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Cholesterol reduction and cardiovascular risk in Type 1 diabetes

1 型糖尿病的胆固醇降低和心血管风险

基本信息

批准号：
10677739
负责人：
Ira J Goldberg
金额：
$ 84.41万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-05 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677739
关键词：
Abnormal Endothelial Cell Acceleration American Heart Association Animal Model Arteries Atherosclerosis Biological Markers Biological Process Blood Platelets Blood Vessels CD8-Positive T-Lymphocytes Cardiovascular Diseases Cardiovascular system Carotid Arteries Characteristics Cholesterol Clinic Clinical Research Clinical Trials Communities Continuous Glucose Monitor Cytometry Data Dendritic Cells Development Diabetes Mellitus Endothelial Cells Epinephrine Event Failure Female Gene Expression Glucose Glycosylated hemoglobin A Harvest Health care facility Impairment Individual Inflammatory Inflammatory Response Insulin-Dependent Diabetes Mellitus LDL Cholesterol Lipoproteins Leukocytes Low-Density Lipoproteins Macrophage Measurement Measures Medical center Methods Natural Killer Cells New York City Non-Insulin-Dependent Diabetes Mellitus PET/CT scan Pathologic Processes Pathway interactions Patient Recruitments Patients Peripheral Blood Mononuclear Cell Platelet aggregation Positron-Emission Tomography Prediction of Response to Therapy Process RNA Research Research Design Residual state Risk Risk Reduction Subgroup Techniques Testing Time Vascular Endothelial Cell Veins Woman abdominal aorta animal data atorvastatin blood glucose regulation cardiovascular disorder risk cardiovascular risk factor experience ezetimibe fluorodeoxyglucose glycemic control human data inflammatory marker inhibitor mRNA sequencing male medical schools men neutrophil platelet function predictive marker prevent process improvement recruit repaired response single-cell RNA sequencing therapeutic target transcriptome treatment response ultrasound underserved community uptake vascular inflammation

项目摘要

ABSTRACT Diabetes markedly increases risk of development of atherosclerotic cardiovascular disease (CVD). Human and animal data also show that diabetes prevents the normal repair of damaged arteries that occurs upon circulating LDL cholesterol (LDL-C) reduction. Because of this, patients with diabetes still have greater risk of a cardiovascular event even after statin reduction of LDL-C than individuals without diabetes. Individuals with diabetes have greater platelet aggregation, altered white blood cells, and more vascular inflammation, pathological processes that are improved by LDL-C reduction in unaffected individuals. We hypothesize that by determining response to LDL-C reduction in T1D, we will identify pathways that can be therapeutically targeted to optimize vascular repair and prevent CVD events. These data can also be used to determine patient characteristics that associate with defective response to LDL-C reduction. We propose a clinical study of response to LDL-C reduction in patients with Type 1 diabetes (T1D). We will recruit the patients from two major medical centers, NYU Langone and Mount Sinai that serve diverse communities within New York City. Subjects will be treated for 4 weeks with robust cholesterol-reducing therapies, PCSK9 inhibitors and also either statin (80 mg atorvastatin) or ezetimibe (10 mg). Each subject will serve as their own control and we will determine changes in platelets and white blood cells along with circulating inflammatory factors that occur when LDL-C is markedly reduced. In a subgroup of subjects, changes in vascular inflammation will be determined by assessment of harvested brachial vein endothelial cells and by uptake of 18F-fluordeoxyglucose into arteries. The data will be analyzed by an experienced statistician with expertise in diabetes and CVD risk and will identify the relationship of these changes with HbA1c and glucose variability, and differences between women and men. In addition, the data in T1D will be compared with similar data assessing response to LDL-C in subjects with Type 2 diabetes and controls to determine abnormalities that differ between these two forms of diabetes.

摘要