Clinical trial NCT03132129: Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes Mellitus
Official title: Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Mellitus, Type 2
Diabetic Cardiomyopathies
Keywords: Type 2 diabetes
Diabetic cardiomyopathy
Cardiovascular magnetic resonance
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 593
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases will be adults with stable type 2 diabetes and no past medical history of known cardiovascular disease.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Prevalence of early heart failure in type 2 diabetes
timeFrame: 5 years
Secondary outcomes:
measure: Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes
timeFrame: 3 years
measure: Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes
timeFrame: 3 years
measure: Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes
timeFrame: 3 years
measure: Differences in LV remodelling (indexed LV mass) between cases and controls
timeFrame: 3 years
measure: Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes
timeFrame: 5 years
measure: Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.
timeFrame: 3 years
measure: Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls
timeFrame: 3 years
measure: Differences in aerobic exercise capacity (peak V02) between cases and controls
timeFrame: 3 years
measure: Differences in myocardial perfusion reserve between cases and controls
timeFrame: 3 years
measure: Differences in heart rate and blood pressure variability between cases and controls
timeFrame: 3 years
measure: Myocardial steatosis
timeFrame: 3 years
measure: Myocardial calcium handling as assessed by manganese-enhanced magnetic resonance imaging (MEMRI)
timeFrame: 5 years
measure: Proteomic signature
timeFrame: 5 years
measure: Remission of type 2 diabetes
timeFrame: 5 years
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University of Leicester
Study officials:
affiliation: University of Leicester
name: Gerry P McCann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yeo JL, Gulsin GS, Brady EM, Dattani A, Bilak JM, Marsh AM, Sian M, Athithan L, Parke KS, Wormleighton J, Graham-Brown MPM, Singh A, Arnold JR, Lawson C, Davies MJ, Xue H, Kellman P, McCann GP. Association of ambulatory blood pressure with coronary microvascular and cardiac dysfunction in asymptomatic type 2 diabetes. Cardiovasc Diabetol. 2022 May 28;21(1):85. doi: 10.1186/s12933-022-01528-2.