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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL047892-04
Application #
2223978
Study Section
Special Emphasis Panel (SRC (SB))
Project Start
1991-09-30
Project End
1995-09-29
Budget Start
1994-08-01
Budget End
1995-09-29
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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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
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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