The Insulin Resistance and Atherosclerosis Study (IRAS) is a multicenter study of the relationship between insulin resistance and cardiovascular disease (CVD) and its risk factors in a tri-ethnic (African American, Hispanic, and non-Hispanic white) population aged 40 to 69 years at baseline. The study population was selected to insure adequate numbers of participants within gender and glucose tolerance groups (normal, impaired glucose tolerance, and non-insulin dependent diabetes mellitus [NIDDM]). IRAS is the first large epidemiologic study to include detailed measurements of insulin sensitivity and secretion. During the first four years of funding the IRAS Investigators successfully designed and implemented the first phase of the study -- a cross-sectional evaluation of l,626 participants. The current proposal requests an additional five years of funding for the prospective follow-up and reexamination of the IRAS cohort. The requested funding period consists of three phases. During the first phase, (Y05 and Y06), the investigators propose to conduct a substudy to address the measurement of insulin sensitivity in individuals with NIDDM. This study will evaluate several alternative techniques for measuring insulin sensitivity in approximately 115 non-IRAS volunteers with NIDDM. In addition, all IRAS participants will be contacted annually for incident cardiovascular and other major health events. During the second phase, (Y07 and Y08), a follow-up examination of the IRAS cohort will be conducted with the goal of determining predictors of changes in insulin sensitivity, cardiovascular risk factors, measures of atherosclerosis development, and incident cardiovascular events. Additionally, throughout the first four years (Y05-Y08), there will be a continued major effort devoted to the analysis and reporting of the cross-sectional data from the first IRAS examination. The final phase (Y09) will be devoted to database closure and archival, and analysis and reporting of the longitudinal results.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHL1-CCT-H (S1))
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University of Colorado Denver
Public Health & Prev Medicine
Schools of Medicine
United States
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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
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
Lorenzo, C; Hanley, A J; Rewers, M J et al. (2016) Discriminatory value of alanine aminotransferase for diabetes prediction: the Insulin Resistance Atherosclerosis Study. Diabet Med 33:348-55
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
Wessel, Jennifer; Chu, Audrey Y; Willems, Sara M et al. (2015) Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun 6:5897
Lorenzo, Carlos; Hanley, Anthony J; Rewers, Marian J et al. (2014) Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range. Acta Diabetol 51:617-23
Lorenzo, Carlos; Hanley, Anthony J; Rewers, Marian J et al. (2014) Calcium and phosphate concentrations and future development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diabetologia 57:1366-74
Lorenzo, Carlos; Hanley, Anthony J; Haffner, Steven M (2014) Differential white cell count and incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diabetologia 57:83-92

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