Brianne Tulk

'A Swiss Army knife': Daniel Drucker bets the gut hormone GLP-1 can be used to treat far more than diabetes

Christopher.Sorensen — Wed, 03 Nov 2021 14:28:07 +0000

'A Swiss Army knife': Daniel Drucker bets the gut hormone GLP-1 can be used to treat far more than diabetes

Christopher.Sorensen Wed, 11/03/2021 - 10:28

Cutline

A pioneer of gut hormone research that led to therapies for type 2 diabetes, obesity and short bowel syndrome, Daniel Drucker is investigating whether the same hormones can help treat everything from heart disease to Alzheimer's (photo by Johnny Guatto)

Brianne Tulk

Topic

Our Community

Insulin 100

Temerty Faculty of Medicine

Diabetes

Mount Sinai Hospital

Research & Innovation

Research & Innovation. Faculty of Arts & Science

Daniel Drucker is unraveling a medical mystery.

Drucker, a professor in the department of medicine at the �ؿ�ζSM’s Temerty Faculty of Medicine and a senior scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, has pioneered research on gut hormones that has led to life-changing therapies for people with type 2 diabetes, obesity and short bowel syndrome.

Now, Drucker’s lab is studying how these same hormones work in the context of other conditions throughout the body, which could result in treatments for an even wider variety of diseases.

Drucker, an inductee to the Canadian Medical Hall of Fame and winner of the Canada Gairdner International Award, is most well-known for his contributions to the discovery of glucagon-like peptides (GLP-1 and GLP-2), gut hormones that help control insulin and balance blood sugar levels, and for the development of related therapies for diabetes, obesity and intestinal failure.

Yet, beyond conventional metabolism, drugs based on GLP-1 can also reduce plaque formation in arteries, or atherosclerosis, and control inflammation in several organs. Plaque and inflammation are linked to heart attack, stroke and other cardiovascular diseases – some of the leading causes of death in people with type 2 diabetes and obesity.

The drugs also show promise for treating liver disease and Alzheimer’s disease.

In a study recently published in JCI Insight, Drucker’s research team investigated the role that specific GLP-1 receptors play to make GLP-1 drugs effective against cardiovascular and liver disease in the aorta and liver of mice.

In the first half of the study, Drucker’s team saw that the GLP-1 drug reduced plaque in the arteries, but the presence or lack of the GLP-1 receptor in blood vessel and immune cells in the aorta did not play a role.

“We’ve ruled out the importance of receptors in these cell types, but we still don’t fully understand how GLP-1 reduces atherosclerosis," says Drucker.

This negative result was valuable, but the second story the paper told was more novel.

The mice developed fatty liver disease, liver fibrosis and liver inflammation through the same high-fat diet that triggered plaque development in their arteries. The researchers saw that the mice with GLP-1 receptors in specific cells in their livers responded well to the GLP-1 drugs, whereas the “knockout” mice without the GLP-1 receptor in these cells did not – despite both groups losing weight as an effect of the GLP-1 drug.

This outcome suggests that even though weight loss has conventionally been important for GLP-1 action to reduce fat and inflammation in the liver, it may not be the whole story. In, fact GLP-1 may reduce liver inflammation through mechanisms independent of weight loss.

“This paper is the first to show that even though weight loss is the same in both groups of animals that we studied, the animals that were missing the GLP-1 receptor in the immune cells in the liver did not have the same therapeutic benefit,” Drucker says. “It's really the first paper to show that there's another element to the story of how GLP-1 works in the liver.”

GLP-1 drugs are already in phase three trials to treat liver diseases such as non-alcoholic steatohepatitis, a more aggressive form of fatty liver disease. So, it was not surprising for the researchers to see that mice treated with GLP-1 drugs saw reduced liver inflammation.

But Drucker said it was exciting to identify GLP-1 receptors in specific immune cells in the liver, which may be necessary to get the full therapeutic effects of GLP-1 drugs to treat fatty liver and liver inflammation. This finding could lead to more targeted and effective treatment options.

Overall, the study is another piece in the puzzle of how GLP-1 works in different areas of the body. But researchers still need a better understanding of how GLP-1 drugs produce their multiple therapeutic benefits in treating diseases.

“If I could figure out how GLP-1 reduces heart attacks and strokes, and I knew where that magic was happening, maybe we could make even better, more targeted GLP-1 therapies to produce more effective medicines,” Drucker says.

Drucker credits his background as a clinician scientist for bringing the perspective of patients and their unmet medical needs into his research. Although he hasn’t been directly involved in patient care for 12 years, he calls his training as a physician and a clinician scientist the “secret sauce” to his research.

“What clinician scientists are really good at is asking the important questions that are directly relevant to human disease,” he says. “I’ve always tried to ask questions that are not just interesting for the sake of basic science, which is important by itself, but also questions that might inform how disease pathophysiology and drugs work clinically.”

He says that what makes the GLP-1 story so exciting is that physicians are able to treat diabetes and obesity by conventionally lowering blood sugar or bodyweight, but also by attacking cardiovascular risk, the number-one cause of death these patients face.

“Until recently, there haven't been therapies that go beyond lowering blood sugar or reducing bodyweight to actually show there's a reduction in death,” Drucker says. “GLP-1 therapies are changing the natural history of these diseases.”

Improved disease outcomes may soon extend to other conditions. Emerging data suggest that GLP-1 drugs have an anti-inflammatory effect to treat a wide variety of diseases, and the next frontier could be Alzheimer’s disease now that GLP-1 drugs targeting the condition recently entered phase three trials.

Drucker says that if GLP-1 drugs work to treat Alzheimer’s, it would likely reflect a combination of neuroprotection, improved brain metabolism and reduction of inflammation associated with the condition, which could also improve cognition and slow the course of disease.

“Whether it’s in the pancreas, blood vessels, the liver, or the brain, increased inflammation is a driving component of the pathology of all kinds of different diseases,” he says. “I believe that one reason GLP-1 is the Swiss Army knife of metabolism – that it can do so many different things in so many different organs – is its ability to reduce inflammation.”

Exactly how that happens, however, is still shrouded in mystery, Drucker says.

“There’s a huge amount of uncertainty as to how GLP-1 controls inflammation in different organs in the body, and that’s a major focus for our lab right now.”

U of T's Andreas Laupacis takes the helm at the Canadian Medical Association Journal

davidlee1 — Mon, 07 Oct 2019 04:00:00 +0000

U of T's Andreas Laupacis takes the helm at the Canadian Medical Association Journal

davidlee1 Mon, 10/07/2019 - 00:00

Cutline

"Taking on a new job is always exhilarating and slightly scary," says Dr. Andreas Laupacis of his new CMAJ role "But I'm going to something that I'm looking forward to” (photo courtesy of Dr. Andreas Laupacis)

Brianne Tulk

Topic

Our Community

Dalla Lana School of Public Health

Faculty & Staff

Faculty of Medicine

The �ؿ�ζSM's Dr. Andreas Laupacis takes over this week as editor-in-chief of the Canadian Medical Association Journal (CMAJ), the peer-reviewed academic journal published by the Canadian Medical Association.

Laupacis, a professor in the department of medicine and the Dalla Lana School of Public Health, is also a general internist and palliative care physician at St. Michael’s Hospital and scientist at the Li Ka Shing Knowledge Institute. He is stepping away from his clinical and academic duties for the new role, which came after a lengthy international search as the journal positions itself to broaden its impact in health policy and further promote medical knowledge.

“The CMAJ has a very storied tradition and it’s had a lot of influence over the years,” Laupacis says. “It's a journal where research that's of relevance to Canadian physicians and people that are managing the Canadian health-care system is published.”

Beginning his medical career at a time when the evidence-based medicine movement was only starting to become popular among physicians, Laupacis says the CMAJ had a meaningful impact on his own research and practice. A series that the journal published called “Critical Appraisal” influenced how Laupacis approached research and medicine as early as when he was a medical student.

“It talked about how to read the medical literature and apply the findings to your practice,” he says. “That was hugely influential to me.”

For more than 30 years, Laupacis has spent his career at the forefront of research that broadly spanned clinical epidemiology, health services research, health policy and, most recently, patient involvement. Until 2018, he was executive director of the Li Ka Shing Knowledge Institute, stepping down around the same time that he was tasked with the role of patient involvement lead for the department of medicine.

A passionate champion for enhancing the voice of patients within the health-care system, he has advocated for including patients on committees and in broader decision-making.

“Fundamentally, patients are the ones who are ill and who are seeking help from the health-care system,” Laupacis explains. “They understand their lived experience and their experience with the health-care system in a different way than researchers or clinicians.”

Although it’s too early to describe concrete plans, Laupacis can see where there could be opportunities to enhance patient and public involvement in the CMAJ. Whether that’s involving patients on committees or finding a mechanism for patients to communicate with him as editor-in-chief, he’s eager to include patients as a complementary voice to physician and academic contributors.

“We're in the era where I would like to see some of the material published in the CMAJ be influenced and read by Canadian public and patients,” he adds.

Laupacis describes himself as having a passion for writing, and being an editor is familiar territory. In 2011 he launched Healthy Debate, a website that uniquely integrates diverse voices into the conversation about health care in Canada, followed by Faces of Health Care in 2015. As Laupacis steps down to take over at the CMAJ, Dr. Seema Marwaha, an assistant professor in the department of medicine and general internist at St. Michael’s Hospital, will be Healthy Debate’s new editor-in-chief.

Although taking the lead at the CMAJ is coupled with a departure from clinical practice, Laupacis says that for this stage of his career, the timing and the fit is right.

“Getting called at four in the morning just seems a little more painful than it did before.”

As he reflects on the many roles he’s stepping away from across U of T and St. Michael’s Hospital, he says he hopes he’s instilled an enthusiasm for research and clinical care among those he has mentored and taught. And, he adds, “a recognition among them of how privileged we are to be physicians.”

“It feels like a big change,” Laupacis says. “I'm moving away from an everyday relationship with U of T. Taking on a new job is always exhilarating and slightly scary. But, I'm going to something that I'm looking forward to.”

Risk of suicide twice as high among those who sustained concussion: U of T-led study

noreen.rasbach — Mon, 19 Nov 2018 15:25:08 +0000

Risk of suicide twice as high among those who sustained concussion: U of T-led study

noreen.rasbach Mon, 11/19/2018 - 10:25

Cutline

“It is important to note that the vast majority of people who have a concussion do not experience a suicide-related outcome, and I do hope that is reassuring to people,” says Dr. Michael Fralick (photo by Ben Hershey via Unsplash)

Topic

Research & Innovation

A new study by researchers at the �ؿ�ζSM and other universities is highlighting the association between concussions and the risk of suicide. The study, published in JAMA Neurology, found that the risk of suicide is twice as high for people who had at least one concussion compared to those who had not.

Dr. Michael Fralick, a general internist and trainee in the department of medicine’s Eliot Phillipson Clinician Scientist Training Program, led the research team that conducted a systematic review and meta-analysis of several other studies that explored the association between suicide and concussion. They found there was a heightened risk of both suicide and suicidal ideation following a concussion or other forms of mild traumatic brain injury (TBI).

Growing up playing contact sports like hockey, soccer and rugby, Fralick saw many of his friends sustain concussions. He also observed mounting reports of athletes who died by suicide following concussions and brain injury. Skeptical at first of the association between concussion and suicide, Fralick and his team decided to study the topic.

The research team – including researchers from University of Saskatchewan, University of California, San Diego, Harvard University and Ohio State University – reviewed data from 17 studies for more than 700,000 people diagnosed with concussion or mild TBI. Most of the studies included did not differentiate between the number of concussions an individual sustained and their respective rate of suicide risk.

“There were a few studies that included the number of concussions, and they suggested that multiple concussions were associated with an even higher rate of suicide-related outcomes,” says Fralick (pictured left).

Fralick emphasizes that although people who have experienced a concussion are at a heightened risk of suicide and suicidal ideation, the reported rate of death by suicide was extremely low at less than one per cent.

“It is important to note that the vast majority of people who have a concussion do not experience a suicide-related outcome, and I do hope that is reassuring to people,” he says.

The study contributes to a body of research that explores the outcomes and side-effects of concussions and TBIs. Noting that concussions are both common and frequently preventable, Fralick says more research is needed to address the risk of suicide following concussions and to identify strategies to reduce this risk.

“The burden of preventing concussions needs to be shared with policy-makers and professional organizations,” says Fralick. “It is encouraging to see athletic organizations have raised the age for some contact sports and implemented concussion policies to ensure athletes are removed from play if they have a suspected concussion.”

Individuals who have sustained a concussion and are experiencing anxiety and depression are urged to seek medical attention.

For those who play contact sports, Fralick adds: “Wearing a helmet and using a mouthguard can help reduce the risk of concussion. If someone has a concussion, it’s really important to rest, stay hydrated, and avoid alcohol.”

'What type of physician do I want to be?': U of T researcher on bringing a social justice lens to her clinical work

Christopher.Sorensen — Fri, 13 Jul 2018 17:37:35 +0000

'What type of physician do I want to be?': U of T researcher on bringing a social justice lens to her clinical work

Christopher.Sorensen Fri, 07/13/2018 - 13:37

Cutline

Dr. Adrienne Chan, an infectious disease specialist, has treated patients during some of the biggest epidemics in recent history, including the 2003 SARS outbreak in Toronto (photo by Ian Brown)

Brianne Tulk

Topic

Global Lens

Institute of Health Policy Management and Evaluation

Dalla Lana School of Public Health

Faculty of Medicine

HIV

Sunnybrook Hospital

University Health Network

Dr. Adrienne Chan has made a difference to lives around the world. An infectious disease specialist, Chan treated some of Toronto’s first SARS patients during the 2003 outbreak when she was a third-year resident. Since then, she has established public health programs in southern Africa and helped get 13,000 patients in Malawi on antiretroviral therapy for HIV. In 2014, she worked with the World Health Organization to provide care to Ebola patients and survivors in Sierra Leone.

Today she is an assistant professor in the Department of Medicine, staff physician at Sunnybrook Health Sciences Centre and the recipient of the department of medicine’s inaugural award for humanism in medicine. The award recognizes a faculty member who exemplifies a deep and abiding commitment to humanism in health care. Humanism is understood to be an acknowledgment of other human beings as individuals with autonomy, unique backgrounds, values and perspectives, and a commitment to address issues of inclusion, equity and social justice.

Chan sat down with U of T's Brianne Tulk to talk about how being on the front lines of major outbreaks solidified her commitment to equity and social justice, and how it has informed what humanism in medicine means to her.

You’ve been present for some of the biggest epidemics in recent history. Working with patients affected by SARS, Ebola and AIDS, what has this taught you about patient care?

It taught me how interconnected we are globally and that my role as a physician has to extend beyond patient care, keeping that global framework in mind. All kinds of complex and interconnected social, economic and environmental risk factors contribute to the emergence and spread of disease, and I think we have to actively engage in addressing those factors as part of the care we provide for patients.

Those experiences were particularly eye-opening for me with respect to the extremely negative effects of fear, denial and complacency, as well as the impacts of stigma and resource inequity on patient outcomes. You can’t have those experiences and not think deeply about the intersection of health and human rights. In particular, contrasting patient care in the settings where I worked in Africa with those in Canada has taught me the importance of bringing a social justice lens to my clinical work.

You were very early in your career when you treated some of the first patients in the SARS outbreak in 2003. What effect did this have on you?

It had a profound effect on me – to the point where I didn’t really talk about it that much for several years afterwards because I was still trying to process what happened.

At the time, I think the serendipity of being on call on the wrong day, at the wrong time, afforded me a unique opportunity that most post-graduate trainees would not have: to actively participate in the health system outside of pure clinical care. Working at the outset of the outbreak in Toronto meant that I was exposed, for the first time, to how organizations make decisions in real time to unique situations, how the public health system interfaces with the clinical care system, and also exposed me to aspects of program management, field epidemiology and outward facing public communication. It was kind of a baptism by fire on how to put out fires, when no one is totally sure about what’s causing the fire.

Reflecting in hindsight, it also taught me a lot about the kind of physician I wanted to be, by seeing the unexpected and human ways that both my peers and more senior health-care providers responded. It was probably the first time where I really asked myself: What type of physician do I want to be when an extraordinary circumstance happens? What does being a physician mean to me? How do I manage the effects of decisions that I make when the outcomes of those decisions affect more than just an individual but may affect the community? And how does the answer to all of these questions impact on the people I care about in my personal life?

What does humanism in medicine mean to you?

It’s funny because I was just reading an article in the Guardian on design where the designer said that a humanist approach to design takes an “inside-out approach and puts the person at the heart of the space.” I think that is a lovely way to also conceptualize humanism in medicine. We are trained to look at patients from the outside in, starting with “inspection” first and then moving by layers inward to make a diagnosis and come up with a treatment plan, using a complex system of pattern recognition. A humanist approach reminds us that, as front-line care providers. we should start instead by considering what well-being or health means to each patient individually and what they value, and consequently to respect that in our recommendations and services.

How would you describe your approach to person-centred care?

I always ask myself – and tell my patients this is what I am thinking – when faced with a clinical decision: Knowing what I know, what would I want to be done for myself or someone I care about?

I have to say that having the time to think about these questions makes me realize that I probably need to be the first person to try harder to take an inside-out approach. I think we all know this intuitively and aspire to practice this way, but in the reality of the busy day-to-day controlled chaos of clinical practice, it is often the first thing we lose sight of because of the mental demands of real-time clinical decision making and also the hectic nature of operationalizing patient care.

What inspired you to pursue a career in infectious diseases?

Definitely some of the patients that I interacted with during my formative years with infectious disease-related clinical issues made a deep impression on me. My experiences with the HIV epidemic just prior to the advent of combination antiretroviral therapy, and the subsequent impact of the introduction of highly active antiretroviral therapy, which happened in my first year of medical school, probably was also an influence. I think also having great clinical teachers in the city-wide infectious diseases division and interesting and meaningful clinical experiences helped consolidate my career choices.

What do you find most rewarding about your work?

Like everyone who provides health care, it’s having the opportunity to interact with people at what can be the most challenging times in their lives, and to try to have a positive impact. It’s certainly a privilege to have that opportunity, and I think it’s something I always remind myself on days where I am feeling a bit frustrated, harried, or stressed out – that the role we have in people’s lives is a privilege, and to always remember that.

I also love that my job has allowed me to meet with and work with incredible people – not just in Toronto, but all over the world. Whether it’s the nurses who have worked in the Anita Rachlis clinic at Sunnybrook since the beginning of the HIV epidemic, who were treating HIV patients at the beginning of the epidemic when other health-care workers were afraid to care for them, or the remarkable people who responded to SARS in Toronto or Ebola in West Africa, or the amazing team at Dignitas International and the Malawi Ministry of Health who I have worked with for over a decade in Malawi to build a strong national HIV program. I think I have been lucky to have been surrounded by such amazing people, many of whom are close friends as well as colleagues. I really feel fortunate to have colleagues whose compassion, intelligence, and work ethic inspires me to do better every day.