The purpose of the study is to identify a sub-group of diabetic patients at higher risk of progression of coronary disease and also more likely to suffer from heart attack/angina and heart failure. The total number of patients to be recruited in this study will be 250 with type-2 diabetes but no known heart disease. These patients will have an objective measure of the function of the lining of the arteries, CT scan of the arteries of the heart and an ultrasound scan of the heart and arteries of the neck done at baseline along with blood tests for identification new markers of malfunction of the lining and inflammation of the arteries. Patients will be followed up at 18 months. During the follow-up visit, in addition to the blood tests, the CT scan of the heart arteries and ultrasound of the heart and arteries of the neck will be repeated to assess progression of the non-calcified, calcified and mixed plaques in the coronary arteries.

Hypothesis: We hypothesise that a combination of CT coronary angiography, ultrasound of the heart and of the arteries of the neck, evaluation of expression of genetic markers and bio-markers in the blood will help identify diabetic patients at highest risk of heart disease progression,that can result in angina, heart attacks, heart failure and cardiovascular deaths.

Previous studies using coronary calcium scanning in diabetic patients showed that those with the greatest progression in calcified plaque in the coronary arteries were at the highest risk for heart attacks. However, coronary calcium scans only identify the calcified plaque and are not able to pick up non-calcified, cholesterol rich plaques. Cholesterol rich non-calcified plaques are more often associated witn acute heart attacks. CT coronary angiography can identify both calcified and non-calcified plaques and can therefore add significantly to our predictive ability. Certain chemical substances (biomarkers) measured in blood indicate the severity of plaque burden and inflammation in the coronary arteries. A combination of CT coronary angiography, expression of genetic markers, measure of function of the cells lining the blood vessels and biomarkers can help to identify diabetic patients at highest risk of heart attacks, allowing us to start appropriate risk reduction treatments in those patients. In previous studies with coronary artery calcium, patients suffering from heart attacks were those who also had a higher progression of coronary artery calcium (CAC) score. In diabetics, in particular, patients with poor control of their blood glucose also had greater progression of the CAC score. In order to test the validity of our hypothesis, we have decided to base our study on a population of established diabetics with difficult to control blood pressure, high cholesterol and chronic complications of the small blood vessels, i.e. involvement of the retina (back of the eye) and peripheral nerves as well as protein in the urine. Patients with chronic complications of diabetes are known to have higher incidence of heart disease as well.

Methodology and Timetable: Patients will be recruited from Diabetes clinics of NHS hospitals in North West London.

If eligible for the trial, an informed consent will be obtained from the patients and their general practitioner will be subsequently informed about their participation in the trial. Once recruited into the trial, a CT coronary angiogram (CTCA, CT of the arteries of the heart), ultrasound scan of the heart and carotid arteries of the neck as well as a measure of endothelial function will be performed at the Wellington Hospital in St. Johns Wood, London within 1-2 weeks. At the same time, blood samples will also be obtained for bio-markers. A report of the CTCA will then be forwarded to the consultant in-charge of the patient's care as well as to the GP.

If a narrowing of moderate degree (70%) is noted on the CT angiogram, the patient will then be brought back to the Wellington Hospital within 2 weeks for a heart perfusion scan which evaluates the relative discrepancies in flow of blood to the heart muscle and helps plan further management.

If there is significant reduction in blood flow noted in the perfusion scan,patients will be referred back to the consultants for further clinical management.

During their first visit to the Wellington Hospital for the CT scan, blood samples will be taken and stored on-site for biomarker analysis.

Patients will be followed up after 18 months from the time of recruitment into the trial,when a second CTCA, ultrasound of the arteries of the neck will be performed to assess the degree of progression of calcium and cholesterol deposits within the coronary arteries and thickness of the lining of the arteries in the neck in addition to blood sample collection for bio-markers.

Patients with significant narrowing of coronary arteries (>70%) requiring a stent to be inserted in the first scan will be excluded from follow up. Patients with normal coronary arteries on the initial scan also will be excluded from the follow-up.

Inclusion Criteria:

• Established T2DM with or without micro-vascular complications of diabetes (retinopathy, peripheral neuropathy and/or micro-albuminuria)

No history of coronary artery disease (CAD)

Exclusion Criteria:

• 1. Estimated GFR <45 2. Pregnant women 3. Age < 35 years 4. Atrial fibrillation 5. Known allergy to iodine contrast 6. CAC score >1000 Agatston Units

Patients with type 2 diabetes recruited from hospital clinics and one community faith based cardiovascular disease prevention clinic run under the aegis of a lipidologist