CRP AND ADIPONECTIN AS MARKERS FOR INSULIN RESISTANCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该研究的目的是确定诸如高灵敏度c反应蛋白（Hs CRP）和脂联素等生物标志物是否可用于非糖尿病、肥胖和非肥胖的非裔美国人（AA）和高加索美国人（CA）的胰岛素抵抗（IR）临床有用的检测。IR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，IR与多种疾病有很强的相关性，包括血管疾病（如高血压、冠心病和CVA）、血脂异常、糖尿病（DM）、全身性炎症和动脉粥样硬化。虽然IR可以通过多种方法测量，但对于IR的诊断没有明确的界限，并且大多数方法难以应用于日常临床实践，特别是门诊护理环境。在这个项目中，我们假设CRP与肥胖和IR（一种“促炎”状态）呈正相关，而脂联素与非糖尿病AA和CA的肥胖和IR呈负相关。临床有用的生物标志物指标，如CRP和脂联素，在两个民族人群中的预测价值是不同的。该研究的具体目的是：1)在亚特兰大地铁地区随机确定的非糖尿病、肥胖和非肥胖的AA和CA组成的人群样本中，通过简单的IR（如HOMA）测定CRP和脂联素血浆水平之间的关系。2)检验CRP和脂联素血浆水平与IR之间的关系在AA和CA中不同的假设。3)利用ROC分析确定CRP或脂联素水平的切点，以区分每个种族/民族中临床显著和非显著IR的受试者。4)在临床研究中心的对照设置中，通过使用频繁采样的静脉葡萄糖耐量试验（FSIGT），进行一项试点验证研究，以测试CRP和脂联素对IR的预测价值。本研究可能有助于使用简化的实用方法对IR患者进行早期识别。这将有助于我们为冠心病、CVA和DM的一级预防制定新的策略。旨在改善IR的干预措施可能为降低CVA和DM的发病率和死亡率提供额外的治疗益处。

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.