Cardiac Rest and Stress Metabolism in Patients With Type 2 Diabetes (CardioMET)

Cardiac Rest and Stress Metabolism in Patients With Type 2 Diabetes - The CardioMET Study

The number of people with diabetes is rising. One of the major causes of premature death in diabetes is heart failure (HF). This is when the heart cannot pump blood effectively, and this may be related to abnormalities in energy production in the heart muscle. In healthy people, the heart muscle cells show flexibility and can use both sugar and fat molecules for energy production. Although burning fat provides more energy, this process requires more oxygen than burning sugars. As a result, fat is a less efficient fuel for the heart compared to sugars, especially in situations where the energy and oxygen needs are higher, such as during exercise. The investigators propose that the heart muscle in patients with type 2 diabetes relies heavily on fat for energy provision, and fails to burn more sugar molecules for energy provision during exercise to more efficiently use oxygen. Fat and sugar uptake by the heart can be detected by the difference between the blood sugar and fat levels delivered to the heart and returning from the heart, both at rest and also when the heart is working faster during Dobutamine infusion. Dobutamine is a drug frequently used to mimic exercise, and get the heart running faster during medical tests. To test the hypothesis, the investigators will assess fat and sugar uptake by the heart at rest and when the heart is running faster, in patients with type 2 diabetes undergoing investigations to rule out coronary disease. Heart function, and blood supply to heart muscle, at rest and during Dobutamine infusion, will also be measured using MRI scanning. The same tests will be performed in people without diabetes for comparison. It will help understand diabetic heart disease and which aspects may be targeted with new treatments.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Metabolic Disturbance; Fatty Acid Oxidation Disorder; Metabolic Cardiomyopathy
• Intervention / Treatment: Other: Surely observational based on disease state

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • Glenfield Hospital, University Hospitals of Leicester NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Group 1. Patients with T2D and no significant CAD (<50% luminal stenosis on coronary angiography) Group 2. Non-diabetic individuals with no significant CAD (<50% luminal stenosis on coronary angiography)

Description

Inclusion Criteria:

Group 1: Type 2 diabetes cohort:

1. Participant is willing and able to give informed consent for participation in the study.
2. Aged 18 years or above.
3. Confirmed diagnosis of T2D according to World Health Organisation (WHO) criteria
4. Undergoing invasive coronary angiography for exclusion of CAD.
5. Able (in the investigator's opinion) and willing to comply with all study requirements
6. Must understand written and verbal English

Group 2: Non-diabetic Controls

1. Participant is willing and able to give informed consent for participation in the study.
2. Aged 18 years or above.
3. Undergoing invasive coronary angiography for exclusion of CAD.
4. Able (in the investigator's opinion) and willing to comply with all study requirements.

Exclusion Criteria:

Group 1

1. Type 1 diabetes.
2. Significant CAD> (50% luminal stenosis)
3. Significant renal impairment (eGFR<30ml/min/m2).
4. Previous coronary artery bypass grafting surgery or myocardial infarction
5. Significant clinical established diagnosis of heart failure and EF <40%
6. Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
7. Participants who have participated in another research study involving an investigational product in the past 12 weeks
8. Atrial fibrillation.
9. Contra-indications to magnetic resonance imaging (pacemaker, cranial aneurysm clips, metallic ocular foreign bodies, severe claustrophobia).
10. Known hypersensitivity to dobutamine or gadolinium.
11. Participants with a diagnosis of significant (>moderate,) valve disease.

1. Patients who are on Insulin therapy, or oral Thiazolidinedione. 2. Involvement in other studies thought to compromise resulting study data or the health of the participant in the opinion of investigator.

Group 2

1. As per group 1 plus
2. Diagnosis of diabetes or impaired glucose tolerance Note patients with previous CAD treated by angioplasty/stenting and no residual disease are eligible.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 2 Diabetes	Other: Surely observational based on disease state; Metabolism in T2DM vs non diabetic
Non Diabetic	Other: Surely observational based on disease state; Metabolism in T2DM vs non diabetic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in myocardial FA extraction fraction (%) between T2D patients and non-diabetic controls at rest.	Myocardial extraction fraction	Immediate at rest and stress

Collaborators and Investigators

• Sponsor: University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Cardiomyopathies
• Other Study ID Numbers: 0633

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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