What we have learned and need to know about diabetes-related heart failure

Diabetes is one of Aotearoa’s fastest-growing health crises, and cardiovascular disease is its most lethal partner.

In Aotearoa New Zealand, diabetes affects about 350,000 people, with significantly higher prevalence and worse health outcomes for Māori and Pacific populations. Heart failure is now recognised as the most common cardiovascular complication of diabetes. Even when other cardiovascular issues are absent, such as high blood pressure or coronary artery disease, diabetes-specific changes in the heart can set the scene for the later emergence of heart failure.

Diabetes is more likely to result in a certain type of heart failure which is difficult to treat. It’s caused by impaired diastolic relaxation, and called heart failure with preserved ejection fraction. The heart pumps normally, but the heart muscle becomes stiff, is unable to adequately relax and fill with blood between beats, and ultimately delivers less blood to the body for each heartbeat.

Historically, most heart failure treatments have been developed to enhance the heart’s pumping action, rather than targeting the heart-filling phase.

A key problem is that the earliest symptoms of heart failure can be non-specific – shortness of breath, fatigue and exercise intolerance – making detection at this stage difficult. The gradual decline of exercise capacity may go unreported as patients adapt and attribute these symptoms to other causes such as ageing.

However, as heart failure symptoms progress, patients may gain weight, caused by fluid retention; experience shortness of breath when lying down; suffer ankle swelling; or wake from sleep with acute episodes of breathlessness. Each of these features relates to reduced heart function.

Maintaining heart health is therefore particularly important for people with diabetes. In most cases, they should be seen for two or more check-ups each year with a GP or diabetes physician, to identify and discuss the management of diabetes, other cardiac risk factors, and other diabetes-related conditions.

Ideally, these check-ups would also focus on any abnormal changes in fitness status, while promoting regular exercise, a healthy diet, avoiding cigarette smoking, vaping and illicit drugs, and reducing excessive alcohol intake.

But it is not all bad news. The latest diabetes treatments have been shown to provide some protection for the heart. In Aotearoa, empagliflozin (branded as Jardiance) is now prescribed as a second line treatment for type 2 diabetes.

The early clinical trials looking at the anti-glycaemic effect of empagliflozin serendipitously revealed that cardiovascular events and hospitalisations were lower in the treatment group, marking the first anti-diabetic drug to show such a strong cardiac benefit.

Pharmac has recently expanded funding for the use of empagliflozin for patients with heart failure. Having empagliflozin in the cardiology toolbox has been a game-changer for patients and clinicians, but there is still a long way to go to reduce early death and improve quality of life for people living with diabetes and heart failure. New treatments that specifically address the underlying causes of disease, rather than simply treating the symptoms, is of top priority for researchers in the field.

In the Cellular & Molecular Cardiology research group at the University of Auckland we have been investigating the molecular pathways that are affected by diabetes in the heart for over a decade.

We now know that heart failure in diabetes can be partly attributed to a failed pathway of glycogen processing. Glycogen is usually a carefully managed energy reserve within the heart muscle cells, but in diabetes, these sugar stores become excessive because an important breakdown process (glycophagy) isn’t working.

These new findings, which we published recently in Nature Cardiovascular Research, demonstrate that correcting this molecular pathway with gene therapy yields a remarkable rescue of heart function in diabetic mice. This translational discovery research has been funded by the Health Research Council NZ and the Marsden Fund NZ.

Future work will establish whether this unique therapeutic approach prevents progression to heart failure in diabetic patients.

It is our hope that these early-stage findings may one day translate into substantial life-changing treatments for the increasing population of people with diabetes in Aotearoa New Zealand.