Dr. Bernard Zinman, C.M., and Dr. Daniel Drucker have been colleagues at the LTRI since 2006, where they are part of a diabetes research team that is among the most influential in the world.
But they have been friends for much longer — more than three decades, since meeting at the University of Toronto when Dr. Zinman was a young faculty member and mentor to Dr. Drucker, a resident in the division of endocrinology and metabolism.
“We’ve been friends all along,” says Dr. Zinman, Director of the Leadership Sinai Centre for Diabetes and the Sam and Judy Pencer and Family Chair in Diabetes Research, “but what brought us together scientifically is the magnitude of the problem of diabetes and the common purpose to improve the lives of diabetic patients.”
Both Drs. Zinman and Drucker are physician-researchers who strongly believe that having “one foot in both spheres” amplifies our ability to help the patients of today and tomorrow.
“Understanding the biology can lead to insights that can have a huge impact on care,” says Dr. Zinman. Likewise, the daily interaction with patients can shed light on how the disease affects people that bench research alone might not reveal.
“As a physician, you have one eye on the patient and you’re asking, ‘What are the real problems that patients with this disease face?’ As a scientist, you’re thinking, ‘How do I go about tackling the major unresolved questions about this disease?’” adds Dr. Drucker, Canada’s most decorated type 2 diabetes researcher.
Conquering type 1 and type 2 diabetes
Dr. Zinman’s work has concentrated on advancing the understanding and treatment of type 1 diabetes, a disease in which the body destroys the beta cells in the pancreas that make insulin. For more than three decades, he has played a key role in transforming the standard of care for type 1 diabetes as part of the leadership of the multi-centred Diabetes Control and Complication Trial (DCCT), the largest and most comprehensive study of its kind ever conducted and one of the most highly cited type 1 diabetes studies in the world. The study demonstrated that intensive diabetes control with insulin pumps or multiple daily insulin injections dramatically reduces the devastating, chronic complications of diabetes, such as visual impairment, kidney failure, nerve damage and cardiovascular disease.
Earlier this year, Dr. Zinman and his colleagues published a new paper related to the DCCT trial, reporting astonishing results: Those patients who received intensive insulin control treatment are now living longer, on par with peers without diabetes — an outcome unimaginable when the trial began in 1983.
Despite these major advances, the goal of duplicating the insulin naturally produced by the body, which has the ability to systematically regulate insulin levels for meals and exercise, continues to elude researchers.
“We’ve developed new insulin therapies with better characteristics and better methods for administering them, but duplicating physiologic insulin replacement has been an amazingly difficult task,” says Dr. Zinman.
“We still don’t understand why beta cells are destroyed,” explains Dr. Drucker, whose research has helped launch new, more effective drug therapies for type 2 diabetes, a complex disease that often presents with a wide range of contributing factors from insulin deficiency and insulin resistance, to inflammation, to obesity.
“Some people who develop diabetes exercise, are thin, eat healthy foods, but their beta cells don’t produce enough insulin,” says Dr. Drucker. “Other people smoke or drink, are overweight and have insulin resistance yet they don’t get diabetes. We still don’t understand all the factors that go into causing the disease in susceptible individuals,” says Dr. Drucker.
In its initial stages, type 2 diabetes is easier to manage, but as the disease progresses the beta cells’ ability to produce insulin diminishes and glucose levels may be more difficult to control, ultimately increasing the patient’s risk of developing complications, such as blindness and kidney failure. The disease is widely recognized as an epidemic, particularly as it increasingly occurs in younger people, creating a greater demand for therapies that improve treatment options while reducing the risk of complications and medication side effects.
Dr. Drucker’s lab has contributed to the development of two new classes of drugs, glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors. These drugs mimic the action of hormones called incretins (a family of gut hormones that increase insulin to control blood glucose) without causing weight gain or hypoglycemia, common side effects of traditional diabetes treatments.
His contributions have revolutionized treatment for millions of patients living with type 2 diabetes, earning him the honour of election to the Royal Society, the world’s oldest scientific academy, as well as the distinction of being only the second researcher to ever receive all three major international diabetes awards — the Manpei Suzuki International Prize from Japan, the Banting Medal for Scientific Achievement from the American Diabetes Association (described by some as the Nobel Prize for diabetes research), and the Claude Bernard Medal from the European Association for the Study of Diabetes.
Dr. Zinman and his colleague Dr. Ravi Retnakaran have also launched a new series of studies — the most recent of which, PREVAIL, is currently recruiting patients — that are designed to determine if therapies can be developed to specifically target deteriorating beta cell function in type 2 diabetes. These studies may ultimately change the paradigm for managing the disease.
“Can we put type 2 diabetes in remission? And can we then maintain that remission by newer therapeutic approaches?” asks Dr. Zinman. “That’s what we want to know.”
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