Screening For Asymptomatic Obstructive Coronary Artery Disease Among High-Risk Diabetic Patients Using CT Angiography, Following Core 64

Management of Patients Randomized to the Control Arm: Subjects randomized to the control arm
will continue to be followed by their primary care physicians with the recommendation that
they follow standard guidelines for management of diabetic patients.

Management of Patients Randomized to the Asymptomatic Screening Arm: Subjects randomized to
the Asymptomatic Screening arm will undergo initial CT screening in the following fashion:

- Subjects with serum creatinine of < 2.0 mg/dl (men) or <1.8 mg/dL (women) will be
screened using multi-slice CT angiography with contrast.

- Those with serum creatinine ≥ 2.0 mg/dl (men) or >1.8 mg/dL (women) will be screened
without contrast to obtain a coronary calcium score. Further cardiac screening will be
determined based on these results.

Subjects Receiving Multi-Slice CT Angiography (serum creatinine of < 2.0 mg/dl (men) or <1.8
mg/dL (women)): Subjects severe stenosis will proceed to coronary angiography and
revascularization as needed. Subjects with moderate stenosis will be referred for adenosine
stress cardiac MRI. If ischemia is detected, they will also be referred for coronary
angiography. Subjects with either mild stenosis or normal coronary arteries will receive no
further imaging studies.

Subjects Undergoing CT Evaluation for Coronary Calcium Scoring (serum creatinine ≥ 2.0 mg/dl
(men) or >1.8 mg/dL (women): Subjects with coronary calcium scores >100 or >75th percentile
will be referred for adenosine stress cardiac MRI. If ischemia is detected, they will be
referred for coronary angiography. Subjects with coronary calcium scores = 0-10 or 11-100
and <75th percentile will receive no further imaging studies.

Medical Management (Only for those patients randomized to the Asymptomatic Screening Arm):
In addition to the imaging studies and potential coronary revascularization procedures
performed as described above, all subjects will be placed on one of two medical regimens:

- Standard Appropriate DM Care and

- Aggressive Risk Factor Reduction Care.

Standard Appropriate DM Care: Subjects assigned to this form of medical care will be managed
by their primary physicians. This type of care will consist of targeting the goals proposed
by Intermountain Healthcare for all patients with diabetes. These include the following
three targets: HgA1C <7.0%, LDL cholesterol <100 mg/dL and Systolic BP<130 mm Hg. Subjects
assigned to Standard Care will include all control subjects, as well as all screened
subjects with either a normal CT angiogram or a coronary calcium score = 0-10.

Aggressive Risk Factor Reduction Care: Subjects assigned to this form of medical care, in
addition to standard medical care provided by their primary physicians, will also be managed
by their primary physicians, but will receive more aggressive risk factor reduction
management according to a set of guidelines that will be given to the primary physicians.
This aggressive management strategy, designed to address the increased medical risk among
the asymptomatic diabetics with detected vascular disease, will consist of more aggressive
glucose and lipid targets than is in the Standard Care protocols and specific medication
algorithms designed to accomplish these more aggressive targets.

Follow-Up After enrollment into the protocol, all subjects will be followed for two years.
Follow-up will occur by telephone at six-month intervals. Outcomes will be ascertained by
directly questioning the patient and by review of medical records. All primary outcomes
will be adjudicated by an independent events committee. At 24 months, the SF-12
questionnaire will be mailed to all the participants to determine their physical and mental
status.

Inclusion Criteria:

1. Age: Males ≥ 50 years; Females ≥55 years with: History of diabetes mellitus (prior
documentation of fasting glucose ≥ 126 mg/dl or hemoglobin A1C > 6.5%), either type 1
or type 2, documented for at least 3 years and on medication for at least one year.

2. Age: Males ≥ 40 years; Females ≥45 years with: History of diabetes mellitus (prior
documentation of fasting glucose ≥ 126 mg/dl or hemoglobin A1C > 6.5%), either type 1
or type 2, documented for at least 5 years and on medication for at least one year.

3. The patient or legally authorized representative must sign a written informed
consent, prior to the procedure, using a form that is approved by the local
Institutional Review Board.

Exclusion Criteria:

1. Known coronary artery disease (stenosis >70%, history of myocardial infarction, or
angina)

2. Symptomatic cerebral vascular disease (history of TIA, CVA, or cerebrovascular
[carotid or cerebral arteries] revascularization)

3. Symptomatic peripheral vascular disease (history of claudication, amputation, or
peripheral [including renal arteries] arterial revascularization)

4. Treatment with any other investigational drug within the previous 30 days

5. Any therapy or condition that would pose a risk to the patient or make it difficult
to comply with study requirements.

6. Pregnant and/or lactating women, and women of child bearing potential not using
acceptable means of contraception. Women of childbearing potential must be using
adequate measures of contraception (as determined by the Investigator) to avoid
pregnancy and should be highly unlikely to conceive during the study period. Women of
childbearing potential must have a negative pregnancy test at screen.

7. Any life threatening condition/significant co-morbidity such that primary screening
is inappropriate.

-