Altered myocardial calcium-handling in patients with diabetes mellitus or heart failure (Dr Shruti Joshi)

In patients with diabetes mellitus, cardiovascular disease and heart failure associated are the leading causes of complications and emergency admissions in the United Kingdom with an increasing role played by diabetic cardiomyopathy.

Impaired calcium handling appears to be one of the causal mechanisms of impaired contractility associated with diabetic cardiomyopathy and heart failure.

Sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy reduces heart failure hospitalisations and death in patients with type 2 diabetes as well as those with heart failure.

The mechanism of how SGLT2-inhibition improves outcomes is unknown and appears to go beyond its glucose-lowering and diuretic effects.

We have recently developed a non-invasive method of measuring myocardial calcium handling with manganese-enhanced magnetic resonance imaging.

In early pilot studies, we have demonstrated marked alterations in calcium handling in patients with cardiomyopathies and those with diabetes mellitus.

In this fellowship, we will explore the role of myocardial calcium handling in patients with diabetes or heart failure and, in a randomised controlled trial, investigate the effects of SGLT2-inhibiton.

This will enhance our understanding of the aetiology, progression and treatment of diabetes and heart failure that could inform the application and development of novel therapies for these conditions.