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Aims/introduction: To assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics., Materials and Methods: Data from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin-naïve participants) and DUAL II Japan (n = 210 insulin-experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA 1c ; <8.0%, ≥8.0-<9.0%, ≥9.0%), body mass index (<25, ≥25-<30, ≥30 kg/m 2 ) and age (<65, ≥65 years)., Results: In DUAL I Japan, reductions in HbA 1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: -0.48% to -0.72% vs degludec, -0.29% to -0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: -0.82% to -1.61%). Treatment-by-subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA 1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA 1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA 1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment-by-subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan., Conclusions: IDegLira reduced HbA 1c in Japanese participants with type 2 diabetes across baseline HbA 1c , body mass index and age categories, without unexpected safety issues., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: DUAL II Japan (NCT02911948) was a 26-week, phase 3a randomized, treat-to-target trial which compared the efficacy and safety of IDegLira with degludec in 210 Japanese patients with type 2 diabetes (T2D) uncontrolled on premixed or basal insulin therapy. The DUAL II Japan trial presented the opportunity for a post hoc analysis to examine the safety and efficacy of switching patients from a premixed regimen (containing both basal and bolus insulin components) to IDegLira., Methods: Patients from DUAL II Japan were stratified according to prior insulin regimen (premixed or basal insulin). The following endpoints were assessed in this post hoc analysis by pre-trial insulin regimen: change in HbA 1c , body weight, daily total insulin dose, nine-point self-measured blood glucose, and severe or blood glucose-confirmed hypoglycemia (defined as severe or plasma glucose less than 56 mg/dL)., Results: This post hoc analysis included 39 patients who switched from premixed insulin to IDegLira. The treatment effect in this population was independent of insulin type at baseline (premixed or basal; interaction test, P = 0.2535). In patients switching from premixed insulin to IDegLira, mean [standard deviation (SD)] HbA 1c was 8.26% (0.73) at baseline and 6.68% (0.93) at week 26. Mean (SD) body weight was reduced by 1.5 (2.9) kg. At week 26, daily insulin dose was 34.2 dose steps. After 26 weeks, the mean prandial increment was smaller at all meals with IDegLira irrespective of pre-trial insulin regimen. Rate of hypoglycemic events was 2.59 events/patient-year of exposure over the 26 weeks., Conclusion: This post hoc study is the first to evaluate the switch from premixed insulin to IDegLira in patients with uncontrolled T2D. IDegLira initiation resulted in improved HbA 1c and weight loss. This study offers insight into the effectiveness and safety of switching patients from premixed insulin therapy to IDegLira, and provides support for further investigation., Trial Registration: NCT02911948.

In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal-bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal-bolus therapy after 26 weeks of treatment., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Atrial fibrillation (AF) is the most common aberrant cardiac arrhythmia. Many AF patients present with symptoms of dyspnea and fatigue, but have normal left ventricular ejection fraction (LVEF)., Purpose: To determine the reproducibility of measurements of global longitudinal strain (GLS) and strain rate in patients with AF and examine if the arrhythmia is associated with abnormal LV strain and strain rate independent of age, sex, heart rate, LVEF and LV mass. We hypothesized that AF independently reduces ventricular systolic performance., Methods: The study was conducted as a retrospective analysis of images from 150 randomly selected patients with AF compared to an equal number of subjects with sinus rhythm (SR) matched for age, sex, heart rate, LVEF and LV mass. Half of the patients had normal LVEF (LVEF > 50%) and half had reduced LVEF (LVEF < 50%). GLS and strain rate were measured in each group, as were quantitative LV volumes and standard systolic and diastolic parameters. Results: GLS was significantly impaired in patients with AF compared to subjects with SR, both in the overall population (-12.25 ± 4.1% vs. -16.13 ± 4.7%, p<0.0001), in patients with normal LVEF (-14.41 ± 3.9% vs. -19.42 ± 3.1%, p<0.0001) and in patients with reduced LVEF (-10.10 ± 3.1% vs. -12.85 ± 3.5%, p<0.0001).Linear regression and Bland Altman analyses demonstrated good intraobserver and interobserver agreement for measurements of GLS and strain rate parameters even in patients with AF.

Objectives: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated SDF-1α in patients with atrial fibrillation (AF). We aimed to test SDF-1α in a large cohort of patients with AF and its role as a prognostic marker., Design: Between January 1st 2008 to December 1st 2012, 290 patients with ECG documented AF were enrolled from the in- and outpatient clinics at the Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Plasma levels of SDF-1α were measured using ELISA technique. Clinical data were registered and patient follow-up was conducted., Results: Patients with permanent AF had significantly higher SDF-1α levels (2199.5 pg/ml) than the patients with paroxysmal AF (1982.0 pg/ml) and persistent AF (1906.0 pg/ml), p < 0.0005. Higher SDF-1α level was associated with longer time spent in the hospital per readmission, p < 0.05., Conclusion: In AF patients, a higher SDF-1α level was found in patients with a more progressive state of arrhythmia and was associated with longer hospitalizations. These findings suggest that SDF-1α could prove valuable in risk stratification and evaluating the disease burden in AF patients.

Aims: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with substantial morbidity and mortality. AF is associated with enlargement of the left atrium (LA), and the LA volume has important prognostic implications for the disease. The objective of the study was to determine how measurements of LA volume and function obtained by transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and 320-slice multi-detector computed tomography (MDCT) correlate in patients with permanent AF., Methods and Results: Thirty-four patients with permanent AF participated in the study. TTE, CMR, and 320-slice MDCT imaging procedures were performed within 7 ± 4 days. 320-slice MDCT overestimated maximal LA volume (LAmax) and minimal LA volume (LAmin) compared with CMR (LAmax: 80 vs. 73 mL/m(2), P = 0.0017; LAmin: 69 vs. 64 mL/m(2), P = 0.0217), whereas TTE underestimated these parameters compared with CMR (LAmax: 60 vs. 73 mL/m(2), P < 0.0001; LAmin: 50 vs. 64 mL/m(2), P < 0.0001), and also compared with MDCT (LAmax: 60 vs. 80 mL/m(2), P < 0.0001; LAmin: 50 vs. 69 mL/m(2), P < 0.0001). Measurements of LA volumes by MDCT and CMR closely correlated, and both MDCT and CMR had excellent intra- and inter-observer agreement with correlation coefficients of >0.90. The correlation between TTE-derived measurements and CMR/MDCT was fair to moderate. Intra- and inter-observer agreement for LA volume measurements by TTE were inferior to CMR and MDCT., Conclusion: Measurements of LA volumes by CMR and 320-slice MDCT correlate closely in patients with permanent AF, and both modalities improve the reproducibility of measurements of LA volumes and function compared with 2D TTE.

Objective: Left atrial (LA) mechanical function is thought to be virtually inexistent in patients with permanent atrial fibrillation (AF). Due to recent advances in multidetector computed tomography (MDCT) technology, it is now possible to acquire images of the entire heart in a single heartbeat. The objective of this study was to compare individual components of LA function assessed by MDCT in patients with permanent AF and patients in sinus rhythm (SR)., Methods: 320-slice MDCT was performed in 30 patients with permanent AF. Measurements of LA volumes during the cardiac cycle were compared to 30 patients in SR, who were matched with respect to age, sex, left ventricular ejection fraction and body surface area., Results: LA volumes were significantly larger in patients with AF than SR patients at all times during the cardiac cycle (LA maximal volume; 82 vs. 55 ml/m(2), p < 0.0001, LA minimal volume; 71 vs. 30 ml/m(2), p < 0.0001). However, except for the absence of active LA emptying, the overall trend of the LA time-volume curve was similar in patients with AF and SR., Conclusion: Compared to SR patients, patients with permanent AF have significantly increased LA volumes throughout the cardiac cycle. Yet, a residual hemodynamic role of LA function may be maintained during permanent AF., (© 2014 S. Karger AG, Basel.)