Effect of High-intensity Interval Training on Cardiac Function and Regulation of Glycemic Control in Diabetic Cardiomyopathy

Study Overview
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Brief Summary
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According to data of the International Diabetes Federation (IDF), diabetes in general affects approximately 415 million people worldwide and this number is still increasing. Cardiovascular diseases, one of the major complications of diabetes, are the leading cause of mortality and morbidity in the diabetic population. One of the cardiovascular complications is diabetic cardiomyopathy, in which structural and functional changes occur in the heart impairing cardiac function. Exercise training has already proven the benefits on glycemic control in diabetes. This is also the case for the effects on cardiac function. However, as results are conflicting, it remains unclear which elements of exercise training should be focused on. For instance, high-intensity interval training (HIIT) is gaining interest as positive effects are already shown on glycemic control. Therefore, the potential of HIIT to improve cardiac function in diabetes should be investigated. Further on, the effects of exercise training on cardiac function are mainly investigated during rest by the use of transthoracic echocardiography. Therefore, as data are lacking, it remains unclear how the diabetic heart functions during exercise. The aim of the present study is to investigate the effects of different training modalities (e.g. HIIT) on heart function in diabetes both during rest and during exercise itself. Therefore, cardiac function will be evaluated by the use transthoracic (exercise) echocardiography. This will be combined by the evaluation of several biochemical parameters. The results will provide more insight in the pathology of diabetic cardiomyopathy as well as the potential of exercise training for this cardiovascular complication. Eventually, this research will contribute to the optimization of exercise programs for patients with diabetes.

Official Title
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Effect of High-intensity Interval Training on Cardiac Function and Regulation of Glycemic Control in Diabetic Cardiomyopathy

Conditions
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Diabetic Cardiomyopathies, Type2 Diabetes

Intervention / Treatment
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* Other: high-intensity interval exercise training (HIIT)
* Other: moderate-intensity exercise training (MIT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes patients: BMI > 20kg/m² diagnosis of T2DM as stated in guidelines of ADA (American Diabetes Association) stable medication for at least 3 months Healthy controls: BMI > 20kg/m² no diabetes Exclusion Criteria: iron deficiency anemia participation in another clinical trial heart diseases: CAD (coronary artery disease), ischemia, valvular diseases, congenital heart diseases neurological, pneumological, oncological, orthopedic disorders diabetes complications: renal diseases, retinopathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 81 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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: training group 1: HIIT<br>high-intensity interval exercise training group (T2DM patients) | Other: high-intensity interval exercise training (HIIT)<br>* This program includes 24 weeks of exercise training and is divided in different phases (phase 1: week 1-2, equal to the MIT group, phase 2: week 3-6, 6 bouts of high-intensity exercise, phase 3: week 7-12, 7 bouts of high-intensity exercise, phase 4: week 13-24, 8 bouts of high-intensity exercise). The exercise training program consists of 3 exercise sessions per week (for 6 months).<br>|
| Active Comparator: training group 2: MIT<br>moderate-intensity exercise training group (T2DM patients) | Other: moderate-intensity exercise training (MIT)<br>* This program includes 24 weeks of exercise training and is not devided in phases. The exercise training program consists of 3 endurance exercise sessions per week (for 6 months). The total exercise volume equals the exercise volume of the HIIT group.<br>|
| No Intervention: Detraining period<br>Follow-up: detraining of group 1 and 2 (T2DM patients) | |
| No Intervention: Healthy controls<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transthoracic echocardiography (TTE) during excercise | heart function during exercise by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | day 1 | 
| Transthoracic echocardiography (TTE) during excercise | heart function during exercise by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 3 | 
| Transthoracic echocardiography (TTE) during excercise | heart function during exercise by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 6 | 
| Transthoracic echocardiography (TTE) during excercise | heart function during exercise by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 12 | 
| Transthoracic echocardiography (TTE) | heart function in rest by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | day 1 | 
| Transthoracic echocardiography (TTE) | heart function in rest by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 3 | 
| Transthoracic echocardiography (TTE) | heart function in rest by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 6 | 
| Transthoracic echocardiography (TTE) | heart function in rest by means of standard echocardiography: evaluation of diastolic and systolic function (mitral inflow pattern, ejection fraction, tissue doppler imaging, strain rate analyses,…) and cardiac structure (left ventricle mass, intraventricular wall mass,…) | month 12 | 
| ECG (Electrocardiogram) during excercise | ECG during excercise (an incremental exercise test on a cycle) | month 3 | 
| ECG (Electrocardiogram) during excercise | ECG during excercise (an incremental exercise test on a cycle) | month 12 | 
| ECG (Electrocardiogram) | ECG in rest | month 3 | 
| ECG (Electrocardiogram) | ECG in rest | month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic control | glycemic concentrations, HbA1c levels, insulin sensitivity, inflammation, cardiac biomarkers | day 1 | 
| Glycemic control | glycemic control, insulin sensitivity, inflammation, cardiac biomarkers | month 3 | 
| Glycemic control | glycemic concentrations, HbA1c levels, insulin sensitivity, inflammation, cardiac biomarkers | month 6 | 
| Glycemic control | glycemic concentrations, HbA1c levels, insulin sensitivity, inflammation, cardiac biomarkers | month 12 | 
| Insulin metabolism | Fasting serum insulin, homeostasis model assessment insulin resistance and measures of central insulin sensitivity derived from an oral glucose tolerance test (75g) | day 1 | 
| Insulin metabolism | Fasting serum insulin, homeostasis model assessment insulin resistance and measures of central insulin sensitivity derived from an oral glucose tolerance test (75g) | month 3 | 
| Insulin metabolism | Fasting serum insulin, homeostasis model assessment insulin resistance and measures of central insulin sensitivity derived from an oral glucose tolerance test (75g) | month 6 | 
| Insulin metabolism | Fasting serum insulin, homeostasis model assessment insulin resistance and measures of central insulin sensitivity derived from an oral glucose tolerance test (75g) | month 12 | 
| Cardiac function | Cardiac biomarkers (brain-derived natriuretic peptide (BNP) levels, cardiac troponin levels) | day 1 | 
| Cardiac function | Cardiac biomarkers (BNP levels, cardiac troponin levels) | month 3 | 
| Cardiac function | Cardiac biomarkers (BNP levels, cardiac troponin levels) | month 6 | 
| Cardiac function | Cardiac biomarkers (BNP levels, cardiac troponin levels) | month 12 | 
| Inflammation and oxidative stress | C reactive protein (CRP) levels, tumor necrosis factor-(TNF)alpha levels, interleukin (IL)-10 (interleukin) levels, oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX)) | day 1 | 
| Inflammation and oxidative stress | CRP levels, TNF-alpha levels, IL-10 levels, oxidative stress markers (SOD, MDA, GPX) | month 3 | 
| Inflammation and oxidative stress | CRP levels, TNF-alpha levels, IL-10 levels, oxidative stress markers (SOD, MDA , GPX) | month 6 | 
| Inflammation and oxidative stress | CRP levels, TNF-alpha levels, IL-10 levels, oxidative stress markers (SOD, MDA, GPX) | month 12 | 
| body composition | body composition, measured using dual x-ray absorptiometry | day 1 | 
| body composition | body composition, measured using dual x-ray absorptiometry | month 6 | 
| Maximal oxygen uptake (ml/O2/kg/min) | exercise capacity measured using indirect calorimetry and an incremental bicycle exercise protocol | day 1 | 
| Maximal oxygen uptake (ml/O2/kg/min) | exercise capacity measured using indirect calorimetry and an incremental bicycle exercise protocol | month 3 | 
| Maximal oxygen uptake (ml/O2/kg/min) | exercise capacity measured using indirect calorimetry and an incremental bicycle exercise protocol | month 6 | 
| Maximal oxygen uptake (ml/O2/kg/min) | exercise capacity measured using indirect calorimetry and an incremental bicycle exercise protocol | month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise training, Type 2 diabetes, Diabetic cardiomyopathy, Cardiac function, Exercise echocardiography