Coronary Artery Plaque Burden and Morphology in Type 2 Diabetes Mellitus.

Study Overview
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Brief Summary
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Unstable plaque, the primary cause of myocardial infarction, is characterized by distinct a morphology including positive remodeling (PR), low attenuated plaque (LAP), napkin ring sign (NRS), and spotty calcifications (SC) The purpose of the present study is to investigate the influence of microvascular dysfunction and additional risk factors on plaque morphology and plaque burden in patients with diabetes mellitus.

Detailed Description
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Coronary artery disease (CAD) is the leading cause of death and morbidity in type 2 diabetes mellitus (T2DM) and diabetics holds the same risk for death or myocardial infarction (MI) as patients with a prior (MI) without diabetes. In addition to macrovascular complications, and traditional cardiac risk factors, T2DM is burdened by microvascular dysfunction affecting several organs. The dynamics between microvascular dysfunction, known cardiac risk factors and coronary atherosclerosis in diabetic disease is not well characterized. In the present study, a primary cohort of 300 type 2 diabetics and a subgroup of 50-100 type 1 diabetics will be examined with CCTA at baseline and after one year. In addition, CAD in diabetes will be compared to a historical cohort of patients with acute myocardial infarction (AMI). All study participant will undergo the following examinations at baseline: CCTA CAC-score Transthoracic echocardiography 12-lead ECG Blood pressure and pulse frequency Height, weight, waist to hip-ratio Blood samples and urin samples Medical history After 12 months all of the above examinations will be repeated.

Official Title
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Coronary Artery Plaque Burden in Type 2 Diabetes Mellitus. Changes Over Time, Relation to Risk Profile, and Comparison to Acute Myocardial Infarction.

Conditions
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Microalbuminuria, Type2 Diabetes, Atherosclerosis, Plaque, Atherosclerotic, Plaque Vulnerability, Diabetes Complications, Coronary Computed Tomography Angiography

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Type 1 or 2 diabetes mellitus Ability to provide informed conscent Exclusion Criteria: History of CAD Symtoms of CAD (angina) Any tachyarrhythmias making CCTA impossible Glumerular filtration rate (GFR)< 45 ml/min Allergy to iodine contrast Critical illness with life expectancy less than 1 year Documented heart failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 2 diabetes<br>This group will consist of 300 patients with type 2 diabetes mellitus without symptoms or known coronary heart disease. The group will be followed for one year and CCTA will be performed at baseline and after one year. | |
| Type 1 diabetes<br>This group will consist of 50-100 patients with type 1 diabetes mellitus without symptoms or known coronary heart disease. The group will be followed for one year. CCTA will be performed at baseline and after one year. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plaque burden stratified by diabetic complications. | Changes in plaque burden (percentage) during 12 months in diabetics with or without diabetic complications. | Baseline,12 months. | 
| Changes in plaque burden stratified by cardiovascular risk factors | Changes in plaque burden during 12 months stratified by cardiovascular risk factors (hypertension,hypercholersterolemia, smoking, overweight/obesity) | Baseline, 12 months | 
| Changes in plaque morphology stratified by diabetic complications | Changes in plaque morphology (PR, LAP, NRS, SC) during 12 months in diabetics either with or without diabetic complications. | Baseline, 12 months | 
| Changes in plaque morphology stratified by cardiovascular risk factors. | Changes in plaque burden during 12-months stratified by cardiovascular risk factors | Baseline,12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plaque burden in diabetes compared to AMI-patients without diabetes. | A comparison of plaque burden (percentage) in diabetes and a historical cohort of AMI-patients. | Baseline and 12 months | 
| Changes in plaque morphology in diabetes compared to AMI-patients without diabetes. | A comparison of plaque morphology in diabetes and a historical cohort of AMI-patients. | Baseline,12-months | 
| Changes in plaque burden during 12 months in relation to HbA1c and cholesterol levels. | Changes in plaque burden during 12 months stratified by historical levels of cholesterol and HbA1c levels recorded from onset of diabetes to present. | Baseline,12-months | 
| Changes in plaque morphology during 12 months in relation to HbA1c and cholesterol levels. | Changes in plaque morphology during 12 months stratified by historical levels of cholesterol and HbA1c levels recorded once a year from onset of diabetes to present. | Baseline,12-months | 
| Impact of asymtomatic CAD in diabetes on future events. | Long term follow-up to evaluate the impact of asymptomatic CAD (plaque burden and morphology) in diabetes on death, coronary heart attack, hospitalization due to unstable angina, heart failure and ischemic stroke. Clinical outcomes will be recorded from journal records and analyzed after 5-7 years. | 5-7 years |