Multi-modal characterisation of early-stage, subclinical cardiac deterioration in patients with type 2 diabetes

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease.

Methods: We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates.

Results: Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p < 0.001), longer QTc interval (424 vs. 420ms, p < 0.001), reduced T wave amplitude (0.33 vs. 0.37mV, p < 0.001), lower stroke volume (72 vs. 78ml, p < 0.001) and thicker left ventricular wall (6.1 vs. 5.9mm, p < 0.001) despite a decreased Sokolow-Lyon index (19.1 vs. 20.2mm, p < 0.001). T2DM was independently associated with higher heart rate (beta = 3.11, 95% CI = [2.11,4.10], p < 0.001), lower stroke volume (beta = -4.11, 95% CI = [-6.03, -2.19], p < 0.001) and higher left ventricular wall thickness (beta = 0.133, 95% CI = [0.081,0.186], p < 0.001). Trends were consistent in subgroups of different sex, age and body mass index. Fewer significant differences were observed in participants of non-white ethnic background. QRS duration and Sokolow-Lyon index showed a positive association with the development of cardiovascular disease in cohorts with and without T2DM, respectively. A higher left ventricular mass and wall thickness were associated with cardiovascular outcomes in both groups.

Conclusion: T2DM prior to cardiovascular disease was linked with a higher heart rate, QTc prolongation, T wave amplitude reduction, as well as lower stroke volume and increased left ventricular wall thickness. Increased QRS duration and left ventricular wall thickness and mass were most strongly associated with future cardiovascular disease. Although subclinical, these changes may indicate the presence of autonomic dysfunction and diabetic cardiomyopathy.

Keywords: Cardiovascular diseases; Cross-sectional studies; Diabetes mellitus (type 2); Electrocardiography; Magnetic resonance imaging; UK Biobank.

Fig. 1

Cohort selection flowchart. CMR: cardiac magnetic resonance imaging, BMI: body mass index, CVD: cardiovascular disease, T2D: type 2 diabetes. Baseline refers to the time of recording of the ECG and CMR images. Follow-up refers to the period between baseline and censoring date (21/09/2021)

Fig. 2

Incident cardiovascular disease (CVD) diagnoses in the control and type 2 diabetes cohorts during the follow-up period after the imaging and ECG assessment. Total count for each CVD category is indicated at the top of each bar. The shaded areas represent cases where this CVD exists in conjunction with one or more other CVD diagnoses. Each cohort includes n = 98 individuals with one or more CVD(s) developed during the follow-up period