Advancing
diabetes research and care

Type 2 diabetes is a life-altering disease. And it’s known to cause 30 per cent of Canada’s strokes and 40 per cent of the country’s heart attacks.

Can it be cured? Not yet. But every day, Dr. Robert Hegele works with patients to improve outcomes, reduce risks and discover the disease before it takes hold.

As one of the world’s leading authorities on cholesterol, Hegele routinely advises patients on how they can live longer and reduce their risk of serious health issues. Among the more than 2,500 patients in his care, he has noticed that when a patient has diabetes and high cholesterol, a hazard warning starts flashing on their risk of suffering a stroke or heart attack.

The good news, he says, is that it’s entirely within their power to fight the risk.

In the lab, Hegele targets one tiny molecule at a time and moves one step closer to preventing the onset of diabetes.

“We used to have this idea that there’s one gene responsible for diabetes, but it’s not quite that simple,” says Hegele, an internationally renowned endocrinologist and the medical director of the London Regional Genomics Centre. It’s at the Centre where his team studies the variants in the genetic code that can cause diabetes and cholesterol disorders.

A pioneer in developing diabetes medications, Hegele has used innovative treatments and game-changing technologies for patients with Type 2 diabetes at London Health Sciences Centre throughout the course of his award-winning career.

Using a diagnostic DNA panel that his lab invented, Hegele has discovered causal genes and mutations for more than 20 named medical conditions, including several inherited forms of diabetes.

His lab has shown that, in some cases, a single misprint in the DNA barcode is all that it takes to explain why a patient has diabetes. In most other cases, diabetes occurs because of the concerted effects of many genetic variants scattered throughout the patient’s genome.

He believes these human genome mapping efforts will provide even better understanding to why some people either can’t produce insulin or can’t properly use the insulin their bodies produce. Future advancements, Hegele says, will include better definition of diabetes subtypes, discovering targeted new treatments and even gene editing.

No matter what he finds, Hegele acknowledges for many patients with a genetic predisposition to Type 2 diabetes, environmental and lifestyle factors can contribute ultimately contribute to developing the disease. Many patients with diabetes also become susceptible to high cholesterol, which triggers the growth of fatty deposits in blood vessels. That in turn makes it difficult for blood to flow through arteries or – worse – the fatty deposits can break suddenly and form a clot, possibly causing a heart attack or stroke.

“In a patient with diabetes, treating cholesterol is almost as important as treating blood sugar. The complications we’re trying to prevent are things like amputations, strokes and heart attacks. We need to multi-task when managing genetic cardiovascular risk in patients with diabetes,” explains Hegele, a distinguished professor of medicine and biochemistry at the Schulich School of Medicine & Dentistry.

Preventing Type 2 diabetes, and one day eradicating it, is a complicated game. But Hegele, the world-class Western researcher with a singular focus on the miniscule, is making all of the right moves.

Dr. Irene Hramiak isn’t ready to say they’ve found a cure for a Type 2 diabetes just yet. But the renowned endocrinologist and her collaborators are developing new treatments that may force the disease into remission, and for now, she’ll take it.

A professor of endocrinology and metabolism at Western’s Schulich School of Medicine & Dentistry and a doctor at St. Joseph’s Health Care London, Hramiak has led or co-led more than 50 clinical research trials for people whose lives have been altered instantly by a diabetes diagnosis.

Ordinarily, doctors prescribe lifestyle changes, such as diet and exercise, until the disease progresses and additional medications are added – ultimately, to the point where insulin is required. Hramiak’s trials explore whether it’s possible to ‘reset’ the pancreas from the beginning – to slow down the progression – by starting with an intensive course of insulin and medications at the outset, in addition to conventional lifestyle changes.

“We’re seeing if we can cause a remission – we can’t call it a cure – in people who are newly diagnosed by changing the way we treat the disease from day one,” explains Hramiak.

The research is collaborative and cumulative, and Hramiak says even trials that don’t meet the desired results are considered a success.

“You have to keep asking the questions and keep doing the work. It’s bit-by-bit, step-by-step, and everybody adds their piece to the puzzle,” she says.

Interlocking steps

Greg Ackland added one of the pieces.

With a family history of diabetes, Ackland knew his turn wasn’t a matter of if, but when. So when he was diagnosed with Type 2 diabetes in his forties, he was already prepared for what was to come. Over the years, Ackland watched his family members’ disease progress and their reliance on medications and insulin steadily increase.

“I couldn’t see any way out,” he said. Enter Dr. Hramiak.

Ackland enrolled in one of her clinical trials, and his treatment – and more importantly, his outlook – changed. Hramiak’s game-changing approach to treatment put Ackland’s disease into remission, completely eliminating the need for any diabetes medication for more than a year after the trial ended.

“If I was offered a chance like that again, I would jump at it,” he says. “I know that by being involved in research, it’s benefitting others, and advancing the care of diabetes.”

Growing up, Dr. Subrata Chakrabarti watched his father struggle with Type 2 diabetes. The experience led him to medical school, where he set his sights on gaining a deeper understanding of the disease, its complications and effective treatments.

“If we can learn more about the pathways that lead to the development of a disease, we can develop more effective treatments,” says Chakrabarti, a physician and professor at Western’s Schulich School of Medicine & Dentistry.

During the past three decades, Chakrabarti’s expertise and passion for studying disease at the molecular level have fueled breakthrough research in diabetic retinopathy treatment.

Chakrabarti and his team have made significant inroads in what they hope will result in more efficient and early diagnosis of retinal damage, as well as the development of potential treatments for diabetic patients.

In one of many offshoot projects, Chakrabarti’s lab focused on the damage sustained by endothelial cells, which line blood vessels in the retina (nerve tissue in the back of the eye), when the blood in the vessel has high glucose levels. The damaged blood vessels bleed, causing other tissue damage, subsequently leading to blindness.

In patients with diabetes, high glucose levels in the endothelial cells activate a complex network of non-coding RNAs, which subsequently impacts protein production inside the cell. Non-coding RNA molecules have been recently discovered and have a major role in regulating damaging protein production. They are also known as ‘dark matter genome’, explains Saumik Biswas, PhD’20, who worked in Chakrabarti’s lab as a graduate student. He has since founded Tenomix, an early-stage medical technology company, where he is now CEO.

“The problem is that these cells are not accustomed to the large amount of diabetes-related protein molecules being produced, which starts a destructive chain reaction that can lead to cellular dysfunction and tissue damage,” he explains. “When such damage occurs in the retina, a condition we call diabetic retinopathy, blindness and other complications result.”

While most diabetes literature and treatments focus on targeting the proteins that wreak havoc in a diabetic patient, Chakrabarti’s lab remains intent on tackling the mechanisms even closer to the root of the problem.

“We’re now focused on how non-coding RNAs respond in high-glucose environments,” Chakrabarti says. “Why are they producing these proteins that the cell does not need? Ideally, if you can identify and then block a specific non-coding RNA, you can block multiple abnormal changes in the cell.”

Although many research teams are examining the role of non-coding RNAs in cancer care and diagnosis, few have managed to translate this foundational research into treatments for diabetic patients.

One of the ongoing projects at Chakrabarti’s lab involves collecting blood from both diabetic and non-diabetic patients to compare the levels of nine distinct non-coding RNA in each. By analyzing the behaviour of these non-coding RNAs in both high-glucose and normal glucose environments, the researchers can start to pinpoint some of the early indicators that a patient may develop tissue damage.

In the past, therapies for diabetic retinopathy have focused on reactive rather than preventative treatment. “With existing diagnostic methods, it’s challenging to identify a problem until major tissue damage has already happened,” explains Biswas. “Our ultimate goal is to provide patients with something that can help prevent damage and grant them a better quality of life.”

A major milestone in the evolution of diabetes care in London began 50 years ago with two visionaries and a forward-thinking hospital led by the Sisters of St. Joseph.

Drs. Wilson Rodger and Gerald Tevaarwerk, physicians at St. Joseph’s Hospital, recognized that medical treatment was not enough to manage diabetes. Patients needed to take charge of their own health and be partners in their care.

At the time, St. Joseph’s was testing its wings as an academic hospital. There was zeal to explore new projects, new ways of caring for patients. Until then, “patients learned what they could from their family doctor, did what they were told and hoped for the best,” recalls Rodger.

But in 1970 when head nurse Fran O’Brien began began delivering lectures to diabetes patients inside a four-bed endocrine evaluation unit, the seeds for an education centre were planted.

“The hospital allowed the wheels to turn,” says Rodger.

The St. Joseph’s Hospital Diabetes Education Centre opened in 1973 with Rodger and Tevaarwerk leading the charge. It was initially funded through donations from London’s Lawson family, the local branch of the Canadian Diabetes Association, the hospital’s Medical Staff Association and the May Court Club.

Its first coordinator was nurse educator Dorothy Gibson, a pioneer in her own right. Gibson was the first person with insulin-dependent diabetes to be accepted into nursing, and she had a well-known motto: “The diabetic that knows the most, lives the longest.”

The Centre would grow quickly and eventually move to Mount St. Joseph to accommodate growing demand, which increased from an annual total of 402 patients in 1973 to 400 patients per month by 1989 the year the program moved.

Insulin pumps were introduced in the late 1970s, through a clinical trial headed by Rodger and Dr. John Dupre at London Health Sciences Centre’s University Hospital. They would have the first pump patients outside the United Kingdom, and play a key role in the evolution of the insulin pump as an effective treatment to reduce diabetes complications.

Subsequent advances in diabetes management have changed the care journey and quality of life for patients, but the opening of the Diabetes Education Centre (DEC) of St. Joseph’s Health Care London, as it is now known, remains one of the most significant milestones for London.

Today with 12,000 patient visits annually, the DEC, which returned to St. Joseph’s Hospital in 2008, boasts a dedicated team of 16 certified diabetes educators (eight nurses, seven dietitians and one pharmacist), as well as support staff.

The continuous advent a of diabetes technologies – insulin pumps, glucose meters and sensors – as well as new therapies and treatments, means learning remains a constant for diabetes educators and the people they serve.

“The Diabetes Education Centre is still at the forefront,” says Rodger. “The wheels are still turning.”

Monitoring glucose levels and taking daily insulin shots will be a thing of the past for diabetes patients if David Hess sticks the landing.

As the Sheldon H. Weinstein Chair in Diabetes Research at Western University, Hess pushes the boundaries of diabetes care, management and treatment for the more than 422 million afflicted globally with the disease. Currently, he’s advancing stem cell research by identifying, which proteins are essential to islet regeneration, and which human building blocks are most efficient for creating those proteins.

“My goal is to use stem cell therapy for helping the body heal itself naturally rather than relying on temporary external treatments,” says Hess.

Navigating autoimmunity, the body’s natural defence against foreign cells, remains the most significant barrier to successfully using stem cell therapy as a treatment for Type 2 diabetes. Hess and his research team have already shown the role stem cells play in regeneration. Now, they’re working hard to find a way to dampen autoimmunity, so the body doesn’t attack healthy, regenerated cells.

“We discovered that what stem cells produce is far more important than what they actually become,” Hess explains. “The proteins they generate are what really stimulate the regenerative process.”

Finding Final Pieces

Keeping the immune system away from regenerated cells is only half the puzzle. Hess and his collaborators must also find ways to keep the cells alive, as they don’t survive very long in an oxygen-deficient environment.

Tapping into the wealth of expertise at Western, Hess enlisted the help of Lauren Flynn, who specializes in bioengineering, to drive his research forward. Flynn generates decellularized adipose tissue, which is tissue with everything removed but the structural cells.

“My team uses that material as a scaffold to grow and sustain new cells, allowing us to make substantial progress,” says Hess.

The award-winning Western researcher is also collaborating on clinical trials, based at the University of Toronto, focused on fine-tuning diabetes medications.

“We’re examining how these new medications can impact the circulating level of pre-existing stem cells in the blood,” he says. “There is significant potential to leverage a patient’s own stem cells to help prevent cardiovascular complications, especially in patients with Type 2 diabetes.”

Although it could be years before his research translates directly into therapeutic treatments, Hess is optimistic for the future.

“It’s an honour to learn from and contribute to stem cell research that’s internationally renowned and making huge strides to improve the well-being of diabetic patients,” he says.