LIPID BIOMARKERS FOR DIABETIC COMPLICATIONS

描述（由申请人提供）：糖尿病与严重的心血管并发症有关，包括心力衰竭。在动物模型和人类受试者中进行的研究数据表明，脂肪酸代谢的改变，独立于动脉粥样硬化，参与糖尿病心肌病心力衰竭的发病机制。本研究将检验心肌脂肪酸输送和利用过度与2型糖尿病患者心肌病相关的总体假设。此外，我们假设脂质代谢的改变可以用来开发新的生物标志物，用于早期检测心肌脂质暴露和糖尿病心肌病。为了验证这些假设，我们将研究脂肪酸代谢，脂质生物标志物和心脏功能之间的关系，在仔细表征的男性和女性谁跨越生理和病理生理范围的胰岛素敏感性，血脂生物标志物和心脏功能。本研究的目的是：1）鉴定用于早期检测和管理糖尿病心肌病的新型血浆生物标志物; 2）确定脂肪酸递送至心脏的操作是否影响糖尿病心肌病的功能表现。本研究将有助于更好地了解全身和心肌脂肪酸代谢与心功能的关系，也可能为糖尿病心肌病的诊断、预防和治疗提供新的策略。公共卫生相关性：糖尿病与严重的心血管并发症有关，包括与冠状动脉疾病无关的心力衰竭。科学证据表明，血脂水平可能在这种并发症中起主要作用。我们的研究将调查成人2型糖尿病患者血脂水平和心脏功能之间的联系。我们的目标是开发新的基于血液的糖尿病心脏病生物标志物，并提供新的治疗策略。

DESCRIPTION (provided by applicant): Diabetes is associated with serious cardiovascular complications that include heart failure. Data from studies conducted in animal models and human subjects suggest that alterations in fatty acid metabolism, independent of atherosclerosis, are involved in the pathogenesis of heart failure in diabetic cardiomyopathy. This study will test the overall hypothesis that excessive myocardial fatty acid delivery and utilization is associated with cardiomyopathy in patients who have type 2 diabetes mellitus. Moreover, we hypothesize that alterations in lipid metabolism can be exploited to develop novel biomarkers for early detection of myocardial lipid exposure and diabetic cardiomyopathy. To test these hypotheses, we will study the relationship between fatty acid metabolism, lipid biomarkers and cardiac function in carefully characterized men and women who span physiological and pathophysiological ranges in insulin sensitivity, plasma lipid biomarkers and cardiac function. The goals of this study are to 1) identify novel plasma biomarkers for early detection and management of diabetic cardiomyopathy; and 2) determine whether manipulations of fatty acid delivery to the heart affect the functional manifestations of diabetic cardiomyopathy. This study will provide a better understanding of the relationship between systemic and myocardial fatty acid metabolism and cardiac function, which could also lead to new strategies for diagnosis, prevention, and treatment of diabetic cardiomyopathy. PUBLIC HEALTH RELEVANCE: Diabetes is associated with serious cardiovascular complications including heart failure that is unrelated to coronary artery disease. Scientific evidence suggests that blood fat levels may play a major role in this complication. Our study will investigate the link between blood fat levels and heart function in adults with type 2 diabetes. Our goal is to develop new blood-based biomarkers of heart disease in diabetics and to provide insight into new therapeutic strategies.