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Prediction of Cardiomyopathy in Type I Diabetes by MRS

MRS 预测 I 型糖尿病心肌病

基本信息

批准号：
7210705
负责人：
GERALD Michael POHOST
金额：
$ 38.52万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7210705
关键词：
Animals Arteries Atherosclerosis Bioenergetics Blood Vessels Cardiac Cardiomyopathies Chest Pain Cine Magnetic Resonance Imaging Classification Clinical Congestive Heart Failure Consensus Coronary Arteriosclerosis Detection Development Diabetes Mellitus Diabetic Angiopathies Disease Energy Metabolism Energy Supply Exercise Exhibits Experimental Models Functional disorder Heart Diseases Human Hyperglycemia Hypertension Incidence Insulin-Dependent Diabetes Mellitus Invasive Investigation Ischemia Laboratory Animals Magnetic Resonance Spectroscopy Measurement Measures Metabolic Metabolism Modeling Morbidity - disease rate Myocardial Myocardial Infarction Myocardial Ischemia NMR Spectroscopy Numbers Outcome Patient Recruitments Patients Phosphocreatine Phosphorus Rattus Relative (related person)Reporting Rest Risk Factors Series Source Stress Stress Tests Syndrome Test Result Testing Therapeutic Intervention United States Vascular Diseases Ventricular Dysfunction Ventricular Function Woman Work aged base diabetic diabetic cardiomyopathy heart metabolism illness length improved inorganic phosphate insight mortality novel therapeutics programs research study type I diabetic

项目摘要

Description (provided by applicant): Congestive heart failure is a leading cause of morbidity and mortality in the United States and diabetes has been recognized as a major risk factor for the development of this disease. However, there is a lack of consensus regarding the existence of a diabetes-specific cardiomyopathy as well as the importance of vascular and non-vascular alterations in the development of diabetes-related cardiac disease. We recently demonstrated a transient decrease in cardiac phosphocreatine (PCr)/ATP with handgrip stress, indicative of ischemia, in women with chest pain but no artery disease. The most likely explanation for these results was the presence of microvascular disease. Thus, given the sensitivity of changes in bioenergetics to ischemia and the lack of any direct, non-invasive measurements of microvascular disease, we will use 31P-NMR spectroscopy to evaluate the effects of diabetes on cardiac metabolism. Specifically, we will test the hypothesis that patients with diabetes will exhibit reversible, exercise-induced decreases in PCr/ATP and PCr/inorganic phosphate consistent with an imbalance in energy supply and demand. Furthermore, we propose that these changes will be present only in those diabetic patients with evidence of systematic microvascular disease and will be accompanied by evidence of contractile dysfunction as assessed by cine MRI. Finally we anticipate that the observation of metabolic functional abnormalities will be predictive of short- and long-term outcomes. We will test these hypotheses by determining the effects of handgrip exercise on cardiac bioenergetics and cardiac function in diabetic patients with and without evidence of systematic microvascular disease. We will also evaluate the utility of abnormal cardiac bioenergetics and function as predictors for the development of overt cardiac disease in patients with diabetes. Cardiac bioenergetics will be assessed using 31P-NMR spectroscopy at 4.1T and cardiac function will be measured using cine MRI at 1.5T. Type 1 diabetic patients aged 40 and under with a duration of diabetes greater than 10 years will be studied and grouped based on the presence or absence of systemic microangiopathy. These studies will enable us to assess whether the presence of microvessel disease is a prerequisite for the development of cardiac dysfunction in diabetic patients. This investigation will provide an unprecedented insight into the impact of diabetes on cardiac function and bioenergetics in humans. This will provide valuable information for the development of novel therapeutic interventions and improved management of diabetic patients with cardiac disease.

描述(申请人提供)：充血性心力衰竭是主要的在美国，糖尿病的发病率和死亡率一直是被认为是这种疾病发展的主要风险因素。然而，对于糖尿病特异性疾病的存在缺乏共识心肌病以及血管性和非血管性的重要性糖尿病相关心脏病的发展变化。我们最近显示心肌磷酸肌酸(PCr)/ATP的一过性下降有胸痛但没有动脉的女性的手握力应激，表明存在缺血疾病。对这些结果最有可能的解释是微血管疾病。因此，鉴于生物能量学变化的敏感性缺血和缺乏任何直接的，非侵入性的测量对于微血管疾病，我们将使用31P-核磁共振波谱来评估其疗效。糖尿病对心脏代谢的影响。具体地说，我们将检验这个假设糖尿病患者将表现出可逆的运动诱导的减少在聚合酶链式反应/三磷酸腺苷和聚合酶链式反应/无机磷中，与能量失衡一致供求关系。此外，我们建议这些变化将会出现仅限于那些有系统性微血管证据的糖尿病患者疾病，并将伴随收缩功能障碍的证据用电影磁共振成像进行评估。最后我们预计，对新陈代谢的观察功能异常将预示短期和长期结果。我们将通过确定握手练习的效果来检验这些假设糖尿病合并高血压患者心脏生物能量学和心功能的研究没有系统性微血管疾病的证据。我们还将评估异常心脏生物能量学的应用及其作为心脏疾病预测因子的作用糖尿病患者显性心脏病的发生。心脏生物能量学将在4.1T和心脏温度下使用31P-核磁共振波谱进行评估功能将在1.5T时使用电影MRI进行测量。老年1型糖尿病患者糖尿病病程超过10年的40岁及以下患者将被研究并根据是否有全身微血管病变进行分组。这些研究将使我们能够评估微血管疾病的存在是否糖尿病患者发生心功能障碍的先决条件。这项调查将提供前所未有的洞察，了解糖尿病对人类心脏功能和生物能量学的影响。这将提供对开发新的治疗干预措施和改善糖尿病合并心脏病患者的管理。