Progression of Cardiovascular Disease in TID: CADRE/EDC

TID 中心血管疾病的进展：CADRE/EDC

• 批准号: 6954688
• 负责人: TREVOR J. ORCHARD
• 金额: $ 52.37万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954688
• 关键词: acute phase protein; albuminuria; arginine; biomarker; blood proteins; cardiovascular disorder risk; clinical research; comorbidity; coronary disorder; diabetic nephropathy; glucose transport; human subject; insulin dependent diabetes mellitus; insulin sensitivity /resistance; interleukin 6; interleukin 8; kidney disorder; lipid metabolism; longitudinal human study; pathologic process; patient oriented research; plasminogen activator inhibitors; positron emission tomography; sitosterols; transforming growth factors; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Although the prognosis in patients with Type 1 diabetes (T1D) has improved considerably over the last 50 years, the morbidity and mortality rates still greatly exceed that of the general population. Research has demonstrated that people with T1 D have a ten fold or greater increase in cardiovascular risk, particularly from coronary artery disease (CAD). CAD in TID, as in the general population, is likely to result from an amalgam of different factors. A variety of studies in the United States and Europe have yielded some important clues as to the potential causes of CAD in TID. One of the major underlying features we feel is insulin resistance (IR). It is proposed that IR underlies both CAD and renal disease in T1D and provides a "common soil" which is responsible for much of the link between renal disease and CAD. The Epidemiology of Diabetes Complications Study (EDC) has examined the prevalence, incidence, and risk factors contributing to diabetes complications for over 16 years. The study population is a well-defined cohort of TID patients identified from the Children's Hospital of Pittsburgh registry. All 658 examined subjects at baseline (1986-1988) were diagnosed between 1950-80 at age <17 years. During the proposed project period, we plan to study the interrelationships between renal disease, IR and CAD in the context of various degrees of renal disease as a substudy of EDC. More specifically we aim to: characterize and compare insulin resistance factors of those with and without clinical CAD, within and across strata of renal disease (i.e. normal, micro, and macroalbuminuria); determine if accounting for estimated insulin resistance (estimated glucose disposal rate, eGDR) and/or IR related factors will explain the excess CAD in renal disease; determine if IR, as represented by positron emission tomography (PET) determined skeletal muscle glucose uptake, differs significantly in those with and without CAD both, in the absence of renal disease and in the presence of nephropathy; and to determine if total sitosterol concentration is increased in those with CAD compared to those without CAD. We also plan to conduct further statistical analyses of CAD risk factors that may mediate the renal- CAD diabetes complications risk, including asymmetric dimethylarginine (ADMA) and Nuclear Magnetic Resonance (NMR) lipoprotein profile, using the follow up data set that will become available during this study period. This study will help advance our knowledge of CAD in T1D and hopefully lead to appropriate preventative strategies.

描述（由申请人提供）： 尽管在过去的50年中，1型糖尿病患者（T1D）患者的预后有了很大改善，但发病率和死亡率仍然大大超过了普通人群。研究表明，患有T1 D的人的心血管风险有十倍或更大的增加，尤其是冠状动脉疾病（CAD）。像普通人群一样，泰德（Tid）中的CAD可能是由不同因素的汞合金造成的。在美国和欧洲的各种研究都提出了有关TID中CAD的潜在原因的一些重要线索。我们认为的主要基础特征之一是胰岛素抵抗（IR）。有人提出，IR在T1D中均构成了CAD和肾脏疾病的基础，并提供了一种“常见的土壤”，该土壤构成了肾脏疾病与CAD之间的许多联系。糖尿病并发症研究（EDC）的流行病学研究了16年以上导致糖尿病并发症的患病率，发病率和危险因素。该研究人群是从匹兹堡注册中心儿童医院确定的一群定义明确的TID患者队列。在基线（1986-1988）的所有658名受试者（1950 - 80岁）<17岁时都被诊断出。在拟议的项目期间，我们计划在各种肾脏疾病的背景下研究肾脏疾病，IR和CAD之间的相互关系，这是EDC的典型。更具体地说，我们的目的是：表征和比较肾脏疾病层和临床CAD的人的胰岛素抵抗因子（即正常，微藻和大藻）；确定估计胰岛素抵抗（估计的葡萄糖处置率，EGDR）和/或IR相关因素是否会解释肾脏疾病中的过量CAD；确定IR是否由正电子发射断层扫描（PET）确定的骨骼肌葡萄糖摄取所代表，在没有CAD的情况下，在没有肾脏疾病的情况下和存在肾病的情况下，IR是否有明显不同。并确定与没有CAD相比，CAD的静态浓度是否升高。我们还计划对CAD危险因素进行进一步的统计分析，以介导肾脏CAD糖尿病并发症风险，包括不对称的二甲基精氨酸（ADMA）和核磁共振（NMR）脂蛋白谱，使用后续数据集在本研究期间可用。这项研究将有助于提高我们对T1D中CAD的了解，并希望导致适当的预防策略。