Tomography of (2, 1) and (3, 2) magnetic island structures on Tokamak Fusion Test Reactor

High-resolution electron cyclotron emission (ECE) image reconstruction has been used to observe (m,n)=(2,1) and (3, 2) island structures on Tokamak Fusion Test Reactor [Plasma Phys. Controlled. Fusion 33, 1509 (1991)], where m and n are the poloidal and the toroidal mode number, respectively. The observed island structure is compared with other diagnostics, such as soft x-ray tomography and magnetic measurements. A cold elliptic island is observed after lithium pellet injection. Evidence for the enhancement of the heat transfer due to the island is observed. A relaxation phenomenon due to the m=2 mode is newly observed in Ohmic plasmas

Effects of liraglutide on cardiovascular outcomes in type 2 diabetes patients with and without baseline metformin use: Post hoc analyses of the LEADER trial

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce cardiovascular (CV) events among patients with type 2 diabetes and high CV risk. Because consensus professional society recommendations endorse metformin as the first-line medication for type 2 diabetes, the CV efficacy of GLP-1RAs has primarily been studied with background metformin therapy. However, the European Society of Cardiology now recommends GLP-1RAs as a first-line type 2 diabetes treatment for patients at high CV risk. These discordant recommendations raise the question of how background metformin might influence the CV benefits of GLP-1RAs. Using data from the LEADER trial,we sought to answer this question by exploring possible heterogeneity in the CV efficacy of liraglutide related to baseline metformin treatment

Green functions for generalized point interactions in 1D: A scattering approach

Recently, general point interactions in one dimension has been used to model a large number of different phenomena in quantum mechanics. Such potentials, however, requires some sort of regularization to lead to meaningful results. The usual ways to do so rely on technicalities which may hide important physical aspects of the problem. In this work we present a new method to calculate the exact Green functions for general point interactions in 1D. Our approach differs from previous ones because it is based only on physical quantities, namely, the scattering coefficients, $R$ and $T$, to construct $G$. Renormalization or particular mathematical prescriptions are not invoked. The simple formulation of the method makes it easy to extend to more general contexts, such as for lattices of $N$ general point interactions; on a line; on a half-line; under periodic boundary conditions; and confined in a box.Comment: Revtex, 9 pages, 3 EPS figures. To be published in PR

Improved time in range and glycemic variability with sotagliflozin in combination with insulin in adults with type 1 diabetes: A pooled analysis of 24-week continuous glucose monitoring data from the IntanDEM program

OBJECTIVE To evaluate effects of the dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibitor sotagliflozin in combination with insulin on glucose time in range (TIR) and glucose excursions, postprandial glucose (PPG), and other glycemic metrics in adults with type 1 diabetes using masked continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS Data sets from the inTandem1 (clinical trial reg. no. NCT02384941) and inTandem2 (clinical trial reg. no. NCT02421510) double-blind randomized trials evaluating sotagliflozin versus placebo in adults with type 1 diabetes treated with optimized insulin were pooled for analyses of masked CGM data from a subset of participants in each trial. The pooled cohort included patients randomized to receive placebo (n = 93), sotagliflozin 200 mg (n = 89), or sotagliflozin 400 mg (n = 96). The primary outcome was change from baseline to week 24 in glucose TIR (3.9–10.0 mmol/L [70–180 mg/dL]). Secondary end points included time below and above the target range and 2-h PPG level assessed after a standardized mixed meal. RESULTS Mean percentage of glucose TIR/percentage time spent at <3.9 mmol/L (<70 mg/dL) during week 24 was 51.6%/5.9%, 57.8%/5.5%, and 64.2%/5.5% with placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively, which corresponded to a placebo-adjusted change from a baseline of +5.4%/20.3% (P = 0.026; +1.3/20.1 h/day) for sotagliflozin 200 mg and +11.7%/20.1% (P < 0.001; +2.8/20.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 6 0.7 mmol/L (35 6 13 mg/dL; P = 0.004) and 2.8 6 0.7 mmol/L (50 6 13 mg/dL; P < 0.001) with sotagliflozin 200 and 400 mg, respectively. CONCLUSIONS Combined with optimized insulin in type 1 diabetes, sotagliflozin significantly increased glucose TIR without increasing time spent at <3.9 mmol/L and reduced PPG, thereby improving glycemic control

Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial

Aims: Whether glycaemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated haemoglobin (HbA1c) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. Methods and results: Secondary analysis of 14 656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (interquartile range 2.3–3.8) year follow-up, 456 (3.1% of 14 656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted hazard ratio (HR) of 1.21 [95% confidence interval (CI) 1.11–1.33] for first HF hospitalization, 1.11 (1.03–1.21) for all-cause death, 1.18 (1.09–1.26) for death or HF hospitalization, and 1.10 (1.02–1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12–1.64) for first HF hospitalization, 1.37 (1.16–1.61) for death, 1.42 (1.23–1.64) for death or HF hospitalization, and 1.22 (1.06–1.41) for non-HF cardiovascular events. Conclusion: Glycated haemogobin exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00790205

Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials

35 and ≥35 kg/m2), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both25, ≥25-&ltAssociations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25-<30, ≥30-<35 and ≥35 kg/m2), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; Pinteraction =.02); otherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed.therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (&ltAssociations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertainPinteraction =.02)30, ≥30-&ltotherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed

Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes: Secondary Analysis (DEVOTE 11)

Introduction: The associations of chronic kidney disease (CKD) severity, cardiovascular disease (CVD), and insulin with the risks of major adverse cardiovascular events (MACE), mortality, and severe hypoglycemia in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk are not known. This secondary, pooled analysis of data from the DEVOTE trial examined whether baseline glomerular filtration rate (GFR) categories were associated with a higher risk of these outcomes. Methods: DEVOTE was a treat-to-target, double-blind trial involving 7637 patients with T2D at high CV risk who were randomized to once-daily treatment with either insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). Patients with estimated GFR data at baseline (n = 7522) were analyzed following stratification into four GFR categories. Results: The risks of MACE, CV death, and all-cause mortality increased with worsening baseline GFR category (P < 0.05), with a trend towards higher rates of severe hypoglycemia. Patients with prior CVD, CKD (estimated GFR < 60 mL/min/m2), or both were at higher risk of MACE, CV death, and all-cause mortality. Only CKD was associated with a higher rate of severe hypoglycemia, and the risk of MACE was higher in patients with CVD than in those with CKD (P = 0.0003). There were no significant interactions between randomized treatment and GFR category. Conclusion: The risks of MACE, CV death, and all-cause mortality were higher with lower baseline GFR and with prior CVD, CKD, or both. The relative effects of degludec versus glargine U100 on outcomes were consistent across baseline GFR categories, suggesting that the lower rate of severe hypoglycemia associated with degludec use versus glargine U100 use was independent of baseline GFR category. Funding: Novo Nordisk

Hypertension Control in Adults with Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function

Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)

Aims: The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older. Materials and methods: A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs). Results: Patients with increasing age had higher risks of CV death, all-cause mortality and SAEs, and there were non-significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all-cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non-significant interactions between treatment and age with regard to these outcomes. Conclusions: There were higher risks of CV death, all-cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all-cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all-cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age

Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: The North American in Tandem1 study

OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The in Tandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400mg(n =262) after6 weeks ofinsulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks. RESULTS: From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P &lt; 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c &lt;7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were 21.08 mmol/L for fasting plasma glucose, 24.32 kg for weight, and 215.63% for bolus insulin dose and 211.87% for basal insulin dose (all P &lt; 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P &lt; 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo. CONCLUSIONS: In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941)