In Vivo Evaluation of Myocardial Lipids

心肌脂质的体内评估

• 批准号: 7102790
• 负责人: LIDIA S SZCZEPANIAK
• 金额: $ 13.06万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102790
• 关键词: adipose tissue; clinical research; diabetes mellitus therapy; glucose tolerance; glyburide; heart function; heart imaging /visualization /scanning; human subject; human therapy evaluation; hypoglycemic agents; insulin sensitivity /resistance; magnetic resonance imaging; myocardium; noninsulin dependent diabetes mellitus; obesity; patient oriented research; rosiglitazone

DESCRIPTION (provided by applicant): As we have became the fattest nation in the world, obesity is an increasingly important cause of myocardial morbidity and mortality in the United States. Obesity indirectly contributes to heart disease by increasing plasma lipids and predisposing to diabetes and hypertension (i.e. traditional cardiovascular risk factors). In addition, recent work from Roger Unger advances the novel hypothesis that obesity per se constitutes a direct cause of left systolic ventricular dysfunction and hypertrophy by promoting cardiac steatosis. Major Hypothesis: Cardiac steatosis is an integral feature of human obesity, contributing to decrease of LV systolic function. I further hypothesize that these functional abnormalities of the human heart are provoked by the development of non-insulin dependent diabetes mellitus (type 2 diabetes) and can be reversed by treatment with Thiazolidinediones. Specific Aims: In human subjects without heart disease, I will measure lipid deposition in the ventricular septum using double gated localized proton nuclear magnetic resonance (1H NMR) as well as LV systolic function with magnetic resonance imaging (MRI) to accomplish the following specific aims: Aim 1: To document the intra-subject reproducibility of the 1H NMR measurement of intra-myocardial lipid content. Aim 2: To establish the relation between adiposity and myocardial lipid deposition over a wide range of BMI and determine the impact of gender, and ethnicity on these relations. Aim 3: To determine if intra-myocardial lipid deposition is greater in individuals with IGT and insulin resistance than in these with normal glucose tolerance matched for BMI, age, gender and ethnicity. I hypothesize that the greater myocardial lipid in diabetic and prediabetic individuals will be accompanied by decreased LV systolic function. Aim 4: To perform randomized prospective study to test the hypothesis that the elevated myocardial lipid content and decreased systolic LV function can be reversed or minimized by the treatment with Thiazolidinediones. In contrast, I predict that functional cardiac abnormalities will be unaffected when diabetic subjects are treated with sulfonylureases that have no effect on PPAR-gamma.

描述（由申请人提供）： 随着我们成为世界上最肥胖的国家，肥胖是美国心肌病发病率和死亡率的一个日益重要的原因。肥胖通过增加血脂和诱发糖尿病和高血压（即传统的心血管风险因素）间接导致心脏病。此外，Roger Unger最近的工作提出了一个新的假设，即肥胖本身通过促进心脏脂肪变性而构成左收缩心室功能障碍和肥大的直接原因。 主要假设：心脏脂肪变性是人类肥胖的一个重要特征，导致LV收缩功能下降。我进一步假设，这些人类心脏功能异常是由非胰岛素依赖型糖尿病（2型糖尿病）的发展引起的，并且可以通过噻唑烷二酮类药物治疗逆转。 具体目标：在无心脏病的人类受试者中，我将使用双门控局部质子核磁共振（1H NMR）测量室间隔中的脂质沉积，以及使用磁共振成像（MRI）测量LV收缩功能，以实现以下特定目标： 目的1：记录1H NMR测量心肌内脂质含量的受试者内重现性。 目标二：在广泛的BMI范围内建立肥胖与心肌脂质沉积之间的关系，并确定性别和种族对这些关系的影响。 目标3：确定IGT和胰岛素抵抗个体的心肌内脂质沉积是否大于BMI、年龄、性别和种族匹配的正常葡萄糖耐量个体。我推测糖尿病和糖尿病前期个体的心肌脂质增加将伴随着左室收缩功能下降。 目标4：进行随机前瞻性研究，以验证噻唑烷二酮类药物治疗可逆转或最小化心肌脂质含量升高和左室收缩功能降低的假设。与此相反，我预测，功能性心脏异常将不受影响时，糖尿病受试者与磺酰脲酶治疗，对PPAR-gamma没有影响。