Although non-insulin-dependent diabetes (NIDDM) is associated with increased risk for atherosclerotic cardiovascular disease (CVD), a major part of the excess risk is not explained by the diabetic state per se. Insulin resistance, an antecedent of NIDDM, has been found to be associated with several CVD risk factors including hypertension, hyperlipidemia, obesity, and hypercoagulability. The principal aim of the proposal is to test the hypothesis that insulin resistance is an independent risk factor and a precursor for CVD in a large multi-ethnic population.
The specific aims are: 1) to determine if insulin resistance is associated with increased prevalence of CVD independent of obesity, glycemia, and insulinemia; 2) to determine the impact of insulin resistance on CVD risk factors including blood pressure, lipids, lipoproteins, and coagulation factors at different stages of glucose tolerance; 3) to investigate the ethnic differences in the relationship between insulin resistance and CVD; and 4) to establish the basis for a prospective study to determine if insulin resistance predicts the development of CVD and its risk factors. The study will be conducted at three different sites to include four different ethnic groups; non-Hispanic whites (Los Angeles and San Antonio), Blacks (Los Angeles), Mexican Americans (San Antonio), and Pima Indians (Phoenix). Four hundred men and women aged 40-69 years of each ethnic group will be included. They will be selected to cover the three categories of glucose tolerance (normal, impaired, and NIDDM). The following tests and procedures will be performed on each subject over two days. The first day will involve history taking (personal, family, general, medical, dietary, physical activity, and Rose questionnaire), physical examination, and non-invasive cardiovascular evaluation (electrocardiogram, Doppler of peripheral vessels. Duplex scanning of the carotids, and echocardiogram). Blood will be collected for measurement of fasting lipids, lipoproteins, coagulation factors, and glycated hemoglobin, and study of blood rheology (blood and plasma viscosity, and red blood cell aggregation) and an oral glucose tolerance test will be performed. The second day will be devoted to assessment of insulin resistance. The minimal model approach will be used as it is most suited to a large epidemiological study. In addition to being accurate and reproducible, it is easy to perform, safe, and cost-effective. In a subset of subjects, a third visit will be required to study insulin secretion and postprandial lipids and lipoprotein profile after a standardized meal test. The findings of this study are expected to determine the extent and the significance of the relation between insulin resistance and CVD at different stages of glucose tolerance among various ethnic groups which will have public health implications in planning future intervention strategies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL047902-03
Application #
3553516
Study Section
Special Emphasis Panel (SRC (SB))
Project Start
1991-09-30
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Santaren, Ingrid D; Watkins, Steven M; Liese, Angela D et al. (2017) Individual serum saturated fatty acids and markers of chronic subclinical inflammation: the Insulin Resistance Atherosclerosis Study. J Lipid Res 58:2171-2179
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Lorenzo, Carlos; Festa, Andreas; Hanley, Anthony J et al. (2017) Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion. Diabetes Care 40:375-382
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Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Lee, C Christine; Watkins, Steve M; Lorenzo, Carlos et al. (2016) Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 39:582-8
Dickson, J C; Liese, A D; Lorenzo, C et al. (2015) Associations of coffee consumption with markers of liver injury in the insulin resistance atherosclerosis study. BMC Gastroenterol 15:88
Lorenzo, Carlos; Hanley, Anthony J; Rewers, Marian J et al. (2015) Lipoprotein heterogeneity may help to detect individuals with insulin resistance. Diabetologia 58:2765-73

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