The role of rest and stress cardiac energy metabolism and ectopic lipid deposition in diabetic cardiomyopathy

Thesis

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure and cardiovascular mortality even in the absence of coronary artery disease. Although the reasons for this are not clear, impaired cardiac high energy phosphate metabolism, coronary microvascular dysfunction and ectopic lipid deposition have emerged among the candidate mechanisms. Cardiac magnetic resonance imaging (CMR) and magnetic resonance spectroscopy (MRS) are powerful tools to characterise these conditions.

The findings here suggest that, in diabetes, coronary microvascular dysfunction may potentially exacerbate derangement of cardiac energetics under conditions of increased workload. The relationships amongst ectopic adiposity (myocardial, epicardial and hepatic), myocardial metabolic changes and left ventricular remodelling in T2DM were determined using proton magnetic resonance spectroscopy (¹H-MRS), cardiac computer tomography (CT) and multi-parametric liver MR. It was found that cardiac steatosis independently predicted left ventricular concentric remodelling and impairment of systolic strain in patients with T2DM. This work also demonstrated that ectopic adiposity is linked to insulin resistance, liver fibrosis and inflammation, and cardiac contractile dysfunction in diabetes, and that the coexistence of obesity and T2DM leads to higher epicardial fat volumes and significant non-alcoholic fatty liver disease compared to T2DM alone. These findings suggest that, since cardiac steatosis and ectopic adiposity are modifiable, strategies aimed at reducing myocardial triglyceride levels may reverse concentric remodelling and improve contractile function in the diabetic heart. The work on field strength effects on cardiac ³¹P-MRS has shown that 7T is feasible and reliable with reduced error and increased signal to noise compared to 3T.

In summary, the work in this thesis demonstrates the powerful role of CMR and MRS in elucidating the detrimental effects that originate from the metabolic abnormalities in the diabetic heart.

Authors: Levelt, E

• DOI: 10.5287/ora-6ryk58vge
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford