Understanding diabetes, one heart cell at a time

Julia Musgrave remembers sitting in a lecture theatre as a first-year engineering student, listening to a biomedical engineering researcher named Nic Smith describe how complex mathematical computer models of individual human hearts would one day help doctors better understand disease and test treatments.

The idea stuck.

Today, Professor Smith is the Vice-Chancellor of Waipapa Taumata Rau, University of Auckland.

Meanwhile Musgrave, now Dr Musgrave and working at the University’s Auckland Bioengineering Institute, has been awarded funding to continue the bioengineering vision. 

Musgrove’s PhD and postdoctoral research has seen her investigate what happens to heart muscle when people develop type 2 diabetes. Her research combines laboratory experiments on tiny pieces of donated heart tissue with complex mathematics and physics modelling. The aim is to uncover changes that may help explain why people with diabetes are more likely to develop heart disease. 

The work forms part of ABI's long-running programme to build computer models of the human body and, eventually, personalised ‘digital twins’ for patients.

Now, support from a prestigious $265,000 Auckland Medical Research Foundation (AMRF) First Fellowship will see Musgrave spend the next two and a half years investigating how type 2 diabetes changes the behaviour of heart cells, research she hopes will help make those bioengineering digital heart models even more powerful and personalised.

It’s a natural fit for someone who was a maths whizz, even at school.

"I didn't always love it, but it always came easily," says Musgrave. "By the end of high school, I realised it’s not just fun, it’s the thing I want to do."

That led to Nic Smith’s lecture and eventually bioengineering and heart research.

"I love solving problems with maths and it's nice to actually apply it to something that's going to help people."

Tiny pieces of heart

Type 2 diabetes affects hundreds of thousands of New Zealanders and is a major risk factor for cardiovascular disease. Yet many questions remain about what diabetes is actually doing to the heart itself.

During her PhD, Musgrave worked with tiny pieces of heart tissue donated by patients undergoing cardiac surgery at Auckland City Hospital. She measured how heart muscle from people with diabetes behaved compared with tissue from people without the condition.

What she found was intriguing.

The diabetic heart muscle contracted more slowly and with less force than non-diabetic tissue. But it also appeared to use less energy.

"We know people with diabetes are more likely to have heart complications, but we're still trying to understand the mechanisms that sit underneath that." 

Rather than stopping at the laboratory bench, Musgrave then used the measurements to build mathematical models of how individual heart cells in people with and without diabetes behave during a heartbeat.

"The models allow us to predict things that we could otherwise not measure, or otherwise would be really hard to figure out," she says.

Personalised treatment

While digital twins may sound futuristic, Musgrave says elements of the technology are already being used internationally.

Drug companies currently use computer models to help predict whether new medicines could trigger dangerous heart rhythm abnormalities.

The long-term ambition is much broader.

One day, digital heart models may help doctors understand how an individual patient is likely to respond to different treatments – before they are prescribed.

At present, finding the right medication often involves a degree of trial and error. This is particularly the case with patients with type 2 diabetes and heart disease because of the complex interaction between the two conditions.

The hope is that digital twins could help identify more specifically what is going wrong in the diabetic heart and look at new targets for future therapies. Later, personalised models using medical and other data from a particular patient could identify which treatments are most likely to work for them.

“We could use a personalised model to say ‘If we applied this to you specifically, is it going to improve your heart function the way we expect it would?’”

The ultimate goal is not simply a better understanding of diabetes, but better outcomes for the people living with it, Musgrave says.

She also hopes the work can contribute to more equitable healthcare. Part of the fellowship grant will be used to help develop models that reflect the diversity of New Zealand's population, including Māori and Pacific communities, who experience disproportionately high rates of diabetes and cardiovascular disease.

Auckland Bioengineering Institute director Professor Merryn Tawhai says early career researchers having access to funding to continue their work is critical if New Zealand is to continue to be at the cutting edge of human digital twin research internationally.

“Great scientific breakthroughs often begin with simple curiosity,” she says. “Julia’s research comparing healthy and diabetic heart tissue is now paving the way towards digital solutions that will ultimately lead to faster, more effective patient care.” 

Musgrave says the Auckland Medical Research Foundation fellowship gives her a chance to continue pursuing the idea that first captured her imagination as an undergraduate: using mathematics to improve lives.

"I want to do work that's fun," she says. "And I also want to do work that will one day help people."