Progression of Cardiovascular Disease in TID: CADRE/EDC

描述（由申请人提供）： 尽管在过去的50年中，1型糖尿病（T1D）患者的预后有了相当大的改善，但发病率和死亡率仍然大大超过一般人群。研究表明，患有T1D的人的心血管风险增加十倍或更多，特别是来自冠状动脉疾病（CAD）的风险。与一般人群一样，TID中的CAD可能是由不同因素的混合物引起的。美国和欧洲的各种研究已经产生了一些关于TID中CAD的潜在原因的重要线索。我们感觉到的主要潜在特征之一是胰岛素抵抗（IR）。提出IR是T1D中CAD和肾脏疾病的基础，并且提供了负责肾脏疾病和CAD之间的大部分联系的"共同土壤"。糖尿病并发症流行病学研究（EDC）已经检查了16年以上糖尿病并发症的患病率，发病率和危险因素。研究人群是从匹兹堡儿童医院登记处确定的明确定义的TID患者队列。基线（1986 - 1988年）的所有658名受试者均在1950 - 80年之间诊断，年龄<17岁。在拟定项目期间，我们计划在不同程度的肾脏疾病背景下研究肾脏疾病、IR和CAD之间的相互关系，作为EDC的子研究。更具体地说，我们的目标是：在肾脏疾病分层内和跨肾脏疾病分层内，表征并比较有和无临床CAD患者的胰岛素抵抗因素（即正常、微量和大量白蛋白尿）;确定是否考虑估计的胰岛素抵抗（估计的葡萄糖处置率，eGDR）和/或IR相关因素将解释肾脏疾病中的过度CAD;确定IR，如由正电子发射断层扫描（PET）确定的骨骼肌葡萄糖摄取所表示的，在没有肾病和存在肾病的情况下，在具有和不具有CAD的那些中是否显著不同;并确定与没有CAD的人相比，CAD患者中的总谷甾醇浓度是否增加。我们还计划使用本研究期间可用的随访数据集，对可能介导肾脏-CAD糖尿病并发症风险的CAD风险因素（包括不对称二甲基精氨酸（ADMA）和核磁共振（NMR）脂蛋白谱）进行进一步统计分析。这项研究将有助于提高我们对T1D患者CAD的认识，并希望能够制定适当的预防策略。

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.