Thanks to Diabetes Australia’s Millennium Research Award, Professor Merlin Thomas, head of the Biochemistry of Diabetes Complications Laboratory at Monash University, is researching an inhibitor which could help prevent and treat diabetes-related heart and kidney problems.

“My focus is on diabetic kidney disease and cardiovascular disease, which are both major killers of people with type 1 and type 2 diabetes,” he says. “I focus on ways to change the development and progression of these diseases in people with diabetes.”

Professor Thomas says diabetes is one of the leading causes of cardiovascular disease. “It affects the cells lining the blood vessels that control oxygen delivery to the heart. When these cells become dysfunctional, there’s an increased risk of heart attacks and heart failure. In an NSW study, at least a third of people coming into hospital with fluid overload and heart failure had diabetes. It’s a driver of heart failure, heart attacks and premature mortality.”

Kidney failure is also a big problem in people with diabetes. Professor Thomas says in Australia, at least half of the people with type 2 diabetes who see their GP have evidence of kidney damage. “This is because either their kidneys aren’t filtering properly or they’re leaking increasing amounts of albumen into the urine.”

Professor Thomas’s research focuses on the key mechanisms through which people with diabetes develop heart and kidney problems. “It’s been recognised for a number of years that a particular protein in the body, the receptor for advanced glycation end products (known as RAGE), seems to drive inflammation in the heart and the kidneys, which leads to both cardiac and kidney damage,” he says. “Controlling blood glucose, blood pressure or cholesterol is not enough to stop the damage. So, we’ve been trying to develop a new way of targeting this pathway.”

Professor Thomas’s team are now building inhibitors that block this pathway. He was awarded the prestigious Diabetes Australia Research Program Millennium Research Award in 2019 to do further research on these inhibitors and has spent two years testing their effectiveness in animal models.

“It was a great honour to receive the award and it was also a great boost for us,” says Professor Thomas. “It has helped us to start a new company to commercialise the discoveries we’ve made around RAGE and it helped us to secure another grant last year to get us that little bit further down the research track. Winning an award like this gives us enormous leverage, so thank you, Diabetes Australia.”

Professor Thomas says the aim is for his research to eventually lead to a new therapy for people with both type 1 and 2 diabetes that will be easy to use and long-lasting.

He says for him, the most important thing in diabetes management is reducing diabetes-related complications. “Diabetes is only as bad as the complications that it causes,” he says. He says many people with diabetes are healthier than the general population and have better outcomes because they look after themselves. “Those people with diabetes whose lives are shortened and whose quality of life is reduced, it’s largely due to things like eye, heart and kidney disease.”

Professor Thomas says improving glucose control is not enough to reduce these complications. “We’ve seen a number of good glucose-lowering trials and still you don’t see less blindness or fewer amputations or kidney failures. So, we need to do more in direct therapies that target these complications. If you could prevent these complications from occurring, maybe it wouldn’t be as necessary to control blood-sugar levels as vigorously.”

He says eliminating these complications is going to be a “long, hard road” but significant progress is being made. “With new agents, we’re slowing the progression of kidney disease and reducing the risk of serious cardiac outcomes. I’d like to see both these complications eliminated.”