Metabolic and functional evaluation of diabetic cardiomyopathy using MR Spectroscopy and MR Imaging

Bizino, M.B. (2022)

Doctoral Thesis

Patiënts with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure: diabetic cardiomyopathy. This condition is characterized by a thickened cardiac muscle of the left ventricle that impairs its adequate filling with blood. The cause of diabetic cardiomyopathy is probably related to insuline resistance and impaired cardiac energy metabolism by accumulation of toxic lipids in the cells of cardiac muscle. Magnetic resonance (MR) imaging and MR spectroscopy of the heart can be used to characterize and investigate diabetic cardiomyopathy and its treatment.

This thesis describes studies aimed at improving MR techniques on the one hand. While, on the other hand, MR is applied to investigate the efficacy of pharmacologic and lifestyle interventions to treat diabetic cardiomyopathy. The effect of the diabetes drug liraglutide on diabetic cardiomyopathy was studied in a randomized placebo-controlled trial. Liraglutide reduced filling pressure of the left ventricle, which in time could be a beneficial effect in terms of preservation of cardiac health. In addition, it was found that liraglutide did not reduce ectopic fat accumulation in visceral abdominal fat, the liver and the heart, despite significantly reduced body weight as compared tot the placebo-treated group.

Furthermore, the effect of a lifestyle intervention aimed at healthy nutrition and physical exercise was investigated in patients with insulin-dependent T2DM. In twelve weeks, patients required less insulin, and fat accumulation in the liver and heart was significantly reduced. Despite these improvements, the endogenous insulin-production and heart function did not change. These results suggest that these patients with T2DM had irreversible end-organ damage.

In conclusion, this thesis shows that the application of advanced MR techniques can help to better understand diabetic cardiomyopathy and its treatment. Thereby hopefully leading to an improved cardiovascular prognosis of patients with T2DM.

• Type 2 diabetes mellitus
• Left ventricular diastolic dysfunction
• Ectopic fat accumulation
• Glucagon-like peptide-1 receptor agonist
• Cardiac proton magnetic resonance spectroscopy

• All authors: Bizino, M.B.
• Supervisor: Lamb, H.J.; Smit, J.W.A.
• Co-supervisor: Jazet, I.M.
• Committee: Pereira Arias, A.M.; Leiner, T.; Westenberg, J.J.M.; Duijvestijn, P.H.L.M.; Pijl, H.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-11-16
• ISBN (print): 9789463617574