CRP AND ADIPONECTIN AS MARKERS FOR INSULIN RESISTANCE

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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), dyslipidemia, 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 a 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.