Non-traditional Cardiovascular Risk Factors in DM type 2

描述 (申请人摘要)2型糖尿病的主要后果 (DM 2)是动脉粥样硬化相关疾病的加速发展。 传统的心血管危险因素(CVRF)只能解释一部分 在这一人群中存在动脉粥样硬化的额外风险。这个项目的总体目标是 项目是测试新的CVRF是否与存在和 2型糖尿病患者动脉粥样硬化和大血管事件的发展 确定强化降糖治疗是否会降低 这些CVRF。具体的短期主要目标包括确定交叉- 基线水平与动脉粥样硬化的存在之间的分段关系 电子束CT测量的硬化症 冠状动脉(CAC)和腹主动脉钙(AAC)及其患病率 临床大血管疾病。调查员提议利用 “血糖”V-A协作性研究的研究对象和框架 DM 2中的控制和并发症以有效的方式解决这些问题 并且性价比高的方式。合作研究是一项前瞻性、双臂、 随机、对照、多中心试验，以评估TECH的效果 血糖控制，通过强化治疗实现，对临床 2型糖尿病患者的大血管和微血管并发症 尽管进行了药物治疗，但血糖控制不佳。合作学习 来自多个站点的受试者(340名受试者)将被要求参与 这次额外的审判。在他们的基线访问中，受试者将有额外的 采集血液和尿液，用于a)极低密度脂蛋白、低密度脂蛋白和低密度脂蛋白亚组分b)测量 体内氧化应激(氧化磷脂对血浆低密度脂蛋白、自身抗体的影响 氧化低密度脂蛋白的表位，F2-异前列腺素水平)c)年龄-低密度脂蛋白水平，以及 D)内皮细胞活化/损伤标志物(PAI-1、VCAM-1和ICAM-1)和 炎症(C反应蛋白和纤维蛋白原)。受试者也将有CAC 瑞声科技决定。登记参加这项研究后，参与者将拥有 6个月后重复测量CVRF。主要和次要 大血管终点将与VA中定义的大血管终点相同 合作研究(主要：心肌梗死、心血管死亡、 中风、充血性心力衰竭、侵入性血管治疗(冠状动脉或 外周)，因缺血性坏疽而截肢；继发性：心绞痛 心脏病、短暂性脑缺血发作和外周动脉疾病)。 统计方法，根据具体目的，将包括分类 经年龄和性别调整的分析、t检验和多元回归模型。长- 长期(未来)目标将包括评估 这些新的心血管危险因素与动脉粥样硬化的进展 以及大血管疾病在同一人群中的发展。

DESCRIPTION (Applicant's Abstract) A predominant consequence of diabetes mellitus type 2 (DM 2) is accelerated development of atherosclerosis related conditions. Conventional cardiovascular risk factors (CVRF) only explain a portion of the excess risk for atherosclerosis in this population. The overall goals of this project are to test whether novel CVRF are related to the presence and development of atherosclerosis and macrovascular events in DM 2 and to determine whether intensive glucose lowering therapy will reduce the levels of these CVRF. Specific short-term primary aims include determining the cross- sectional relationship between baseline levels and the presence of athero- sclerosis as measured by electron beam computed tomography assessment of coronary artery (CAC) and abdominal aortic calcium (AAC) and the prevalence of clinical macrovascular disease. The investigator proposes to take advantage of the study population and framework of the V A Cooperative study of "Glycemic Control and Complications in DM 2" to address these questions in an efficient and cost-effective manner. The Cooperative study is a prospective, two-arm, randomized, controlled, multicenter trial to assess the effects of tight glycemic control, achieved through intensification of treatment, on clinical macrovascular and microvascular complications in patients with DM 2 who are in poor glycemic control despite pharmacologic therapy. Cooperative study subjects from multiple sites (340 subjects) will be asked to participate in this additional trial. At their baseline visit, subjects will have additional blood and urine collected for a) VLDL, IDL and LDL subfractions b) measures of in vivo oxidative stress (oxidized-phospholipids on plasma LDL, autoantibodies to epitopes of oxidized LDL, F2-isoprostane levels) c) AGE-LDL levels, and d) markers of endothelial activation/injury (PAI-1, VCAM-1 and ICAM-1) and inflammation (C-reactive protein and fibrinogen). Subjects will also have CAC and AAC determined. After enrollment in the study, participants will have measurements of CVRF repeated at six months. Primary and secondary macrovascular endpoints will be identical to those defined in the VA Cooperative study (Primary: myocardial infarction, cardiovascular death, stroke, congestive heart failure, invasive vascular therapy (coronary or peripheral), and amputation due to ischemic gangrene; Secondary: angina pectoris, transient ischemic attacks, and peripheral artery disease). Statistical methods, depending on the specific aim will include categorical age and sex adjusted analyses, t-tests, and multiple regression models. Long- term (future) aims will include evaluating the prospective relationship of these novel cardiovascular risk factors to the progression of atherosclerosis and the development of macrovascular disease in this same population.