Cardiac Function and Microcirculation: Type 2 DIABetes and ECHOcardiographic Changes Over Time (DIABECHO)

Systolic and Diastolic Left Ventricular Function in Patients With Type 2 DIABetes Mellitus: Changes Over Time and Comparison With Cardiac Microcirculation. An ECHOcardiographic Study

The purpose of this study was to investigate the influence of micro- and macrovascular changes on the cardiac function in relation to left ventricular function and coronary arteries during one year in patients with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Left Ventricular Dysfunction

Detailed Description

The most frequent heart disease in patients with Type 2 Diabetes Mellitus (T2DM) is the premature development of coronary atherosclerosis, which often leads to overt ischemic heart disease (IHD). T2DM can lead to both cardiac dysfunction due to IHD or to diabetic cardiomyopathy. Diabetic cardiomyopathy is defined as an impairment of left ventricular (LV) function without overt obstructive coronary vessel disease. Diabetic cardiomyopathy has been associated with microvascular dysfunction, which leads to the inability of the heart to circulate blood effectively. The microvascular atherosclerotic changes are well known in patients with diabetes, such as impaired vision, kidney function and sensibility. The macrovascular atherosclerotic changes such as plaques in the coronary arteries are strongly associated with reduced left ventricular function.

However, the relationship between micro- and macrovascular atherosclerotic changes and the impact on cardiac function is less certain.

Estimation of cardiac function includes: Left Atrial (LA) Strain, LA Strain Rate (SR), LA Emptying Function (LAEF), LV Ejection Fraction (EF), Fractional Shortening (FS), Global Longitudinal Strain (GLS), Circumferential Strain (CS) and Radial Strain (RS), Strain Rate (SR), Peak Systolic Strain, Post Systolic Strain, Early mitral filling velocity (E), late mitral filling velocity (A), E/A ratio, Deceleration Time (DCT) of early mitral filling velocity, medial and lateral mitral velocities using tissue doppler (e' , a' and s'), E/e' ratio, Isovolumetric Relaxation Time (IVRT), Isovolumetric Closing Time (IVCT), Ejection Time (ET), Myocardial Performance Index (MPI) and Myocardial Work Index (MWI).

In this study, participants will be consisting of non-diabetic subjects and patients with diabetes type 1 + 2. All of the participants have no history of myocardial infarction, heart failure and current symptoms of cardiac disease.

The study population will undergo following examinations:

1. 12-lead electrocardiogram (ECG)
2. Urine- and blood samples.
3. Measurements of anthropometric data and vital parameters
4. Recording of medical history
5. 2D transthoracic echocardiography
6. Coronary flow velocity reserve (CFVR) with adenosine infusion.
7. Coronary computed tomography angiography (CCTA).
8. Free fractional reserve computed tomography (FFR-CT)

The examinations will be repeated at follow-up (however non-diabetic subjects will only have 1 CCTA performed at baseline).

The non-invasive FFR-CT will only be performed once in a subgroup of diabetic patients and non-diabetic subjects from November 2016 until May 2017.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Denmark
  • Svendborg, Denmark, 5700
    • Cardiovascular Research Unit, OUH Svendborg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with diabetes type 1+2 and non-diabetic subjects from the DANCAVAS trial (NCT00662480)

Description

Inclusion criteria:

• Ability to give informed consent
• Estimated glomerular filtration rate (eGFR) > 45 ml/min
• NYHA I + II

Exclusion criteria:

• 2° or 3° AV-block at baseline
• Long QT-syndrome at baseline
• Sinus node dysfunction with long sinus arrest at baseline
• Angina pectoris at baseline
• Ejection fraction (EF) < 40% at baseline
• Atrial fibrillation at baseline
• Usage of dipyridamol at baseline
• Aortic stenosis and left ventricle hypertrophia at baseline
• Aortic insufficiency and left ventricle dilatation at baseline
• Medication for asthma within the last 4 years prior to baseline
• Medication for chronic obstructive pulmonary disease (COPD) at baseline
• Allergy to contrast agent at baseline
• Significant stenosis in left main (LM) / left anterior descending (LAD) artery at baseline
• Not feasible to measure or perform coronary flow velocity reserve (CFVR)
• Poor quality of echocardiographic images
• History of pacemaker
• History of myocardial infarction (MI)
• History of heart failure (HF)
• History of coronary artery bypass grafting (CABG)
• History of aortic valve replacement
• History of atrial fibrillation

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
T2; Patients with type 2 diabetes without myocardial infarction, heart failure and symptoms of cardiac disease at inclusion, were invited from the Outpatient Clinic of Endocrinology or The Eye Photo Clinic at Odense University Hospital (OUH) Svendborg. Diagnosis of diabetes was classified by trained endocrinologists according to international standards with relevant biochemistry. Historical data on urine- and blood samples as well as micro- and macrovascular diabetic complications have been registered consecutively in patients followed at the outpatient clinic in the regional Funen Diabetes Database (FDDB). Data on historical invasive procedures due to cardiac disease were registered in Western Denmark Heart Registry (WDHR).
T1; Patients with type 1 diabetes without myocardial infarction, heart failure and symptoms of cardiac disease at inclusion, were invited from the Outpatient Clinic of Endocrinology or The Eye Photo Clinic at OUH Svendborg. Diagnosis of diabetes was classified by trained endocrinologists according to international standards with relevant biochemistry. Historical data on urine- and blood samples as well as micro- and macrovascular diabetic complications have been registered consecutively in patients followed at the outpatient clinic in the regional FDDB. Data on historical invasive procedures due to cardiac disease were registered in WDHR.
Non-diabetic subjects; Non-diabetic subjects without myocardial infarction, heart failure and symptoms of cardiac disease at inclusion, were included from The Danish Cardiovascular Screening trial (DANCAVAS). A randomized controlled trial with the primary aim to evaluate the health benefits and costeffectiveness of using non-contrast full truncus computer tomography (CT) scans (to measure coronary artery calcification (CAC) and identify aortic/iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for cardiovascular disease in men aged 65-74.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Global Longitudinal Strain (GLS) stratified by Coronary Artery Calcium Score (CAC) in patients with diabetes during one year of follow-up	To evaluate the changes in GLS stratified by CAC during one year of follow-up in patients with diabetes compared to non-diabetic subjects	baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in GLS stratified by Coronary Flow Velocity Reserve (CFVR) in patients with diabetes during one year of follow-up	To evaluate the changes in GLS stratified by CFVR during one year of follow-up in patients with diabetes compared to non-diabetic subjects	baseline, 12 months
Correlation between biomarkers and GLS stratified by CFVR	To evaluate the correlation between biomarkers (C-Reactive Protein, Troponin T, NT-proBNP and Uric Acid) and GLS stratified by CFVR in diabetic patients compared to non-diabetic subjects	12 months
Correlation between biomarkers and GLS stratified by CAC	To evaluate the correlation between biomarkers (C-Reactive Protein, Troponin T, NT-proBNP and Uric Acid) and GLS stratified by CAC in diabetic patients compared to non-diabetic subjects	12 months
Changes in LV function stratified by CAC	To evaluate LV systolic and diastolic function stratified by CAC in patients with diabetes compared to non-diabetic subjects.	baseline, 12 months
Changes in LV function stratified by CFVR	To evaluate LV systolic and diastolic function stratified by CFVR in patients with diabetes compared to non-diabetic subjects.	baseline, 12 months
Changes in LV function stratified by micro- and macrovascular diabetic status	To evaluate changes in LV systolic and diastolic function in relation to albuminuria, retinopathy, neuropathy, diabetes duration and CAC.	baseline, 12 months
Correlation between CFVR and Free Fractional Reserve -Computed Tomography (FFR-CT)	To evaluate the correlation between CFVR and FFR-CT in a subgroup consisting of diabetic patients and non-diabetic subjects.	baseline
Correlation between GLS and FFR-CT	To evaluate the correlation between GLS and non-invasive FFR-CT in a subgroup consisting of diabetic patients and non-diabetic subjects.	baseline
Changes in GLS in patients with long-term diabetes and no macrovascular disease	To evaluate the impact of historical varying levels of HbA1c and cholesterols on GLS at baseline in patients with diabetes and no macrovascular disease.	baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between strain values and framerate	To evaluate the changes in strain values dependant of framerate	baseline, 12 months
Relationship between strain values and omitted myocardial segments	To evaluate the changes in strain values dependant of number of myocardial segments omitted	baseline, 12 months
Correlation between dysglycaemia and Left Ventricle Mass (LVM)	To evaluate the impact of dysglycaemia on LVM in non-diabetic subjects compared to diabetic patients.	Baseline
Left Ventricle (LV) and Left Atrial (LA) function stratified by New York Heart Association (NYHA) functional class	To evaluate LV and LA systolic and diastolic function in relation to NYHA classification	baseline
Changes in cardiac systolic and diastolic function stratified by CAC during five years of follow-up in patients with diabetes	To evaluate the changes in cardiac systolic and diastolic function stratified by CAC during five years of follow-up in patients with diabetes compared to non-diabetic subjects.	baseline, 60months
Changes in cardiac systolic and diastolic function stratified by CFVR during five years of follow-up in patients with diabetes	To evaluate the changes in cardiac systolic and diastolic function stratified by CFVR during five years of follow-up in patients with diabetes compared to non-diabetic subjects.	baseline, 60months
Changes in cardiac systolic and diastolic function stratified by plaque morphology during five years of follow-up in patients with diabetes	To evaluate the changes in cardiac systolic and diastolic function stratified by plaque morphology during five years of follow-up in patients with diabetes compared to non-diabetic subjects.	baseline, 60months
LA function stratified by CFVR	To evaluate atrial function stratified by CFVR in patients with diabetes compared to non-diabetic subjects.	baseline
LA function stratified by micro- and macrovascular status	To evaluate atrial function in relation to albuminuria, retinopathy, neuropathy, diabetes duration and CAC.	baseline

Collaborators and Investigators

• Sponsor: Svendborg Hospital
• Investigators: Study Director: Kenneth Egstrup, DMSci, Odense University Hospital (OUH) Svendborg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2016
• Primary Completion (Actual): September 20, 2018
• Study Completion (Actual): September 20, 2018

Study Registration Dates

• First Submitted: October 30, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 6, 2016

Study Record Updates

• Last Update Posted (Actual): October 22, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Type 1 Diabetes; Cardiac dysfunction; Microcirculation; Coronary Computed Tomography Angiography (CCTA); Global Longitudinal Strain (GLS); Coronary Flow Velocity Reserve (CFVR)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: OUHSVB001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO