CMR in T2DM: The NSR Cohort

Cardiac Magnetic Resonance Imaging in Type 2 Diabetes Mellitus: The Næstved/Slagelse/Ringsted Cohort

This study aims to investigate the myocardial phenotype of patients with type 2 diabetes. From 2016-2019 the investigators recruited a cohort of 296 subjects with type 2 diabetes. All subjects underwent clinical examinations including a gadolinium contrast cardiac MRI.

The current study is a clinical follow-up study of the subjects, thus, the investigators will invite all participants to a reevaluation with cardiac MRI.

Additionally, the investigators will aim at recruiting additionally 400 patients with type 2 diabetes.

The aim it to characterize the phenotype of diabetic cardiomyopathy. Uniquely using cardiac MRI we can measure myocardial microvascular function, myocardial localised and diffuse fibrosis in addition to the quantification of myocardial structure and systolic and diastolic function.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Coronary Microvascular Dysfunction; Cardiovascular Magnetic Resonance Imaging; Myocardium; Fibrosis
• Intervention / Treatment: Diagnostic test: All subjects will undergo cardiac magnetic resonance imaging with gadolinium contrast and with adenosine myocardial perfusion

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

Study Locations

• Denmark
  • Slagelse, Denmark, 4200
    • Slagelse Hospital, department of cardiology and endocrinology, medicine 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Unable to give informed consent
• Absolute contraindications to CMR
• Severe claustrophobia
• Type 1 diabetes mellitus
• More than trivial paroxysmal atrial fibrillation, i.e. persistent or permanent atrial fibrillation
• Women of childbearing potential not on acceptable contraception
• Contraindications to adenosine, e.g. 2nd or 3rd degree AV-block, severe hypotension, long QT-syndrome, unstable angina pectoris, sinus node dysfunction, decompensated heart failure

Description

Inclusion Criteria:

Few and simple, allowing for a broad cohort.

• Male or female fully capable of providing informed consent
• Informed consent
• Age 18-80 (both included)
• T2DM diagnosed at least 3 months prior to inclusion in the study

Exclusion Criteria:

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with type 2 diabetes; This group will be split up into different groups. DM2 with vs. without complications to diabetes DM2 with vs. without albuminuria/nephropathy or autonomic neuropathy or retinopathy or peripheral neuropathy or macrovascular angiopathy	Diagnostic test: All subjects will undergo cardiac magnetic resonance imaging with gadolinium contrast and with adenosine myocardial perfusion; This is a observational follow up study accordingly all subjects will undergo the same examinations; Other Names: Echocardiography; medical interview; general medical examination, BP, HR e.g.; Examination for non cardiac complications to diabetes
sex and age matched control subjects	Diagnostic test: All subjects will undergo cardiac magnetic resonance imaging with gadolinium contrast and with adenosine myocardial perfusion; This is a observational follow up study accordingly all subjects will undergo the same examinations; Other Names: Echocardiography; medical interview; general medical examination, BP, HR e.g.; Examination for non cardiac complications to diabetes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of myocardial microvascular function in patients with type 2 diabetes with MACE after 5 years	Myocardial microvascular function is measured by the myocardial perfusion ratio, quantified by cardiac MRI. MACE defined as CVD events (AMI, HF, stable angina, atrial fibrillation, ventricular arytmia), stroke, death	5 years follow-up
Clinical factors associated with worsening of diabetic cardiomyopathy after 5 years	Clinical factors :Albuminuria, autonomic neuropathy, retinopathy, HbA1c, hs-CRP. Signs of worsening af diabetic cardiomyopathy: Increased myocardial extracellular volume, decreased myocardial blood flow and myocardial perfusion reserve, decreased strain (GLS; GCS, GRS), increasing E/e´, increasing concentri remodeling index(LV mass / LV end-diastolic volume)	5 years follow-up
Impact of myocardial perfusion and cardiac cardiac output on perfusion in other organs (kidney, spleen, liver) assed by gadolinium contrast magnetic resonance imaging	Myocardial perfusion measured by myocardial blood flow and myocardial perfusion ratio quantified by cardiac MRI.	Baseline and at 5 years follow-up
The association of pericardial- and epicardial fat with myocardial function and MACE after 5 year	Myocardial function: LVEF, LV strain (GLS, GCS, GRS), E/e´, myocardial extracellular volume, myocardial perfusion ratio. MACE defined as CVD events (AMI, HF, stable angina, atrial fibrillation, ventricular arytmia), stroke, death	Baseline and at 5 years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the progression of diabetic cardiomyopathy over 5 years, including LV+RV function, the coronary microvascular function, the coronary macrovascular function, fibrosis, aortic stiffness, per and epicardial fat, perfusion of other organs	Using multivariable regression including age, sex, smoking, Hypertension, HbA1c, CRP, blood pressure, albuminuria, autonomic neuropathy, retinopathy factors associated with either progression or regression of diabetic cardiomyopathy will be tested. Progression of diabetic cardiomyopathy will be defined as increasing myocardial extracellular volume, decreasing myocardial perfusion reserve, decreasing strain (GLS, GCS, GRS), increasing E/e´compared to baseline.	5 years follow-up

Collaborators and Investigators

• Sponsor: Slagelse Hospital
• Collaborators: Herlev Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: SJ-992

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On request and with the proper approvals
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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