FOREARM ENDOTHELIAL FUNCTION IN NON-INSULIN DEPENDENT DIABETIC PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。2型糖尿病与心血管事件的风险增加有关。高血压和高脂血症等传统的危险因素并不能完全解释这种增加的风险。胰岛素抵抗已成为心血管疾病的独立危险因素，并与许多其他心血管异常有关。尤其是内皮功能似乎与胰岛素的作用密切相关，内皮功能障碍不仅与2型糖尿病患者的胰岛素抵抗有关，而且在肥胖的胰岛素抵抗患者及其亲属中也是如此。因此，胰岛素作用异常可能与内皮功能异常共同遗传。内皮炎症在2型糖尿病和肥胖症患者中也被认为是常见的，最近的证据表明，胰岛素抵抗可能是与胰岛素抵抗受试者炎症标志物升高有关的一个因素。其他与糖尿病心血管疾病相关的非传统危险因素包括凝血和纤溶异常以及同型半胱氨酸升高。如果上述异常确实与胰岛素抵抗有关，那么用直接改善胰岛素敏感性的药物治疗胰岛素抵抗应该会逆转这些异常。曲格列酮的初步数据表明，这些可能的好处包括改善内皮功能，降低胰岛素抵抗动物的血浆同型半胱氨酸，以及几项表明有抗炎作用的研究。由于肝脏毒性问题，曲格列酮已从市场上撤出。没有数据表明，罗格列酮等较新的胰岛素增敏剂没有这种肝脏毒性，并已被证明在改善2型糖尿病患者的血糖控制方面有效。对这些非传统危险因素的有益影响尚未得到证实，尽管初步的动物和体外数据表明，这些好处很可能是一种类别效应。本研究旨在确定罗格列酮(RSG)与阿托伐他汀联合应用是否能改善接受磺脲类药物(SFU)治疗的非胰岛素依赖型糖尿病患者的内皮功能(缺血后的肱动脉血管扩张反应、生化标记物)。这项研究还将旨在确定在上述联合治疗中加用二甲双胍(MET)是否比罗格列酮加阿托伐他汀更有效。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 2 diabetes is associated with an increased risk for cardiovascular events. The traditional risk factors like hypertension and hyperlipidemia do not fully explain this increased risk. Insulin resistance has emerged as an independent risk factor for cardiovascular disease and is associated with a number of other cardiovascular abnormalities. In particular endothelial function appears to be closely related to insulin action and endothelial dysfunction is associated with insulin resistance not only in patients with Type 2 diabetes, but also in obese insulin resistant subjects and their relatives. Thus, it is possible that abnormalities of insulin action are co-inherited with abnormalities of endothelial function. Inflammation of the endothelium is also considered to be common in patients with Type 2 diabetes and obesity and recent evidence suggest that insulin resistance may be a factor that is associated with markers of inflammation being elevated in insulin resistant subjects. Other non-traditional risk factors associated with cardiovascular disease in diabetes include abnormal coagulation and fibrinolysis and elevated homocysteine. If the above abnormalities are indeed associated with insulin resistance then treating insulin resistance with drugs that directly improve insulin sensitivity should reverse these abnormalities. Preliminary data with troglitazone has suggested such possible benefit with improvement in endothelial function, lowering of plasma homocysteine in insulin resistant animals and several studies suggesting an anti-inflammatory effect. Troglitazone was withdrawn from the market due to problems with liver toxicity. There is no data to suggest that the newer insulin sensitizers like rosiglitazone do not have such liver toxicity and have been shown to be effective in improving blood glucose control in patients with Type 2 diabetes. The beneficial effect on these non-traditional risk factors have yet to be demonstrated although preliminary animal and in vitro data suggest that these benefits may well be a class effect. This study will aim to determine if Rosiglitazone (RSG), in combination with Atorvastatin, improves endothelial function (brachial artery vasodilatory response after ischemia, biochemical markers) in non-insulin dependent diabetic patients treated with Sulfonylureas (SFU). The study will also aim to determine if the addition of Metformin (MET) to the above combination is more effective than Rosiglitazone plus Atorvastatin.