Approximately 10 percent of premature coronary artery disease (CAD) morbidity and mortality in the general population is due to insulin dependent diabetes mellitus (IDDM). By age 55, 35 percent of IDDM patents die of CAD, in contrast to only 8 percent of nondiabetic men and 4 percent of women. In the U.S., IDDM affects at least 750,000 persons and this number is growing rapidly as the effect of increasing incidence and improved survival. Tight blood glucose control ran slow the development of microvascular complications but a protective effect on heart disease has not been convincingly demonstrated. This observational population-based study will evaluate cross- sectionally a population-based group of 800 IDDM patients aged 20-49 years and 600 of their non-diabetic spouse/partner controls using the electron-beam computed tomography (EBCT). We will compare the patients and controls in terms of the amount and anatomical distribution of coronary artery calcium (CAC), a marker of atherosclerosis, and the left ventricular (LV) area, a marker of LV hypertrophy and diabetic cardiomyopathy. We will define the demographic, metabolic, and behavioral factors associated with increased CAC and LV area. Using standard epidemiological methods, we will determine the prevalence of clinical CAD, defined by previous MI, revascularization, or angina in the study population. In 100 asymptomatic high-risk IDDM patients (CAC greater than or equal to 20 or LV area greater than 60 cm2), in 50 low-risk patients (CAC and LV area below these cut-offs), and in 20 nondiabetic controls age-sex matched to the high-risk patients, we will perform ECG-gated rest-stress technetium-99m sestamibi single-photon emission computed tomographic imaging (MIBI SPECT). This will help us to determine the presence of myocardial perfusion defects and to quantify myocardial perfusion reserve as well as to relate these findings anatomically to the distribution of CAC by EBCT. In addition, we will determine the LV volumes, ejection fraction, wall motion and thickening, and relate these findings to LV area by EBCT. Finally, the study cohort of 800 IDDM patients and 600 non diabetic spouses/partners will be followed up for a period of 3 years to measure the change in CAC and LV area using a repeat EBCT and to identify the metabolic and behavioral risk factors for progression in these indices. We will also monitor cause-specific mortality and ascertain all fatal and non-fatal cardiac events. In the subgroup of 100 high-risk IDDM patients studied with the MIBI SPECT at the baseline and in all low-risk patients whose CAC increased by more than 50 during the follow-up, we will evaluate using MIBI SPECT the change in myocardial perfusion, LV volumes, ejection fraction, wall motion and thickening, as well as to relate these findings to the change in CAC and LV area by EBCT. This proposed study will better define the causes of increased heart disease risk in IDDM patients, develop appropriate screening methods, and set the stage for effective primary prevention.
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