scholarly journals Effect of Empagliflozin on Endothelial Function in Patients With Type 2 Diabetes and Cardiovascular Disease: Results from the Multicenter, Randomized, Placebo-Controlled, Double-Blind EMBLEM Trial

Diabetes Care ◽  
2019 ◽  
Vol 42 (10) ◽  
pp. e159-e161 ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Noritaka Machii ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Double Blind

Sitagliptin improves vascular endothelial function in Japanese type 2 diabetes patients without cardiovascular disease

2012 ◽  
Vol 02 (03) ◽  
pp. 338-345 ◽  
Author(s):  
Kazunari Suzuki ◽  
Kentaro Watanabe ◽  
Tatsuya Suzuki ◽  
Motoshi Ouchi ◽  
Shoko Futami-Suda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Diabetes Patients

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

scholarly journals Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes: The Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial

Diabetes Care ◽  
2002 ◽  
Vol 25 (7) ◽  
pp. 1211-1216 ◽  
Author(s):  
F. V. van Venrooij ◽  
M. A. van de Ree ◽  
M. L. Bots ◽  
R. P. Stolk ◽  
M. V. Huisman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Function ◽  
Controlled Trial ◽  
Lipid Lowering ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Endothelial function in men with type 2 diabetes without clinical signs of cardiovascular disease

2016 ◽  
Vol 19 (5) ◽  
pp. 383-387 ◽  
Author(s):  
Irina Alexandrovna Khripun ◽  
Sergey Vladislavovich Vorobyev ◽  
Maxim Nikolaevich Morgunov ◽  
Michail Iosifovich Kogan
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Reactive Hyperemia ◽  
Clinical Signs ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Group 2 ◽  
Group 1

Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease that is based on endothelial dysfunction (ED). Currently, conventional diagnostic methods are unreliable, especially at early stages of disease.Aims. The aim of this work was to assess endothelial function in men with T2DM without clinical signs of cardiovascular disease.Materials and methods. The study included 100 patients (mean age, 54.3 ± 5.3 years) with a T2DM duration of less than 10 years and without signs of cardiovascular disease. The patients were divided into two groups: group 1 consisted of 60 patients with a T2DM duration of less than five years. Group 2 included 40 men with a history of diabetes between 5 and 10 years. Endothelial function was assessed by the levels of nitric oxide (NO), endothelial NO synthase type 3 (eNOS3), ICAM-1, VCAM-1, E-selectin, P-selectin, resistin and C-reactive protein and the arterial vasoreactivity of the brachial artery (BA) using the D. Celermajer method.Results. Results revealed decreases in levels of both eNOS3 by 2.5 fold (P = 0.0005) and NO by 1.9 fold (P = 0.043) in group 2 patients, compared to those in group 1 patients. When the duration of diabetes was greater than five years, levels of VCAM-1, resistin and C-reactive protein increased by 12.1% (P = 0.048), 62% (P = 0.01) and 45.6%, respectively. Additionally, the time until maximal BA vasodilatation during reactive hyperemia was observed to be higher in group 2 [105 (90; 180) seconds] than those in group 1 [90 (60; 120) seconds].Conclusions. Biochemical and imaging signs of ED begin to appear in the first five years of T2DM, long before clinical manifestations. The earliest symptoms are decreases in eNOS3 and NO levels, increases in VCAM-1 and resistin concentrations and increased time until maximal BA vasodilatation during reactive hyperemia.

scholarly journals 459 Evaluation of LDL-C reductions by siRNA treatment with inclisiran in patients with diabetes mellitus, metabolic syndrome or neither

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
R. Scott Wright ◽  
David Kallend ◽  
Kausik K Ray ◽  
Lawrence Leiter ◽  
Wolfgang Koenig ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Controlled Trial ◽  
Atherosclerotic Cardiovascular Disease ◽  
Double Blind ◽  
Sirna Treatment ◽  
Patients With Diabetes

Abstract Aims Patients with diabetes (DM) and metabolic syndrome (MS) have elevated risks for atherosclerotic cardiovascular disease (ASCVD). Aggressive LDL-C lowering reduces risks. Inclisiran, a new siRNA, lowers LDL-C and was evaluated in patients with Type 2 diabetes (DM), metabolic syndrome (MS) without DM or neither (N) in the ORION-10 trial. Methods ORION-10 was a double-blind, randomized, placebo controlled trial evaluating inclisiran in 1561 patients with ASCVD on maximally tolerated therapy for lowering LDL-C. 781 inclisiran (INC) participants and 780 placebo (P) patients received 1.5 mL SQ tx at Days 1, 90, then every 6 months until Day 540. We evaluated the time adjusted change in LDL-C from baseline after Days 90–540 in DM (n = 702), MS (n = 455) and N participants (n = 404). Results There were no differences in baseline demographics and background therapies between INC and P. Statins were utilized in 89.8% INC and 88.7% of P. High intensity statins were utilized in 67.2% of INC and 68.8% of P; ezetimibe in 10.2% of NC and 9.5% of P participants. INC reduced LDL-C by − 54.4% (−58.3, −50.6 95% CI) in DM, (P &lt; 0.001), −58.6% (−62.3, −54.8), P &lt; 0.001 in-MS and −56.0% (−60.2, −51.7), in N subjects P &lt; 0.001 (see Figure). Conclusions Inclisiran potently and durably reduces LDL-C across patients with DM, MS and those with neither, demonstrating potent efficacy and durability across glycaemic categories. Inclisiran may also represent a potent LDL-C lowering treatment for those with DM and MS.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

scholarly journals The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease

Diabetes Care ◽  
2005 ◽  
Vol 28 (7) ◽  
pp. 1668-1674 ◽  
Author(s):  
E. D. Beishuizen ◽  
J. T. Tamsma ◽  
J. W. Jukema ◽  
M. A. van de Ree ◽  
J. C. M. van der Vijver ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Statin Therapy

scholarly journals Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Gilles R. Dagenais ◽  
Lars Rydén ◽  
Lawrence A. Leiter ◽  
Mark Lakshmanan ◽  
Leanne Dyal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Double Blind ◽  
Absolute Reduction ◽  
Total Incidence ◽  
Conditional Time ◽  
Time Gap

Abstract Background The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants Methods We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. Results Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028]. Conclusions These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. Clinical Trial Registration:https://www.clinicaltrials.gouv. Unique Identifier NCT01394952).

scholarly journals Endothelial function after 10 days of bed rest in individuals at risk for type 2 diabetes and cardiovascular disease

2011 ◽  
Vol 96 (10) ◽  
pp. 1000-1009 ◽  
Author(s):  
Mette P. Sonne ◽  
Lise Højbjerre ◽  
Amra C. Alibegovic ◽  
Lars B. Nielsen ◽  
Bente Stallknecht ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
At Risk ◽  
Endothelial Function ◽  
Bed Rest
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