INSULIN INSULIN RESISTANCE HYPERGLYCEMIA AND CARDIOVASCU

非胰岛素依赖型糖尿病与风险增加相关 用于冠状动脉周围血管和脑血管疾病 (CVD)。这可以归因于典型的代谢紊乱 糖尿病，血小板功能和凝血机制紊乱，以及 高血压。然而，NIDDM患者心血管疾病超额风险的主要部分 不能归因于糖尿病本身，因为风险先于 NIDDM，与高血糖程度无关。因为 胰岛素抵抗是NIDDM的一个主要原因，而且似乎先于 明显的糖尿病，据推测，胰岛素抵抗本身， 和/或高胰岛素血症，表现为抵抗力不全 暴发性糖尿病可能是心血管疾病的致病因素(S) 有患NIDDM风险的个人。 此应用程序适用于中心实验室设备，并且具有响应能力 NIH合作协议请求(RFA NIH-91-HL-03-P)。它是 与外地中心合作提交的申请也提交了 南加州大学(M.Saad，P.I.)。在这 应用程序，我们建议进行一系列测量，以 确定胰岛素抵抗的程度以及心血管疾病 1600名特定领域受试者的危险因素调查 中锋。在本申请中，我们建议形成两个核心：一个 化验核心，进行一系列生化测量，以及 动力学分析核心，用于计算胰岛素敏感性(SI)和血糖 检测结果的有效性(SG)。这个实验室构思了， 验证并开发了最小模型方法，该方法被提出用于 用于评估胰岛素敏感性(即抵抗力)。化验结果会 在南加州大学的4个实验室进行：伯格曼(胰岛素，葡萄糖， C-肽)、梅塞尔曼(全血和血浆粘度、红细胞 聚集、Zeta沉降率和血液学指标)， Francis(纤维蛋白原，VIIC因子，纤溶酶原激活物抑制物a， 凝血酶原因子F1.2和纤维蛋白D-二聚体片段)。此外, 心血管疾病的脂蛋白风险因素将由Dr。 芭芭拉·霍华德和琳达·柯蒂斯博士。此外，我们还提出了一个 动力学分析核心，它将根据我们的分析计算SI和SG 结果。最小模型计算还将与 相同的参数由不同的软件计算。这些措施的结果 决定将以电子方式传输到协调中心 分析中心。据信，这一结合的分析/动力学 分析设施将提供高效、准确和精确的 评估不同受试者的胰岛素抵抗，以及AS 这将产生对胰岛素重要性的准确评估。 抵抗与高胰岛素血症在心血管疾病发展中的作用 疾病。

Noninsulin dependent diabetes mellitus is associated with increased risk for coronary artery peripheral vascular and cerebrovascular disease (CVD). This could be attributed to metabolic derangements typical of diabetes, disorders of platelet function and coagulation mechanisms, and hypertension. However, the major part of excess risk of CVD in NIDDM cannot be attributed to diabetes per se, because the risk precedes NIDDM, and is uncorrelated with the degree of hyperglycemia. Because insulin resistance is a major cause of NIDDM and appears to precede overt diabetes, it is hypothesized that insulin resistance, per se, and/or the hyperinsulinemia which characterizes resistance without full blown diabetes may be the factor(s) which are responsible for CVD in individuals at risk for NIDDM. This application is for a Central Laboratory Facility, and is responsive to an NIH Request for Cooperative Agreement (RFA NIH-91-HL-03-P). It is submitted in cooperation with a Field Center Application also submitted from the University of Southern California (M. Saad, P.I.). In this application, we propose to make a series of measurements which will establish the degree of insulin resistance as well as cardiovascular risk factors in a group of 1600 subjects to be tested in specific field centers. In this application we propose the formation of two cores: an Assay Core, to carry out a series of biochemical measurements, and a Kinetic Analysis Core, to calculate insulin sensitivity (SI) and glucose effectiveness (SG) from the assay results. This laboratory conceived, validated and developed the minimal model approach which is proposed to be used to assess insulin sensitivity (i.e., resistance). Assays will be performed in 4 laboratories at USC: Bergman (insulin, glucose, C-peptide), Meiselman (blood and plasma viscosity, red blood cell aggregation, zeta sedimentation ratio, and hematological indices), Francis (Fibrinogen, factor VIIc, plasminogen activator inhibitor a, prothrombin factor F1.2, and fibrin D-dimer fragment). In addition, lipoprotein risk factors for CVD will be measured off-site by Dr. Barbara Howard and Dr. Linda Curtiss. Additionally, we propose a Kinetic Analysis Core, which will calculate SI and SG from our assay results. Minimal model calculations will additionally be compared to the same parameters calculated by different software. Results of these determinations will be transferred electronically to a Coordinating Center for analysis. It is believed that this combined Assay/Kinetic Analysis facility will provide an efficient, accurate and precise assessment of insulin resistance in different subject groups, and as such will yield an accurate assessment of the importance of insulin resistance and hyperinsulinemia in the development of cardiovascular disease.