This Issue

It saved lives, sparked careers and drove a century of science — the discovery of insulin has had an unquestionable ripple effect on the world.

The Nobel Prize winning breakthrough from 1921 is well-entrenched in Canadian history.

But, there remain many unknowns about insulin — and diabetes.

There are also huge hurdles in addressing the disease, from social disparities among those affected to the uneven cost of insulin to the complexity of lifelong treatments.

Technological and medical innovations hold tremendous promise. So do individualized approaches that recognize each person will manage diabetes differently.

There is also a growing awareness of the need to address systemic factors that influence the onset and course of the disease.

These areas, say researchers, clinicians and patients, will drive the future of diabetes care and discovery.

Issue
Highlights

The Enduring Impact of a Discovery

The Uneven and Heavy Price of Insulin

Whither the Cure

Photo Collage Source: NASA

By Paul Fraumeni

It was 1983.  

Janet Rossant was 33 years old.  

Six years earlier, she left her native England with degrees from Oxford and Cambridge. She had landed a position at Brock University, across Lake Ontario from Toronto, in St. Catharines.  

An assistant professor of biology, she headed a laboratory team seeking to understand how the embryo develops. To do that, the Rossant team was starting to develop transgenic mice.  

“This was a new field of developmental biology, and we were excited by the possibility of being able to add genes to embryos and study their effect on development. But to do this research, we needed specialized equipment and we also needed the money to buy it,” she says.

Rossant applied to the Banting Research Foundation (BRF), which awarded her $25,000 — not a huge amount, but an important influx of financing to a researcher starting to build a track record.  

“People like to talk about the tipping point,” she says. “When you’re a young investigator and you don’t have a lot of funding, it’s hard to move to the next level. So, the Banting Foundation was then and still is a really important support for new investigators, providing that critical piece of funding just when you need it.”

That early support paid off for Rossant — and for global society.  

By 1985, Rossant had moved to the University of Toronto and the Samuel Lunenfeld Research Institute (known today as the Lunenfeld-Tanenbaum Research Institute) at Mount Sinai Hospital, only two years after receiving the BRF grant.

Over the next 30 years, Rossant — who is now the President and Scientific Director of the Gairdner Foundation — conducted research that earned her renown and a bevy of awards for her work on genetics and stem cells.

Today, Rossant is a University Professor in the Department of Molecular Genetics at the Temerty Faculty of Medicine, and a Senior Scientist and Chief of Research Emeritus at the Hospital for Sick Children. 

So, how does the discovery of insulin decades before relate to Rossant’s work?

In 1921, sixty-three years before Rossant applied for that grant, an unlikely team was hard at work in a U of T lab on a disease — diabetes — that had killed millions over the centuries and continued to bewilder scientists.  

Frederick Banting (MD 1916), a GP with little research experience, and Charles Best, a medical student, were working from an idea Banting had about how to isolate the mysterious secretion of the pancreas that controlled metabolism.  

U of T’s then chair of physiology, Professor J.J.R. Macleod, somewhat reluctantly gave the team lab space, equipment and dogs to use for testing.  

Banting’s idea worked. 

The discovery won the Nobel Prize and continues to enable people with type 1 diabetes to live full, rich lives — an unthinkable outcome prior to the team getting down to work in 1921.  

That innovation would have been quite enough. 

However, it has acted as a catalyst to stimulate a century of medical research in a dizzying array of areas that continue to have an enduring impact. And, an important generator of that research came from the creation of two foundations established in the spirit of Banting and Best.  

A fundraising campaign that raised $500,000 founded the BRF in 1925. A large bequest in 1948 added to the endowment.  

“Our mission is to fund young investigators, the future Bantings and Bests, in the way they were funded by Macleod, at the beginnings of their careers when they have a bold idea that just might move society forward,” says Professor Catharine Whiteside (BSc ’72, PhD ’84, MD ’75, PGME ’83), BRF chair, Former Dean of Medicine and an Emerita Professor with the Department of Medicine. 

Then in 1960, W. Garfield Weston Foundation funding established the Dr. Charles H. Best Foundation. The original idea was to support research at the discretion of Professor Best (MD ’25), who went on to conduct important studies in a number of areas and become a U of T research leader.  

When Best retired in 1965, the funds were designated to U of T’s Banting and Best Department of Medical Research. That unit became part of the Donnelly Centre for Cellular and Biomolecular Research at U of T.

“Today, those funds are used to support researchers getting started on their careers through a program called the Dr. Charles H. Best Postdoctoral Fellows,” explains Professor Peter Lewis, the program’s Board Chair and former Chair of the Department of Biochemistry at U of T. “This funding enables us to help researchers of a high calibre from around the world to pursue their ideas and to learn with the scientists of the Donnelly.”

These two foundations have helped to start remarkable careers.  

“The influence of Banting and Best goes way beyond diabetes and insulin,” says Professor Reinhart Reithmeier, also a former Chair of the Department of Biochemistry at U of T and winner of a Best Postdoctoral Fellowship when he was a U of T fellow in the late 1970s.  

Indeed, early BRF recipients comprise a community of young researchers who went on to be superstars. Among them was Gordon Murray (MD 1921), who the BRF awarded funding from 1937 to 1939. 

He was one of the first researchers in the world to show how the drug heparin is effective in preventing thrombosis and embolism. Murray also developed the first artificial kidney to be used successfully in North America.  

A short time later came William Mustard (MD ’37), who the BRF awarded funding to in 1950. He created the “Mustard Operation” that is still used worldwide. The surgery corrects a complex defect in “blue babies” — infants born with the arteries and veins to and from the heart connecting with the wrong heart chambers.  

Then there was Henry Friesen (Hon ScD ’00), awarded funding from 1972 to 1973, whose research on human growth hormone made possible successful replacement therapy in hormone-deficient children.  

The Toronto insulin discovery continues to ignite important ideas from newer generations.  

At the Donnelly, the 2019 Best Postdoctoral Fellow Juline Poirson is studying the ubiquitin-proteasome system (UPS). It is critical in ensuring the normal functioning of cells, notably by destroying proteins that are no longer needed. But in diseases such as cancer, the UPS is dysregulated. 

Poirson is working to understand why this happens with certain proteins. Her work could lead to important drug developments to treat diseases like cancer. 

“I came from France to the Donnelly because I knew it would help me build on what I had already learned,” she says. “It is one of the best research centres in the world when you work on protein-protein interaction. This experience is going to help me for the rest of my career.” 

At York University, Professor Ali Abdul-Sater (U of T Postdoctoral Fellow ’16) is an assistant professor in the Faculty of Health.

BRF funded Abdul-Sater in 2018, enabling him to delve deeper into his focus: how abnormal inflammation is at the core of rheumatoid arthritis. 

His specific interest is in exploring how TRAF1, an immune signalling molecule, can control inflammation. Abdul-Sater’s team has proven that people with a genetic variation in their TRAF1 make less TRAF1 protein, which increases their risk of developing rheumatoid arthritis.  

But adjusting or removing TRAF1 is dangerous because the protein plays other vital roles in our immune system. Finding the solution is Abdul-Sater’s next research project. 

“I wouldn’t have come this far without the Banting support,” he says. “As a new investigator, I couldn’t get funding because I couldn’t get the funding I needed to do certain experiments in the area of inflammation. It was a catch-22 predicament. Our work now has close to $2 million in grants. It all started with the Banting funding.”  

At SickKids Hospital, Professor Nomazulu Dlamini (PGME ’11) is an associate professor of pediatrics at the Temerty Faculty of Medicine. The pediatric neurologist and scientist specializes in understanding and treating strokes in children.  

Her focus is dystonia, a disabling and painful disorder that can occur in children who have experienced a stroke. It’s characterized by involuntary, repetitive muscle contractions, twisting movements and abnormal posturing. Often, it is resistant to treatment.  

It is thought that the problem originates in the basal ganglia, a network in the brain. Dlamini’s lab is studying the differences in the neural network between childhood stroke patients who have dystonia and those who don’t. Understanding why some children experience dystonia will increase the potential of developing effective therapies.

The BRF awarded Dlamini $25,000 in 2018 to support her work in understanding dystonia. 

“That support has been very helpful. With the pilot data from the work we have been able to get because of the Banting funding, we’ve been able to leverage that for further funding,” says Dlamini. “That’s all because Banting believed in our idea of discovering why there is this difference between these two groups of children.”

Which researchers will the two foundations support next?  

That remains to be seen, but Rossant, who was Chief of Research at SickKids for 10 years, is adamant that seed funding for researchers at the beginning of their careers is vital in creating new knowledge and applications that will improve health.  

“My most important duty at SickKids was to encourage researchers, particularly young researchers, to help them set up their careers with equipment, infrastructure and mentoring, and provide them with a collaborative environment in which they could grow,” she says. 

“And that meant helping them get the money they needed, which is why these foundations are so important. They are focused solely on enabling young researchers to get started.”  

Reithmeier emphasizes that the model the Banting and Best foundations use today is the same type of support U of T provided for insulin research in 1921 — getting young researchers the funding they need to pursue their curiosity.

“Frederick Banting had a great idea. Actually, it was a crazy idea,” says Reithmeier. “But, those are the ones that we have to fund.” •

Collage by Leanne Inuarak-Dall

By Ishani Nath

Rick Bhurji (BA ’92) was shocked to learn that at age 47, he had type 2 diabetes.

His next thought was: What did I do wrong?

Rick’s daughter, Anjali, noticed that many of their Indo-Canadian friends and family had “mysteriously” developed diabetes.

She figured her father’s diabetes was due to his love of pop and junk food. “For many of us who are South Asians, we internalize and blame ourselves for the diabetes epidemic in our community, but that is really unfair,” says Professor Ananya Banerjee (MSc ’07), an assistant professor at the University of Toronto’s Dalla Lana School of Public Health and a researcher with the Temerty Faculty of Medicine’s Banting & Best Diabetes Centre.

In fact, people from communities of colour across Canada are at higher risk for diabetes. The incidence rate of type 2 diabetes is double in Black communities and triple in South Asian and First Nation communities, compared to white Canadians.

A recent report found that First Nations children in Manitoba are 25 times more likely to be diagnosed with type 2 diabetes than other children. But disparities in diabetes are about more than ethnicity.

Researchers have found that location, income level, education, mental health, and experiences of racism and trauma can all profoundly impact the development and progression of diabetes.

By looking beyond basic biology, health care providers are not only identifying which communities are at risk for diabetes, but also what interventions can make a difference.

“In health care, we tend to take a one-size-fits-all approach,” says Professor Aisha Lofters (BSc ’00, PGME ’06, PGME ’08, PhD ’12), a clinician scientist and an associate professor of family and community medicine at the Temerty Faculty of Medicine.

Lofters is also co-leader on the BETTER WISE project to improve the screening and prevention of cancer and chronic illnesses, including diabetes.

In practice, set guidelines and flowsheets don’t work for all individuals, explains Lofters.

Rather than “wagging the finger” at a patient who, for instance, isn’t meeting the recommended amount of exercise, the BETTER WISE project works with the patient to set individualized, attainable goals — such as going for a 15-minute walk each week.

Banerjee took a similar approach with the South Asian Adolescent Diabetes Awareness Program (SAADAP), providing education and prevention strategies to 80 South Asian teens with a family history of diabetes.

Through this pilot program, about eight in 10 participants reduced their intake of sweets and junk food, and encouraged their family members to eat healthier.

Anjali and Rick, for instance, learned recipes for a healthy mango lassi and chickpea salad that have become staples in their home. Outcomes of tailored diabetes programs are promising, but as obesity management expert Sean Wharton (BSc ’92, PharmD ’97, MD ’01, PGME ’04) explains, they point to larger flaws in Canada’s health care system.

“Disparity has come about because of a health care system that isn’t serving people of colour,” says Wharton.

Beyond adjusting care to fit individual patient needs, he says some of the most effective ways of treating disparities in diabetes are at the grassroots level, such as in places of worship and community centres.

“These are spaces where the people working with the community are not biased against them, and they’re not blaming and shaming them, making them feel unrecognized or discriminated against,” explains Wharton.

In an effort to dispel internalized blame or stigma related to diabetes, Banerjee, through SAADAP, highlights the social determinants of health, such as the walkability of neighbourhoods and the burden of precarious employment, and how they affect the participants’ health.

Those lessons made Anjali realize, “There’s no need to feel horrible, and that you caused this, because you didn’t.”

Recent findings from the Manitoba Centre for Health Policy and the First Nations Health and Social Secretariat of Manitoba (FNHSSM) showed that First Nations individuals access primary care at a similar rate to others in the province. However, that care is not reducing complications from type 2 diabetes, such as amputations and kidney failure.

“The health system has made it the responsibility of the client with this simplistic idea that if you live healthy, eat healthy and exercise, you’re less likely to have type 2 diabetes. We know there’s more to it than that,” says Lorraine McLeod, associate director of the Diabetes Integration Project (DIP), a mobile program that First Nation leaders support to provide on-reserve diabetes care and treatment to more than a dozen First Nations communities in Manitoba.

Programs such as the centre’s DIP, B.C.’s Diabetes and My Nation and the cross-Canada FORGE AHEAD program have made significant improvements in diabetes prevention and management by being created by or developed in partnership with First Nations communities.

Since the late ’90s in Manitoba, First Nations leaders have been calling for action and collecting the necessary data to address the growing epidemic of diabetes in Indigenous communities.

“Oftentimes, research has been led by non-Indigenous researchers who have used their voice and academic lens to analyze Indigenous people, which often leads to continued stigmatization, and upholds the colonial practices and policies that were put in place to assimilate First Nations, Métis and Inuit people into Canadian society,” says Leona Star, the centre’s director of research.

As an example of a dataset that accurately identifies First Nations according to their own indicators of well-being, Star points to the national Regional Health Survey (RHS), which she says was “designed and delivered by First Nations with our cultural framework and code of ethics.”

According to Star, RHS data has led to federal funding for multiple Indigenous health initiatives, including diabetes prevention. While Star emphasizes the need for First Nations people to govern their own information and data, known as “data sovereignty,” she calls for more action.

“It is also important to look at the effectiveness and impacts of research findings,” says Star. “Although significant investments have been made to undertake research around diabetes, the rates of diabetes continue to increase and climb especially amongst First Nations.”

While evidence led or co-led by First Nations is available, she says what is lacking are policies and implementation recommendations to address discrimination and disparities in health care.

Wharton agrees and says the key question is why researchers and health care providers aren’t acting on what they already know.

To address the disparities created by bias, racism and systemic inequalities, he says it’s time that practitioners embrace the strengths of Indigenous peoples and people of colour, rather than assessing how these patients adhere to a system that wasn’t designed for or by them.

“We need to shake the foundations of how we help,” he says. •

Insulin: A Patient’s Point of View

Illustration by Jude Buffum

Whither the Cure?

By Jim Oldfield

“The pancreas,” says Professor Gary Lewis, an endocrinologist at Toronto General Hospital and director of the Banting & Best Diabetes Centre at the Temerty Faculty of Medicine, “is like an exquisitely sensitive and perfectly networked computer.”

Second by second, he notes, the pancreas secretes just the right amount of insulin or glucagon to lower or raise blood sugar — into the portal vein that leads directly to the liver, site of key metabolic processes — then distributes insulin to every tissue in the body via general circulation.

“Insulin injections are life-saving, but administered under the skin and nowhere near as precise,” says Lewis, who is also a scientist and professor of physiology and medicine at U of T. “It’s extraordinarily difficult to mimic the function of a healthy pancreas.”

That’s one reason a cure for diabetes has proven elusive almost 100 years after the discovery of insulin. Another big reason is the complexity of how the disease arises.

In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas, creating a life-threatening spike in blood sugar.

Type 2 diabetes usually comes on more slowly, as the body becomes resistant to insulin or the pancreas can’t produce enough of it.

Genetics play a role in both types. Exposure to viruses and other environmental effects may be a factor in type 1. Lifestyle factors, including weight gain and physical inactivity, are strongly linked to type 2.

The bottom line, says Lewis, is that diabetes is a multifactoral disease, and we’re not close to a cure.

Ask about treatments, though, and Lewis gets excited.

The last two decades have brought a plethora of clinical and research advances, from new drugs to boost and sensitize the body to insulin and promote weight loss, to lifestyle interventions that improve diet, continuous monitoring of blood sugar, long- and short-lasting insulin, better insulin pumps, pancreatic transplants, and preclinical stem cell and immunosuppressive therapies.

“Progress on treatments has been fantastic, especially for type 2,” Lewis says. “I’m very, very hopeful.”

The distinction between treatment and cure in medicine is often unclear. And for the 3.6 million Canadians living with diabetes, that distinction matters less and less, if the goal is a full and healthy life.

_Body Weight: We Know What to Do, But . . . 

Type 2 diabetes accounts for about 90 per cent of diabetes cases in Canada. Prevalence is rising, but Canadians with type 2 diabetes are living longer and have fewer diabetes-related complications.

“The clinic doesn’t look like it did 30 years ago,” says Lewis, who mainly treats patients with type 2. “We see fewer amputees, less blindness. Patients are generally healthier, and their prognosis is often excellent if they maintain their blood sugar target and other key parameters.”

Weight loss is a cornerstone of treatments to lower blood sugar, and recent research has strengthened the link between weight reduction and type 2 diabetes management. Some people with type 2 can lose weight and control blood sugar through dietary changes and exercise alone.

Bariatric surgery is very effective for weight loss and often results in diabetes remission, although it comes with surgical risks and is expensive.

“If we could prevent obesity, we could greatly reduce the incidence of type 2,” Lewis says. “And experiments have shown we can get a remission with lifestyle changes, so we know what works.”

The problem is broad implementation.

“I’ve tried to lose weight and I know how difficult it can be, especially in an environment of convenient and inexpensive calories,” Lewis says. Moreover, factors such as income, education, ethnicity, access to healthy food and living conditions can make lifestyle changes that curb obesity nearly impossible.

“Social determinants of health are overwhelmingly the most important influence on who gets type 2 diabetes, and how well or poorly they do with it,” Lewis says.

Fortunately, dozens of new drugs for diabetes have hit the market in the last two decades. 

Medications for weight loss round out the armamentarium, and some also protect against kidney damage and lower cardiac risk. Current therapies can reduce body weight up to 10 per cent, although a loss of 20 per cent or more would have a greater effect on outcomes for patients with type 2 diabetes, says Professor Jacqueline Beaudry, an assistant professor of nutritional sciences at the University of Toronto who studies links between obesity, hormones and diet.

Beaudry is probing the biology that underpins these medications, including the gut hormones GLP-1 and GIP. They control blood glucose and reduce appetite, but scientists are unsure how. “If we could understand their mechanisms of action, we could design better drugs,” Beaudry says.

_Loops and Leaps

Recent advances in treating type 1 diabetes have also been striking.

Dessi Zaharieva was diagnosed with type 1 diabetes at age seven and has lived with it for 24 years. She says advice and therapies are more individualized today and that technology has radically changed the patient experience.

“It’s a sign of progress that now patients on continuous glucose monitoring sometimes resent a daily fingerstick blood test,” says Zaharieva, a postdoctoral scholar in exercise physiology and blood glucose management at Stanford University.

“As a child I had to test my blood every hour or so, then contend with big dips and spikes in glucose,” she says. “Before that, patients had to urinate on a stick. It’s easy to forget how far we’ve come.”

Zaharieva switched from insulin injections to a pump technology when she was 13. The change gave her better control of the hypoglycemia she experienced after exercise and helped her compete in martial arts. She later represented Bulgaria and Canada in taekwondo. 

Today, Zaharieva uses a closed-loop system that some call an artificial pancreas. It includes the mobile app Loop, which takes blood sugar readings every five minutes, and based on an algorithm adjusts the insulin released by a pump. The system is connected by a device that translates radio signals to Bluetooth.

The system has improved her daily ‘time in range’ — how long she spends in the target glucose zone. It still requires user interaction, but future iterations may include automated inputs for carbohydrates such as photos of food, and motion sensors to detect exercise. A non-profit organization called Tidepool is now building an FDA-regulated version of Loop. 

_Whither the Future?

Cell therapy could prove more liberating still for people with type 1 diabetes. University labs and biotechs are working on implantable devices that house insulin-producing cells derived from stem cells.

To that end, Professor Cristina Nostro and her team in the McEwen Stem Cell Institute at University Health Network recently discovered a more efficient way to generate and purify pancreatic precursor cells from human stem cells in the lab.

They have also found a way to vascularize those cells by working with Professor Sara Vasconcelos, an assistant professor at U of T’s Institute of Biomedical Engineering. Together, they have extended the survival and functionality of the cells in animal models of diabetes.

The biggest problem with these therapies is that the immune system rejects them. The same challenge currently hinders pancreas and islet transplants. 

“The immune system is an amazing machine, we’re lucky it’s so good,” says Nostro, who is an associate professor of physiology at Temerty Medicine. “But it’s very difficult to control when it goes awry, as in autoimmune conditions.”

Nostro is working with immunologists at the university on a method to protect insulin-producing beta cells from immune rejection, and she says many researchers in the field are now focused on immune-protective approaches.

Another strategy for type 1 diabetes is to tamp down the autoimmune response before the disease progresses. The idea is to prevent immune cells that damage the pancreas while the body still produces beta cells.

“Groups around the world are bringing different ideas and creative approaches to treat type 1 diabetes, that’s the beauty of science,” says Nostro. “I am very hopeful about what the future holds. Who knows? Maybe we will see hybrid technologies combining a pump and cells. We have to keep an open mind.” •

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By John Lorinc

When Professor Ilana Halperin (MSc ’13, PGME ’13), an assistant professor at U of T’s Temerty Faculty of Medicine, sees new patients with diabetes, she makes it a practice to inquire about more than their health and lifestyle. 

“The first thing I do,” she says, “is ask people about their drug coverage.” 

Their answers affect what she prescribes. 

Appropriate doses of this life-sustaining treatment — insulin or related compounds, as well as the equipment to administer it and monitor the condition — can run to almost $5,000 a year (according to 2017 figures compiled by Diabetes Canada). It is a significant burden for those without private or employer-provided health insurance. 

Halperin, a Sunnybrook Health Sciences Centre endocrinologist, estimates that 10 to 20 per cent of her diabetes patients ration their insulin and testing supplies. 

She tweeted last year about a 26-year-old graduate student with type 1 diabetes who no longer qualified for OHIP’s drug coverage for young people, and had maxed out her university insurance for meds and supplies. 

The student was taking just enough insulin to keep her from going to the hospital with high blood sugar, but not enough to manage her diabetes as well as she could.

The cost of the recommended insulin doses was forcing the student to make untenable choices, like choosing between buying groceries, school supplies or insulin. 

Halperin’s concern when she encounters someone rationing insulin is that they are managing the disease in a “sub-optimal” way and are at considerable risk of long-term consequences, such as blindness or foot amputation. 

“There are too many people living in Canada who can’t afford these medications,” she says.

Today, with the incidence of diabetes rising rapidly, the cost of insulin treatment is a major public health and public policy question, and not just for Canadians. 

“Insulin is inaccessible to thousands of Americans because of its high cost,” an editorial in the New England Journal of Medicine noted last year. 

Halperin says that the pharmaceutical industry has developed several new “state of the art” varieties of insulin, as well as devices such as continuous glucose monitors that significantly reduce the risk of low blood glucose and make dosing far more precise. 

In other words, part of the price escalation over the past decade or so has to do with the intellectual property rights associated with the innovations. 

But the cost of insulin drugs is a complex, politically sensitive topic that goes well beyond intellectual property. 

The list price in the U.S. is about 10 times higher than in Canada, a differential that has given rise to “insulin caravans” that (until COVID-19) were coming across the border to purchase the medication here. 

“We have a lot of compassion and can absolutely understand the desperation people may feel,” says Seema Nagpal, vice-president of science and policy for Diabetes Canada. But she adds, “Canada can’t be the drugstore to the United States.”

The differential has everything to do with public policy. 

In Canada, the Patent Medical Review Board sets the maximum list price for a dose of insulin but doesn’t regulate the cost of related equipment. 

For those between 26 and 65 years old, the cost of the drug outside of a hospital setting is not covered by Ontario’s health plan. 

In the U.S., the price variability is far higher because there are multiple markets, says Professor William Mitchell, a professor of strategic management at the University of Toronto’s Rotman School of Management. 

These markets include the big publicly run health plans, employer-funded health insurance, pharmacy benefits managers, pharmacy retail giants and insurers operating in the markets established under the Affordable Care Act. 

The pricing system, according to a 2018 study by the American Diabetes Association (ADA), is “very complex.” 

“With this system, there is no one agreed-upon price for any insulin formulation,” reads says the study.

The study was based on the findings of an ADA working group established in 2017 to better understand the dynamics of insulin prices, which are subject to myriad factors such as rebates, discounts and the relative purchasing power of third-party payers. 

“A consistent observation made to the working group was the lack of transparency throughout the insulin supply chain,” the study concludes.

Mitchell, who is also the Anthony S. Fell Chair in New Technology and Commercialization, notes that Americans with full coverage may not pay anything at all if their employer-provided health plans provide no copayments.

“Roughly 80 per cent of the population are getting drugs for a relatively low price,” he says. 

But the millions of Americans who may not have a workplace plan and don’t qualify for Medicaid may be forced to pay the steep retail price. 

Mitchell adds that the equipment prices in the U.S. — for supplies such as glucose monitors and insulin pens — are lower because there’s more intensive competition in the retail sector.

In Canada, the maximum list price is much lower, and many people have access to drug coverage through private health plans. 

Those who fall between the cracks must rely on a mish-mash of supports, including compassionate access programs that drug companies provide, a federal disability tax credit, a Diabetes Canada program that covers the cost of blood glucose test strips and even, in a pinch, free samples from doctors’ offices. 

As a physician treating individuals with diabetes, part of Halperin’s work with vulnerable patients is helping them access compassionate samples from pharmaceutical companies, rebates on testing supplies and tax credits. 

But Nagpal points out that the crisis posed by the one-two punch of high prices and increased prevalence can’t just be seen in terms of costs. 

“We need to collectively work together to implement policies and programs that address such things as the built environment that will promote active lifestyles, improve the food environment and monitor the health outcomes,” she says. “We live in a society that promotes disease.”

The eve of the centennial of arguably Canada’s most-important drug discovery seems like a fortuitous moment to have that conversation. 

“Frederick Banting and Charles Best gave life to so many people with diabetes,” says Nagpal. “It is now 2021, and we have an opportunity to reflect on how far we’ve come and how far we have to go.” •

Illustration by Anson Chan

Despite investments in diabetes care, a growing number of people with diabetes are experiencing amputations of their lower extremities. 

This increase in amputations is partly because of organizational challenges in Canada’s health care systems. Our systems are focused on tackling huge issues related to diabetes, such as controlling blood sugars and treating heart disease.

But in terms of holistic care that addresses the needs of people with diabetes — such as access to foot care and specialized shoes to prevent amputations — we are failing. 

Limb preservation centres, like those in the U.S. and Europe, could help people with diabetes manage foot infections and ulcers, which heal poorly and don’t respond well to pharmaco-therapy. These centres could also assess the risk of future complications for patients, and reduce the number of amputations. 

This lack of specialized services impacts all patients with diabetes. Black, Latino and Indigenous populations across North America are disproportionately affected by lower-extremity amputations from diabetes complications.

We must develop more equitable strategies to reduce amputations for all of our patients.

I’ve worked at the University of Toronto’s Temerty Faculty of Medicine for 38 years. Today, I lead a lab that looks at how regulatory peptides in the intestine, pancreas and brain affect our overall health. 

For the entire time I’ve been at U of T, I have also, personally, been managing type 1 diabetes. 

I’ve always seen myself as a person with diabetes, not a type 1 diabetic. I don’t let it define me, but it certainly motivates me. The diagnosis was the original impetus for my career. You control the disease, not the other way around.

I identified that I had type 1 diabetes in 1979. I was 21 years old, doing a PhD at McGill University and showing all of the classic symptoms of the disease. At one point, I was losing one pound of weight per day. 

After my diagnosis, I learned how to manage the symptoms I was experiencing. And in 1982, I came to U of T to do a postdoctoral fellowship with Professor Mladen Vranic  (Hon DSC ’11) on extra-pancreatic glucagon. 

My research has primarily looked at intestinal proglucagon-derived peptides such as glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). 

My work with GLP-1 has been applied to people with type 2 diabetes and obesity, and has developed new models to show how GLP-1 is naturally produced in the body. 

Most recently, I am examining circadian patterns of GLP-1 secretion, which could affect how people with uneven sleep routines might be at higher risk of developing diabetes. 

Overall, I feel very fortunate. When I was first diagnosed, the average lifespan for someone with diabetes was 48 years. But I always ignored that statistic.

Things have really changed — there has been incredible progress in the treatment of diabetes and the prevention of complications. It has enabled people with diabetes to lead full, healthy lives. 

I’ve climbed Kilimanjaro, and I’ve had a great career in science. You follow where both life and the research take you.

When I was a fellow in pediatric endocrinology at the University of Pittsburgh in the late 1970s, I was treating a patient with type 1 diabetes who showed signs of an eating disorder. 

However, the psychiatrists wouldn’t diagnose her with an eating disorder because she didn’t have the usual expressions of anorexia nervosa, such as limiting how much food she ate.  

Years later, I became a faculty member at the University of Toronto and met Professor Gary Rodin, a psychiatrist specializing in eating disorders. We had both noted eating disorders among teenagers and young women with type 1 diabetes. These patients frequently restricted their insulin, or stopped taking their insulin, to lose weight. 

In 1982, we started studying this behaviour and found that adolescent females with type 1 diabetes were up to two times more likely to have an eating disorder than their non-diabetic peers.

This research helped us better understand how this disorder impacts diabetes patients and how to treat them. 

In the short term, the disorder leads to poor glucose control. Insulin omission can cause the body to break down fat too quickly and leads to the life-threatening condition diabetic ketoacidosis.

In the longer term, the disorder can lead to the early onset of eye and kidney damage. 

Managing diabetes is a complicated process — made even more complicated with an underlying eating disorder. Shining a light on this under-researched area has helped to ensure that these patients are not obscured. 

We know diabetes education programs help people manage the disease. So why is it a challenge to keep program participants tracking their exercise, keeping a food journal and using other management strategies? 

Studies have found that participant dropout rates from diabetes education programs range from more than 20 per cent after three months, to more than 60 per cent at nine months. 

Can you imagine what would happen if about 60 per cent of people with another disease said, ‘I’m not going to take my medication’?

As part of my PhD studies, my peers and I designed a research protocol to better understand what’s behind the dropout rates. The project attracted two occupational therapy students.

What we found is that individual factors, such as how accepting a person is of their diabetes diagnosis, and logistical challenges, such as not having transportation to and from the classes, can impact attendance. Social factors, such as making friends in class or feeling connected to the educator, can also influence attendance.

A mix of speakers from different health care specialties — physicians, dieticians, pharmacists and occupational therapists — and goal setting also help people keep going.

Conversations about racism and sexism are often masked in health care settings in Canada.

That’s why I interviewed 28 patients with type 1 and type 2 diabetes.

I wanted to find out how a patient’s perceptions of their health care provider’s age, gender and ethnicity impacted their relationship with the professional. The results were published this past June in the Canadian Journal of Diabetes.

So, what did we find out?

Representation mattered to patients. One 61-year-old Black woman told me that she placed her diabetes care on the back burner because she felt that no one shared in her struggle, her pain and her challenges with diabetes.

“I had nobody to represent me,” she said.

Through the research, we also learned that patients had vastly different expectations of male and female health care providers – women were expected to be more caring and offer more support than men doing the same job.

Patients also expressed racist views to me.

Anecdotally, we hear racialized health care providers talk about experiencing difficulties when interacting with patients. When we get to that underlying reason why, it truly is racism.

A lot of people seem to look at racialized health care providers as less accomplished or less capable. That is wrong.

Ultimately, the takeaway is that we need to lend more support to racialized health providers who are helping patients with diabetes.

The providers are experiencing micro-aggressions while they’re providing care, and there should be a way to recognize and bolster their accomplishments.

We need to provide avenues of support.

By Haley Lewis

Professor Satya Dash (PGME ’13) has heard the stereotypes many times: Type 2 diabetes is due solely to poor diet and lack of exercise. Or: With stronger willpower, patients will lose weight and their diabetes will improve. 

But for Dash, understanding diabetes means looking beyond a person’s behaviour and habits.

His work centres the disease on genetics, and is disrupting public stereotypes and assumptions around how people develop type 2 diabetes. 

“In the general population, most people will become insulin resistant as a result of weight gain, but the threshold at which it happens will vary from person to person,” he says. “And that threshold is, to a large extent, determined genetically.” 

Dash’s research focuses on finding the genetic factors that make people prone to obesity and insulin resistance, which then affect their likelihood of developing type 2 or high blood glucose levels.

“There can be different conditions that lead to high blood glucose, such as if a person is insulin resistant, if they don’t make enough insulin or a combination of the two,” he explains. 

Dash completed his clinical training and a PhD in the genetics of insulin resistance at the University of Cambridge.

In 2011, he came to the University of Toronto to join the Banting & Best Diabetes Centre and complete a four-year postdoctoral fellowship in Professor Gary Lewis’ lab.

Dash pursued this fellowship because he was interested in learning more about how the gut produces fat, a complex process regulated by diet and various hormones, and in better understanding metabolic disease. 

It’s a theme that has persisted in Dash’s work.

“Today, I’m still working to try to use genetics to better understand the different ways in which one can develop type 2 diabetes with weight gain, and whether this impacts how a patient responds to treatment,” he says. “This is important because it can potentially lead to more individualized treatment plans for patients.”

Part of tackling the public health crisis posed by the accelerating number of Canadians with type 2 is investigating the cause of the increase.

“There are definitely social components to whether someone develops type 2 diabetes. Our genes have not changed,” he says. 

“The major challenge facing researchers like me is to try and understand what exactly predisposes people to develop type 2 diabetes. And then our job is to discern what the best treatment is.”

Part of the solution might mean suggesting that more patients explore bariatric surgery.

“Bariatric surgery is the most effective treatment for sustained weight loss, and it can actually cure type 2 diabetes in many people,” he says. “But if you look at the number of people in Canada who can potentially access bariatric surgery versus the number who actually have the procedure, there’s a large discrepancy.”

Dash notes that there is research indicating that there’s a stigma about people who choose to lose weight through bariatric surgery.

“It’s thought of as taking the easy way out,” he says. “That attitude contributes to people not having surgery. We need more progressive attitudes and a change in our approach.” •

Satya Dash is an assistant professor with the Temerty Faculty of Medicine’s Department of Medicine and a staff physician in the division of endocrinology at Toronto General Hospital. He is also the medical director of the bariatric program at University Health Network.

By Emily Kulin

If all had gone according to plan in 1984, Professor Daniel Drucker’s remarkable research career likely would have turned out much differently.  

“After completing my residency, I went to Boston to work in a lab investigating thyroid gland actions — my main interest at the time. But just as I arrived, the thyroid project started to wind down,” says Drucker (MD ’80, PGME ’84), an endocrinologist at Sinai Health’s Lunenfeld-Tanenbaum Research Institute and a professor at University of Toronto’s Temerty Faculty of Medicine.

“I was asked to switch to the lab’s new project looking at glucagon, a peptide hormone produced by the pancreas that helps regulate blood sugar. I was so disappointed but went along with it.” 

Disappointment soon transformed into a newfound passion and, eventually, groundbreaking discoveries about glucose-regulating hormones and their impact on how our bodies process nutrients and absorb energy. 

“Looking back, it kick-started my interest in this area,” says Drucker. “I was in the right place at the right time.”

Drucker’s work on GLP-1, a glucagon-like peptide, has been especially important for people with type 2 diabetes and obesity. 

“GLP-1 has a large number of actions,” he explains. “It acts on the pancreas to make more insulin, helping your body regulate blood sugar. It also makes you feel full and less hungry, reducing appetite.”

Today, Drucker holds more than 30 U.S. patents, and his work has contributed to the development of several drugs that have transformed how diabetes and obesity are treated. 

“Diabetes and obesity are two very common diseases that are interrelated,” Drucker says. 

“Due to my work, I’m always meeting people who are taking medications that were developed based, in part, on my research. Seeing my basic science find a useful application is just so cool. It’s a scenario many scientists aspire to but, in reality, it’s actually very challenging to make this kind of direct translation. I’m very fortunate.”

Drucker recently established the Drucker Family Innovation Fund with a $2 million commitment to the Temerty Faculty of Medicine and University Health Network, reflecting where much of his early discovery work was done. 

The endowment will support early-career research scientists in Toronto, and fund new biomedical research on diabetes and metabolism. 

Drucker’s gift was matched by both U of T and the University Health Network, bringing the fund’s total value to $6 million. The endowed fund will support researchers for generations to come.

“Throughout my career, I’ve licensed my intellectual property to a number of pharmaceutical companies who have then provided revenue back to me, as well as back to U of T and the hospital,” he says. “I found myself thinking, ‘Wouldn’t it be wonderful if each of us directed a portion of these revenues so that other scientists working on innovative discovery projects could benefit?’”

The University of Toronto’s Banting & Best Diabetes Centre and Department of Medicine will administer the fund. It will make its inaugural grants in 2021 to align with the 100th anniversary of the discovery of insulin.

Also in 2021, there will be the virtual “Insulin100” scientific symposium that the University of Toronto is hosting and Drucker is chairing. The symposium will bring together the world’s leading experts on diabetes. 

“Scientific advances related to diabetes have been transformative over the last century,” says Drucker.

“Medicine used to be a very primitive art. Even 100 years ago, we had no real understanding of disease. Insulin is often described as the first real drug to treat a disease in a targeted manner. Now, 100 years later, we’re continuing to make rapid progress and we have so much potential to make new breakthroughs. I’m hopeful the Drucker Family Innovation Fund can help contribute to these advances.” •

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This package of insulin vials was prepared in 1924 in the Connaught Laboratories on the University of Toronto campus.

The labs were run by Dr. John FitzGerald, whose office at the University of Toronto Medical Building was two floors beneath the space where Dr. Frederick Banting and Dr. Charles Best discovered insulin in 1921.

By 1923, the Connaught Laboratories were producing 250,000 units of insulin per week.

Source: Connaught Laboratories & The Making of Insulin
Image: Sanofi Pasteur Canada (Connaught Campus) Archives

Join us in celebrating the 100th anniversary of the discovery of insulin, visit insulin100.utoronto.ca.