Prediction of Cardiomyopathy in Type I Diabetes by MRS

MRS 预测 I 型糖尿病心肌病

• 批准号: 6610198
• 负责人: GERALD Michael POHOST
• 金额: $ 39.73万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6610198
• 关键词: adenosine triphosphate; bioenergetics; bioimaging /biomedical imaging; creatine phosphate; diabetic angiopathy; diabetic cardiomyopathy; disease /disorder etiology; exercise; heart imaging /visualization /scanning; heart metabolism; human subject; insulin dependent diabetes mellitus; nuclear magnetic resonance spectroscopy; pathologic process; patient oriented research; young adult human (21-34)

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（由申请人提供）：充血性心力衰竭是一种主要的 糖尿病是美国发病率和死亡率的主要原因， 被认为是这种疾病发展的主要危险因素。然而，在这方面， 关于是否存在糖尿病特异性 心肌病以及血管和非血管 糖尿病相关心脏病发展的改变。我们最近 证明了心脏磷酸肌酸（PCr）/ATP的一过性降低， 在胸痛但无动脉的女性中，握力提示缺血 疾病对这些结果最可能的解释是 微血管疾病因此，考虑到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， 微血管疾病，我们将使用31 P-NMR光谱来评估效果 对心脏代谢的影响。具体来说，我们将测试假设 糖尿病患者会表现出可逆的，运动引起的 在PCr/ATP和PCr/无机磷酸盐中与能量不平衡一致 供求关系此外，我们建议，这些变化将存在于 仅在有系统性微血管病变证据的糖尿病患者中， 疾病，并将伴随着收缩功能障碍的证据， 通过电影MRI评估。最后我们预计代谢的观察 功能异常可预测短期和长期结果。 我们将通过确定握力练习的效果来检验这些假设 对糖尿病患者心脏生物能量学和心脏功能的影响， 没有系统性微血管疾病的证据我们还将评估 利用异常心脏生物能量学和功能作为 糖尿病患者发生明显心脏病。心脏 生物能量学将使用4.1T下的31 P-NMR光谱进行评估， 将使用1.5T的电影MRI测量功能。老年1型糖尿病患者 将研究40岁及以下、糖尿病病程超过10年的患者 并根据有无全身性微血管病进行分组。这些 研究将使我们能够评估是否存在微血管疾病， 糖尿病患者心功能不全的先决条件。 这项调查将提供一个前所未有的洞察力的影响， 糖尿病对人类心脏功能和生物能量学的影响。这将提供 为开发新的治疗干预措施提供有价值的信息， 改善糖尿病合并心脏病患者的管理。