Overview

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.

Eligibility

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.