Approximately 10% of premature coronary artery, disease (CAD) morbidity and mortality in the general population is due to Type 1 diabetes (T1D). In the U.S., TID affects at least 1.4 million people and this number is growing rapidly as the effect of increasing incidence and improved survival. While tight blood glucose control can slow the development of microvascular complications, optimal approaches to prevention of heart disease in T1D are unknown. This project, called Coronary Artery Calcification in Type 1 Diabetes (CACTI) study began in 2000 (R01 HL61753, Marian Rewers, P.I.). We established a unique cohort of 656 type 1 diabetic patients (age 20-55, minimal diabetes duration of 10 yrs) and their 764 non-diabetic spouses or friends (age 20-55) who are being followed for development of coronary artery disease. Participants have been well characterized during the baseline examination (4/00-3/02) and are undergoing a 3-year follow-up examination (1/03-4/04). To date, partial prospective follow up data have already provided important insights into the modifiable predictors of premature CAD in T1D. We are proposing to follow this cohort for 3 more years to achieve the following specific aims: 1. To determine, among T1D patients and comparable controls, the risk factors for: a. 6-year progression of electron-beam tomography (EBT) defined coronary calcification - marker of coronary atherosclerosis. b. 6-year development of myocardial perfusion defects and changes in relative myocardial perfusion reserve defined using ECG-gated rest-stress technetium-99m MIBI SPECT imaging. c. 6-year incidence of clinical CAD, defined by fatal and non-fatal MI, revascularization or angina, as well stroke, peripheral artery disease and cause-specific mortality. 2. To develop a clinically useful measure of insulin sensitivity that is directly comparable between T1D patients and non-diabetic persons to more precisely determine the role of insulin resistance in development of premature CAC in type I diabetes. This proposed study will better define the causes of increased heart disease risk in T1D patients, develop appropriate screening methods, and set the stage for effective primary prevention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL061753-08
Application #
7110220
Study Section
Special Emphasis Panel (ZRG1-HOP-L (90))
Program Officer
Harman, Jane
Project Start
1999-09-01
Project End
2008-06-30
Budget Start
2006-09-01
Budget End
2007-06-30
Support Year
8
Fiscal Year
2006
Total Cost
$748,596
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Millstein, Richard J; Pyle, Laura L; Bergman, Bryan C et al. (2018) Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI cohort. J Diabetes Complications 32:418-423
Bjornstad, Petter; Pyle, Laura; Cherney, David Z I et al. (2018) Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study. Nephrol Dial Transplant 33:1189-1196
Shah, V N; Sippl, R; Joshee, P et al. (2018) Trabecular bone quality is lower in adults with type 1 diabetes and is negatively associated with insulin resistance. Osteoporos Int 29:733-739
Jensen, Thomas; Bjornstad, Petter; Johnson, Richard J et al. (2018) Copeptin and Estimated Insulin Sensitivity in Adults With and Without Type 1 Diabetes: The CACTI Study. Can J Diabetes :
Bjornstad, Petter; Pyle, Laura; Kinney, Gregory L et al. (2017) Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. J Diabetes Complications 31:369-374
Alman, Amy C; Smith, Steven R; Eckel, Robert H et al. (2017) The ratio of pericardial to subcutaneous adipose tissues is associated with insulin resistance. Obesity (Silver Spring) 25:1284-1291
Bjornstad, P; Costacou, T; Miller, R G et al. (2017) Predictors of early renal function decline in adults with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies. Diabet Med 34:1532-1540
Duca, Lindsey M; Maahs, David M; Schauer, Irene E et al. (2016) Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes. J Clin Endocrinol Metab 101:686-95
Jarvie, Jennifer L; Wang, Hong; Kinney, Gregory L et al. (2016) Lipoprotein-associated phospholipase A2 distribution among lipoproteins differs in type 1 diabetes. J Clin Lipidol 10:577-86
Bjornstad, Petter; Maahs, David M; Jensen, Thomas et al. (2016) Elevated copeptin is associated with atherosclerosis and diabetic kidney disease in adults with type 1 diabetes. J Diabetes Complications 30:1093-6

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