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(T1D)患者的预后有了很大的改善，但其发病率和死亡率仍然远远高于普通人群。研究表明，患有T1 D的人心血管风险增加10倍或更多，特别是冠心病(CAD)。与普通人群一样，TID的CAD可能是不同因素混合而成的结果。美国和欧洲的各种研究已经为TID的CAD的潜在原因提供了一些重要的线索。我们感觉到的主要潜在特征之一是胰岛素抵抗(IR)。在T1D中，IR是冠心病和肾脏疾病的基础，并提供了一个“共同的土壤”，它负责肾脏疾病和CAD之间的大部分联系。糖尿病并发症流行病学研究(EDC)研究糖尿病并发症的患病率、发病率和危险因素已超过16年。研究人群是匹兹堡儿童医院登记处确定的TID患者的明确队列。所有658名基线(1986-1988)的受试者都是在1950-80岁之间确诊的，年龄为17岁。在拟议的项目期间，我们计划在不同程度的肾脏疾病的背景下研究肾脏疾病、IR和CAD之间的相互关系，作为EDC的一个子研究。更具体地说，我们的目标是：鉴定和比较临床有和没有冠心病、肾脏疾病(即正常、微量和大量白蛋白尿)患者的胰岛素抵抗因素；确定估计的胰岛素抵抗(估计的葡萄糖处置速率，eGDR)和/或IR相关因素是否能解释肾脏疾病中过量的CAD；确定由正电子发射断层扫描(PET)确定的IR，是否在患有和不患有CAD的患者中，两者的葡萄糖摄取有显著差异；以及确定有CAD的患者的总谷甾醇浓度是否高于无CAD的患者。我们还计划利用将在本研究期间获得的后续数据集，对可能介导肾脏-CAD糖尿病并发症风险的CAD风险因素进行进一步的统计分析，包括不对称二甲基精氨酸(ADMA)和核磁共振(核磁共振)脂蛋白图谱。这项研究将有助于增进我们对T1D的CAD的认识，并有望导致适当的预防策略。