Screening For Asymptomatic Obstructive Coronary Artery Disease Among High-Risk Diabetic Patients Using CT Angiography, Following Core 64
Screening For Asymptomatic Obstructive Coronary Artery Disease Among High-Risk Diabetic Patients Using CT Angiography, Following Core 64
Patients with a known history of diabetes mellitus and no prior documented evidence of
 cardiovascular disease will be evaluated for inclusion in the study. Once qualified, patients
 will be enrolled and be randomized to either the Control Arm or to the Asymptomatic Screening
 Arm. Patients in the Control Arm will be followed by their primary care physicians with the
 recommendation that they follow standard guidelines for management of diabetic patients.

 Patients in the Asymptomatic Screening Arm will undergo CT screening for either coronary
 calcium scoring or multi-slice CT angiography as well as be placed on one of two medical
 regimens. Patients will be followed by telephone at six-month intervals for a minimum of one
 year for both primary and secondary outcomes.
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 a minimum of
 one year. 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.

 Statistical Analysis Both an intention-to-treat analysis and a by protocol analysis will be
 performed. The intention-to-treat analysis will be the primary analysis and will be defined
 as all those randomized to scan versus all those randomized to control regardless of what
 actually happened. The by protocol analysis will be defined as all of those who actually got
 the protocol scan versus those who did not get the scan. Those who did not get the scan
 includes all those randomized to the control arm. If they went outside of the study and got a
 scan anyway, this will be considered to be for clinical indications and will still be in the
 non-protocol scan group. For those who were randomized to get the scan but never did,
 evaluation of their baseline characteristics will be made and if they did not differ from
 those who actually got the scan or from those who were randomized to control, then they will
 be included the didn't get scanned group.
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.

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