100 years of diabetes research: Building on Banting’s legacy

Dr. Frederick Banting’s discovery of insulin began with an idea he had as a young doctor and instructor at Western University in London, Ontario.

On October 31, 1920, Banting had just prepared a lecture about the role of the pancreas in digestion and regulating blood sugar. That night, he woke up from a dream and wrote down a hypothesis that became the catalyst in the discovery of insulin.

Carrying on Banting’s legacy, the ongoing, collaborative work of London’s research-intensive institutions and hospitals is paving the way for innovation in diabetes research, education and care.

Genetics maps end of the road for diabetes

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 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.

“Research shows it’s usually a combination of multiple genetic factors, many small defects, scattered throughout the genome, all culminating to create risk.”

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 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, a researcher with a singular focus on the miniscule, is making all of the right moves.

Patient-centred approach key to diabetes management

When it comes to effective diabetes patient care, health experts must look beyond the clinics and clinical trials.

It’s a revelation from research conducted by endocrinologist Dr. Kristin Clemens, which identified the socio-economic challenges confronting patients while managing their diabetes and advanced kidney disease.

“Many patients in our study came from lower-income backgrounds, so it can be difficult for them to pay transportation and parking costs for medical appointments,” says Clemens, a clinician-researcher at St. Joseph’s Health Care in London. “It can also be challenging to take time out of their workday to see specialists for their various health conditions.”

Researchers have made significant strides in improving quality of life for people with diabetes. New medications and technologies—like insulin pens that connect directly to smartphones—have made self-guided disease management easier for these patients. But research has historically focused on treatments for patients in the earlier stages of diabetes, and fewer studies address best practices for those with later-stage diabetes living with multiple health complications. These comorbidities typically exclude patients from clinical trials and research studies, limiting foundational research for this patient population.

Aiming to change that dynamic, Clemens has focused her research on diabetes patients with comorbidities, or additional medical conditions, including advanced kidney diseases.

Clemens recently examined diabetes care in a population-based study of more than 4,000 Ontarians with diabetes undergoing dialysis treatment for kidney disease. Over a two-year period, the study found 40 per cent of patients experienced a gap in their diabetes care, a disconnect between best practices and their actual quality of care.

Her team then conducted a qualitative, patient-oriented study to uncover the factors contributing to those gaps. This work revealed several unique challenges patients faced while managing diabetes and advanced kidney disease. The cost of transportation and parking, and taking time away from work are factors that are preventing patients from accessing diabetes care. Many patients also voiced a desire for professional help in coordinating their diabetes care.

Building on these insights, Clemens’ team implemented a diabetes outreach program in the dialysis unit at London Health Sciences Centre’s Kidney Care Centre. Led by a diabetes educator, the program offers health management assistance to patients with diabetes while they receive dialysis treatment. The educator helps patients stay on schedule with insulin shots and other medications. They also remind patients to have screenings conducted in optometry and podiatrist units to help prevent impaired vision and foot ulcers that may result from increased blood sugar.

To ensure consistent care, the educator communicates regularly with the patient’s nephrologists, family doctors and endocrinologists. Clemens says the program has improved the patients’ self-management skills, blood sugar levels and overall satisfaction with their level of care.

Clemens hopes her team’s research will support similar programs for patients living with diabetes and comorbidities.

“Before we pour our dollars into clinical trials, it’s essential to understand what matters to patients,” she affirms. “Through this work, I’ve developed an even deeper understanding of what my patients experience on a daily basis, and that has transformed how I practice as a physician. I hope this research helps emphasize the importance of patient-centered efforts to improve the health and quality of life of all patients with diabetes.”

Pausing the diabetes puzzle

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.

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.”