Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes Mellitus

Recruiting

• Conditions: Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies
• Interventions: Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy; Diagnostic Test: Transthoracic echocardiography; Diagnostic Test: Computed tomography coronary artery calcium scoring; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Manganese-enhanced magnetic resonance imaging (MEMRI); Diagnostic Test: Ambulatory blood pressure monitoring; Diagnostic Test: Accelerometer watch; Diagnostic Test: Blood tests

• Registration Number: NCT03132129
• Lead Sponsor: University of Leicester

Brief Summary

Background: Heart failure is a major cause of morbidity and mortality in diabetes mellitus, but its pathophysiology is poorly understood.

Aim: To determine the prevalence and determinants of subclinical cardiovascular dysfunction in adults with type 2 diabetes (T2D).

Plan: 518 asymptomatic adults (aged 18-75 years) with T2D will undergo comprehensive evaluation of cardiac structure and function using cardiac MRI (CMR) and spectroscopy, echocardiography, CT coronary calcium scoring, exercise tolerance testing and blood sampling. 75 controls will undergo the same evaluation.

Primary hypothesis: myocardial steatosis is an independent predictor of left ventricular global longitudinal strain. Secondary hypotheses: will assess whether CMR is more sensitive to detect early cardiac dysfunction than echocardiography and BNP, and whether cardiac dysfunction is related to peak oxygen consumption.

Expected value of results: This study will reveal the prevalence and determinants of cardiac dysfunction in T2D, and could provide targets for novel therapies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-19
• Study First Submitted QC: 2017-04-24
• Study First Posted: 2017-04-27
• Study Start: 2017-10-24
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-03
• Last Update Posted: 2024-01-05
• Primary Completion: 2029-10-31
• Study Completion: 2029-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 593

Inclusion Criteria

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged ≥18 and ≤75 years.
• Diagnosed with Stable type 2 diabetes (determined by: i) formal diagnosis in GP case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

Exclusion Criteria

• Angina pectoris or limiting dyspnoea (>NYHA II),
• Major atherosclerotic disease: Symptomatic CAD, history of myocardial infarction, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.
• Atrial fibrillation or flutter.
• Moderate or severe valvular heart disease.
• History of heart failure or cardiomyopathy.
• Type 1 diabetes mellitus (T1DM).
• Low fasting C-peptide levels suggestive of adult-onset T1DM.
• Stage III-V renal disease (estimated glomerular filtration rate ≤30ml/min/1.73m2).
• Absolute contraindications to CMR.

Importantly, patients with subclinical CAD, and other common comorbidities such as obesity and hypertension, will not be excluded from this study. This will enable us to evaluate the contribution of CAD to myocardial dysfunction in diabetes and ensures our study group is representative of the general population with diabetes. Similarly, as mild dyspnoea is extremely common and non-specific participants with mild dyspnoea will be included.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Type 2 diabetics	Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Transthoracic echocardiography	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Computed tomography coronary artery calcium scoring	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Blood tests	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Healthy controls	Blood tests	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Transthoracic echocardiography	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Computed tomography coronary artery calcium scoring	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Type 2 diabetics	Accelerometer watch	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Cardiopulmonary exercise testing	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Manganese-enhanced magnetic resonance imaging (MEMRI)	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Type 2 diabetics	Ambulatory blood pressure monitoring	Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.
Healthy controls	Cardiopulmonary exercise testing	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Ambulatory blood pressure monitoring	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Accelerometer watch	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.
Healthy controls	Manganese-enhanced magnetic resonance imaging (MEMRI)	Cases will be compared with age-, gender- and ethnicity-matched healthy controls.

Primary Outcome Measures

Name	Time	Method
Prevalence of early heart failure in type 2 diabetes	5 years	Proportion of participants with type 2 diabetes who have features of early heart failure

Secondary Outcome Measures

Name	Time	Method
Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes	5 years	Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes
Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.	3 years	Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.
Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes	3 years	Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes
Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes	3 years	Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes
Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes	3 years	Independent association of CMR measures (LV systolic and diastolic strain and strain rates) with aerobic exercise capacity (peak VO2) in type 2 diabetes
Differences in LV remodelling (indexed LV mass) between cases and controls	3 years	Differences in LV remodelling (indexed LV mass) between cases and controls
Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls	3 years	Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls
Differences in aerobic exercise capacity (peak V02) between cases and controls	3 years	Differences in aerobic exercise capacity (peak V02) between cases and controls
Differences in myocardial perfusion reserve between cases and controls	3 years	Differences in myocardial perfusion reserve between cases and controls
Differences in heart rate and blood pressure variability between cases and controls	3 years	Differences in heart rate and blood pressure variability between cases and controls
Myocardial steatosis	3 years	Myocardial steatosis as an independent predictor of LV global longitudinal strain
Myocardial calcium handling as assessed by manganese-enhanced magnetic resonance imaging (MEMRI)	5 years	Manganese influx constants calculated using Patlak modelling
Proteomic signature	5 years	Proteomic analysis will be conducted to identify a proteomic signature of early heart failure in type 2 diabetes that will be externally validated
Remission of type 2 diabetes	5 years	The phenotype of participants defined as in remission will be compared to active type 2 diabetes and healthy volunteers

Trial Locations

Locations (1)

University of Leicester; 🇬🇧 Leicester, United Kingdom