INSULIN, INSULIN RESISTANCE, HYPERGLYCEMIA AND CARDIOVAS

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）。 这可能是由于典型的代谢紊乱， 糖尿病、血小板功能和凝血机制障碍，以及 高血压 然而，NIDDM患者心血管疾病过度风险的主要部分 不能归因于糖尿病本身，因为风险先于 与高血糖程度无关。 因为 胰岛素抵抗是NIDDM的主要原因， 对于显性糖尿病，假设胰岛素抵抗，本身， 和/或高胰岛素血症，其特征在于没有充分的胰岛素抵抗， 糖尿病可能是导致CVD的因素， 有NIDDM风险的人。 本申请适用于中心实验室设施， NIH合作协议请求（RFA NIH-91-HL-03-P）。 是 与外地中心合作提交的申请还提交了 来自南加州大学（M. Saad，P.I.）。在这 应用，我们建议进行一系列测量， 确定胰岛素抵抗和心血管疾病的程度 1600名特定领域受试者中的危险因素 中心. 在本申请中，我们提出形成两个核： 分析核心，进行一系列的生化测量，以及 动力学分析核心，用于计算胰岛素敏感性（SI）和血糖 有效性（SG）。 这个实验室构思， 验证并开发了最小模型方法， 用于评估胰岛素敏感性（即，电阻）。 测定将 在南加州大学的4个实验室进行：Bergman（胰岛素，葡萄糖， C肽）、Meiselman（血液和血浆粘度、红细胞 聚集、ζ沉降率和血液学指标）， 弗朗西斯（纤维蛋白原，因子VIIc，纤溶酶原激活物抑制剂a， 凝血酶原因子F1.2和纤维蛋白D-二聚体片段）。 此外，本发明还提供了一种方法， 心血管疾病的脂蛋白危险因素将由Dr. 芭芭拉霍华德和琳达柯蒂斯医生。 此外，我们还提出了一个 动力学分析核心，它将从我们的检测中计算SI和SG 结果 最小模型计算还将与 用不同的软件计算相同的参数。 结果进行 决定将以电子方式传送给协调 分析中心。 据信，该组合的测定/动力学 分析设施将提供一个高效，准确和精确的 评估不同受试者组中的胰岛素抵抗， 这将产生对胰岛素重要性的准确评估 抵抗和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.