Prediction of Cardiomyopathy in Type I Diabetes by MRS

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 被认为是发生这种疾病的主要危险因素。然而， 对于糖尿病特异性的存在缺乏共识 心肌病以及血管性和非血管性心肌病的重要性 糖尿病相关心脏病发展的改变。我们最近 证明心脏磷酸肌酸 (PCr)/ATP 短暂降低 对于有胸痛但没有动脉的女性，握力表示缺血 疾病。对这些结果最可能的解释是存在 微血管疾病。因此，考虑到生物能学变化的敏感性 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31P-NMR波谱来评估效果 糖尿病对心脏代谢的影响。具体来说，我们将检验假设 糖尿病患者会表现出可逆的、运动引起的下降 PCr/ATP 和 PCr/无机磷酸盐与能量不平衡一致 供给和需求。此外，我们建议这些变化将会出现 仅适用于有系统性微血管病变证据的糖尿病患者 疾病，并伴有收缩功能障碍的证据，如 通过电影 MRI 进行评估。最后我们预计代谢的观察 功能异常将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 糖尿病患者心脏生物能学和心功能的研究 无系统性微血管疾病的证据。我们还将评估 异常心脏生物能学和功能作为预测因子的效用 糖尿病患者出现明显的心脏病。心脏 将使用 4.1T 的 31P-NMR 波谱法和心脏功能来评估生物能学 功能将使用 1.5T 的电影 MRI 进行测量。 1型糖尿病患者年龄 将研究糖尿病病程超过 10 年的 40 岁及以下人群 并根据是否存在全身性微血管病进行分组。这些 研究将使我们能够评估微血管疾病的存在是否与 是糖尿病患者发生心功能障碍的先决条件。 这项调查将为我们提供前所未有的洞察力 糖尿病对人类心脏功能和生物能学的影响。这将提供 对于开发新型治疗干预措施和 改善糖尿病合并心脏病患者的管理。

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.