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.
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