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

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes; Diabetic Cardiomyopathies
• Intervention / Treatment: Other: high-intensity interval exercise training (HIIT); Other: moderate-intensity exercise training (MIT)

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy controls
Active Comparator: training group 1: HIIT; high-intensity interval exercise training group (T2DM patients)	Other: high-intensity interval exercise training (HIIT); 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).
Active Comparator: training group 2: MIT; moderate-intensity exercise training group (T2DM patients)	Other: moderate-intensity exercise training (MIT); 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.
No Intervention: Detraining period; Follow-up: detraining of group 1 and 2 (T2DM patients)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Jessa Hospital

Publications and helpful links

General Publications

• Van Ryckeghem L, Keytsman C, De Brandt J, Verboven K, Verbaanderd E, Marinus N, Franssen WMA, Frederix I, Bakelants E, Petit T, Jogani S, Stroobants S, Dendale P, Bito V, Verwerft J, Hansen D. Impact of continuous vs. interval training on oxygen extraction and cardiac function during exercise in type 2 diabetes mellitus. Eur J Appl Physiol. 2022 Apr;122(4):875-887. doi: 10.1007/s00421-022-04884-9. Epub 2022 Jan 17.
• Van Ryckeghem L, Keytsman C, Verboven K, Verbaanderd E, Frederix I, Bakelants E, Petit T, Jogani S, Stroobants S, Dendale P, Bito V, Verwerft J, Hansen D. Exercise capacity is related to attenuated responses in oxygen extraction and left ventricular longitudinal strain in asymptomatic type 2 diabetes patients. Eur J Prev Cardiol. 2022 Jan 11;28(16):1756-1766. doi: 10.1093/eurjpc/zwaa007.
• Van Ryckeghem L, Keytsman C, Verbaanderd E, Frederix I, Bakelants E, Petit T, Jogani S, Stroobants S, Dendale P, Bito V, Verwerft J, Hansen D. Asymptomatic type 2 diabetes mellitus display a reduced myocardial deformation but adequate response during exercise. Eur J Appl Physiol. 2021 Mar;121(3):929-940. doi: 10.1007/s00421-020-04557-5. Epub 2021 Jan 8.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Exercise training; Cardiac function; Exercise echocardiography; Diabetic cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Cardiomyopathies; Diabetic Cardiomyopathies
• Other Study ID Numbers: HITDCM01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No