This application is for a field center site to study the interactions between insulin, insulin resistance, hyperglycemia, and cardiovascular disease. RFA NIH-91-HL-03-P. We propose to investigate these relationships in approximately 600 subjects who are a part of a larger prospective study (NIH DK-30747) underway in a bi-ethnic rural community of Hispanics and non-Hispanic whites (NHWs) in two Colorado counties. The two ethnic components of the San Luis Valley Diabetes Study (SLVDS) and both sexes will be represented. At the time of examination, the subjects will be 35-64 years old, one third of the study population is expected to have non-insulin-dependent diabetes mellitus (NIDDM), 20% will have impaired glucose tolerance (IGT) and the remaining persons will have normal glucose tolerance (NGT). A large amount of data will be collected at no cost to the proposed study, because it will be integrated with a routinely scheduled SLVDS follow-up visit. A limited number of measurements would be added to the existing SLVDS protocol, to better assess insulin resistance and cardiovascular disease. By studying a part of the SLVDS cohort, which is independently being followed for cardiovascular morbidity and mortality, it will be possible to determine the prognostic importance of the expected cross-sectional associations between insulin resistance and cardiovascular disease. The main hypothesis is that insulin resistance accelerates atherosclerosis in NHWs but in Hispanics the strength of this effect is inversely related to the degree of Amerindian genetic admixture. Ethnic differences in insulin resistance associations with hypertension, dyslipidemia or impaired fibrinolysis may explain lower cardiovascular morbidity in insulin resistant Hispanics, compared to insulin resistant NHWS. This hypothesis will be tested by meeting the specific aims: 1. To develop a protocol common for collaborating centers, which can be standardized, is safe for subjects, feasible for this epidemiological study, and which allows measurement of insulin resistance, its risk factors and endpoints of clinical and subclinical cardiovascular disease. 2. To measure insulin resistance in a representative sample of individuals with normal, impaired or diabetic glucose tolerance and to relate the observed levels of insulin resistance to the individual and group cardiovascular risk factor profile. 3. To determine the prevalence of clinical and subclinical atherosclerosis, hypertension, left ventricular hypertrophy and cardiovascular autonomic neuropathy over the entire range of insulin resistance and glucose tolerance. 4. To define the effect of factors related to Hispanic and NHW ethnicity (e.g., Amerindian genetic admixture, body fat pattern, socioeconomic status), on the association between insulin resistance and the these cardiovascular endpoints.
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