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NCT Number: NCT03132129

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

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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Cardiomyopathies Cardiovascular Diseases Diabetes Complications Diabetes Mellitus Diabetic Cardiomyopathies Endocrine System Diseases Glucose Metabolism Disorders Heart Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

50 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Leicester

Leicester, United Kingdom

Location status: Recruiting

Location contact

Gaurav S Gulsin, MRCP(UK)

CONTACT

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Diagnostic Test

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.

Transthoracic echocardiography

Diagnostic Test

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.

Computed tomography coronary artery calcium scoring

Diagnostic Test

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.

Cardiopulmonary exercise testing

Diagnostic Test

Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.

Manganese-enhanced magnetic resonance imaging (MEMRI)

Diagnostic Test

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.

Ambulatory blood pressure monitoring

Diagnostic Test

A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.

Accelerometer watch

Diagnostic Test

Watch worn to collect free living physical activity data for 7 days.

Blood tests

Diagnostic Test

Collection of blood samples from each participant to characterise the participant's health status and to develop a proteomic signature of early heart failure.

Primary outcomes

  1. Prevalence of early heart failure in type 2 diabetes

    Time frame: 5 years

    Proportion of participants with type 2 diabetes who have features of early heart failure

Secondary outcomes

  1. Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes

    Time frame: 3 years

    Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes

  2. Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes

    Time frame: 3 years

    Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes

  3. Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes

    Time frame: 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

  4. Differences in LV remodelling (indexed LV mass) between cases and controls

    Time frame: 3 years

    Differences in LV remodelling (indexed LV mass) between cases and controls

  5. Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes

    Time frame: 5 years

    Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes

  6. Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.

    Time frame: 3 years

    Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.

  7. Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls

    Time frame: 3 years

    Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls

  8. Differences in aerobic exercise capacity (peak V02) between cases and controls

    Time frame: 3 years

    Differences in aerobic exercise capacity (peak V02) between cases and controls

  9. Differences in myocardial perfusion reserve between cases and controls

    Time frame: 3 years

    Differences in myocardial perfusion reserve between cases and controls

  10. Differences in heart rate and blood pressure variability between cases and controls

    Time frame: 3 years

    Differences in heart rate and blood pressure variability between cases and controls

  11. Myocardial steatosis

    Time frame: 3 years

    Myocardial steatosis as an independent predictor of LV global longitudinal strain

  12. Myocardial calcium handling as assessed by manganese-enhanced magnetic resonance imaging (MEMRI)

    Time frame: 5 years

    Manganese influx constants calculated using Patlak modelling

  13. Proteomic signature

    Time frame: 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

  14. Remission of type 2 diabetes

    Time frame: 5 years

    The phenotype of participants defined as in remission will be compared to active type 2 diabetes and healthy volunteers

Study contacts

Contact information is provided by the study sponsor or research team.

Gaurav S Gulsin, MBChB(Hons)

CONTACT

[email protected]

01162583244

Gerry P McCann, MD

CONTACT

[email protected]

01162583402

Sponsors and collaborators

Lead sponsor

University of Leicester

Other

Registry information

Acronym: PREDICT

Important dates

Study start
2017
Primary completion
2029
Study completion
2029
First posted
Apr 27, 2017
Registry last updated
Jan 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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