CRP AND ADIPONECTIN AS MARKERS FOR INSULIN RESISTANCE

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。本研究的目的是确定高敏C反应蛋白(HS CRP)和脂联素等生物标记物是否可以作为非糖尿病、肥胖和非肥胖非裔美国人(AA)和高加索美国人(CA)的胰岛素抵抗(IR)的临床有用的检测手段。胰岛素抵抗是一种细胞不能正确使用胰岛素的疾病。实验和流行病学研究表明，胰岛素抵抗与多种疾病密切相关，包括血管疾病(如高血压、冠心病和哮喘)、血脂异常、糖尿病(DM)、全身炎症和动脉粥样硬化。虽然IR可以通过多种方法来测量，但对于IR的诊断没有明确的界限，而且大多数方法很难在日常临床实践中应用，特别是在门诊护理环境中。在这个项目中，我们假设在非糖尿病的AA和CA中，CRP与肥胖和IR(一种促炎状态)呈正相关，而脂联素与肥胖和IR呈负相关。临床有用的生物标志物指标，如C反应蛋白和脂联素，在两个民族人群中的预测价值不同。本研究的具体目的是：1)在亚特兰大市区随机抽取由AA和CA组成的非糖尿病、肥胖者和非肥胖者作为样本，用简单的IR法(如HOMA)建立CRP和脂联素血浆水平之间的关系。2)检验AA和CA患者中CRP和脂联素水平与IR的关系是否存在差异。3)利用ROC分析确定C反应蛋白或脂联素水平的临界点，以区分每个种族/民族中具有临床意义和无意义胰岛素抵抗的受试者。4)在临床研究中心受控的人群样本子集中，通过使用频繁采样静脉葡萄糖耐量试验(FSIGT)，进行一项试验性验证研究，以测试CRP和脂联素对IR的预测价值。这项研究可能导致使用简化的实用方法来早期识别患有IR的个体。这将有助于我们制定新的CHD、CVA和DM一级预防策略。旨在改善IR的干预措施可能会提供额外的治疗益处，以降低CVA和DM的发病率和死亡率。

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. The goal of the study is to determine whether biomarkers such as the high sensitivity C-reactive protein (Hs CRP) and adiponectin can be used as clinically useful assays for insulin resistance (IR) in non-diabetic, obese and non-obese African Americans (AA) and Caucasian Americans (CA). IR is a disorder in which the cells do not use insulin properly. Experimental and epidemiological studies have demonstrated the strong associations among IR and a variety of diseases, including vascular diseases (e.g., hypertension, CHD, and CVA), dys-lipidemia, diabetes (DM), systemic inflammation, and atherogenesis. Although IR can be measured by a variety of methods, there are no clear cut-offs for the diagnosis of IR and most of methods are difficult to apply in daily clinical practice, in particular, for outpatient care settings. In this project, we hypothesize that CRP is positively correlated to adiposity and IR (a ¿pro-inflammatory¿ state) whereas adiponectin is inversely correlated to adiposity and IR in non-diabetic AA and CA. The predictive value of clinically useful biomarker indices, such as CRP and adiponectin, is different in the two ethnic populations. The specific aims of the study are: 1) Establish the relationship between CRP and adiponectin plasma levels with simple assays of IR (eg HOMA) in a randomly ascertained, population-based sample of non-diabetic, obese and non-obese subjects composed of both AA and CA in the metro-Atlanta area. 2) Test the hypothesis that the relationship between CRP and adiponectin plasma levels with IR differs in AA versus CA. 3) Utilize a ROC analysis to determine cut-points for CRP or adiponectin levels that distinguish subjects with clinically significant and non-significant IR in each race/ethnic group. 4) Perform a pilot validation study to test the predictive value of CRP and adiponectin for IR by using the frequently-sampled intravenous glucose tolerance test (FSIGT)) in a subset of our population-based sample in the controlled setting of the Clinical Research Center. This study may lead to the early identification of individuals with IR using simplified practical approach. It will help us to develop new strategies for primary prevention of CHD, CVA, and DM. The interventions aimed at improving IR may provide additional therapeutic benefits to reduce the morbidity and mortality of CVA and DM.