CRP AND ADIPONECTIN AS MARKERS FOR INSULIN RESISTANCE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该研究的目的是确定生物标志物，如高敏C反应蛋白（HS CRP）和脂联素是否可用作非糖尿病、肥胖和非肥胖非裔美国人（AA）和高加索美国人（CA）胰岛素抵抗（IR）的临床有用测定。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已经证明了IR和多种疾病之间的强关联，包括血管疾病（例如，高血压、CHD和CVA）、代谢异常、糖尿病（DM）、全身性炎症和动脉粥样硬化形成。虽然IR可以通过多种方法测量，但IR的诊断没有明确的截止值，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（一种促炎症状态）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。临床上有用的生物标志物指标，如CRP和脂联素的预测价值在两个种族人群中是不同的。本研究的具体目的是：1）在亚特兰大大都会地区随机确定的非糖尿病、肥胖和非肥胖受试者（包括AA和CA）的人群样本中，通过简单的IR测定（例如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CRP和脂联素血浆水平与IR之间的关系不同的假设。3)利用ROC分析确定CRP或脂联素水平的临界点，以区分每个人种/种族组中具有临床显著性和非显著性IR的受试者。4)在临床研究中心的受控环境中，在我们基于人群的样本子集中进行一项初步验证研究，通过使用频繁采样的静脉葡萄糖耐量试验（FSIGT）检测CRP和脂联素对IR的预测价值。这项研究可能会导致早期识别的个人与IR使用简化的实用方法。这将有助于我们制定新的战略，一级预防冠心病，CVA和糖尿病。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.