NCT03132129

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

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 593 (estimated)
• Sponsor: University of Leicester · Academic / Other
• Sex: All
• Age: 50 Years – 75 Years
• Healthy volunteers: Accepted

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.

Conditions

• Diabetes Mellitus, Type 2
• Diabetic Cardiomyopathies

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy	CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue.
DIAGNOSTIC_TEST	Transthoracic echocardiography	Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function.
DIAGNOSTIC_TEST	Computed tomography coronary artery calcium scoring	Computed Tomography coronary calcium scoring to assess the presence of subclinical atherosclerosis and allow an estimate of atheroma burden in addition to epicardial adipose tissue characterisation and systolic strain.
DIAGNOSTIC_TEST	Cardiopulmonary exercise testing	Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.
DIAGNOSTIC_TEST	Manganese-enhanced magnetic resonance imaging (MEMRI)	A subset of the participants will have cardiac MRI scanning with manganese-based contrast agent, lasting approximately 45-50 minutes. After localisers, baseline functions and native T1 maps have been acquired, Mangafodipir (0.1mL/kg) will be administered intravenously at 1ml/min, with additional T1 maps acquired every 2.5 min after administration of the contrast agent for up to 30 minutes.
DIAGNOSTIC_TEST	Ambulatory blood pressure monitoring	A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.
DIAGNOSTIC_TEST	Accelerometer watch	Watch worn to collect free living physical activity data for 7 days.
DIAGNOSTIC_TEST	Blood tests	Collection of blood samples from each participant to characterise the participant's health status and to develop a proteomic signature of early heart failure.

Timeline

• Start date: 2017-10-24
• Primary completion: 2029-10-31
• Completion: 2029-10-31
• First posted: 2017-04-27
• Last updated: 2024-01-05

Locations

1 site across 1 country: United Kingdom