“The pancreas,” says Gary LewisThe endocrinologist at Toronto General Hospital and director of the Banting & Best Diabetes Center at the Temerty Faculty of Medicine at the University of Toronto is “like an extremely sensitive and perfectly networked computer”.
Second after second, he notes, the pancreas secretes just the right amount of insulin or glucagon to lower or raise blood sugar in the portal vein, which leads directly to the liver, the site of the most important metabolic processes. The insulation is then distributed to every tissue in the body via the general circulation.
“Insulin injections are life-saving, but they are administered under the skin and nowhere near as precise,” says Lewis, who is also a scientist and professor in the Department of Physiology and Medicine at the University of T. “It is extremely difficult to mimic the functioning of a healthy pancreas. ”
This is one of the reasons a cure for diabetes has proven elusive 100 years after the discovery of insulin.
Another important reason is the complexity of the development of the disease. In type 1 diabetes, the immune system destroys the insulin-producing beta cells in the pancreas, causing life-threatening increases in blood sugar. Type 2 diabetes usually occurs more slowly as the body becomes resistant to insulin or the pancreas cannot produce enough of it.
Genetics play a role in both types. Exposure to viruses and other environmental factors can be a factor in Type 1. Lifestyle factors, including weight gain and physical inactivity, are strongly linked to Type 2.
The bottom line, Lewis says, is that diabetes is a multifactorial disease and we are not close to a cure.
Ask about treatments, however, and Lewis gets excited.
The past two decades have seen a multitude of clinical and scientific advances, from new drugs to increase and sensitize the body to insulin and promote weight loss, to measures to improve lifestyle, continuously monitor blood sugar levels, and long and short-term Insulin, better insulin pumps, pancreatic transplants, and preclinical stem cell and immunosuppressive therapies.
“The progress in treatments has been fantastic, especially for Type 2,” says Lewis. “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, the distinction becomes less and less important when the goal is a full and healthy life.
Type 2 diabetes accounts for about 90 percent of all diabetes cases in Canada. The prevalence is increasing, but Canadians with type 2 diabetes live longer and have fewer complications related to diabetes.
“The clinic doesn’t look like it did 30 years ago,” says Lewis, who mainly treats type 2 patients. “We see fewer amputees, less blindness. Patients are generally healthier and their prognosis is often excellent if they maintain their blood sugar goal and other key parameters. “
Weight loss is a cornerstone of treatment for lowering blood sugar, and recent research has strengthened the link between weight loss and type 2 diabetes management. Some people with Type 2 can lose weight and control blood sugar through diet and exercise alone.
Bariatric surgery is very effective for weight loss and often leads to diabetes remission, although it is surgical risk and expensive.
“If we could prevent obesity, we could significantly reduce the incidence of type 2,” says Lewis. “And experiments have shown that with lifestyle changes we can get into remission so we know what is working.”
The problem is a broad implementation.
“I’ve tried losing weight and I know how difficult it can be, especially in an environment with convenient and inexpensive calories,” says Lewis. In addition, 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 determinant of who gets type 2 diabetes and how well or poorly they deal with it,” says Lewis.
Fortunately, dozens of new drugs for diabetes have appeared on the market over the past two decades.
Drugs for weight loss round off the armament and some also protect against kidney damage and lower heart risk. Current therapies can reduce body weight by up to 10 percent, although a loss of 20 percent or more would have a greater impact on outcomes in patients with type 2 diabetes, says Jacqueline Beaudry, an assistant professor of nutrition at U of T who studies relationships between obesity, hormones, and diet.
Beaudry is studying the biology underlying these drugs, including the gut hormones GLP-1 and GIP. They control blood sugar and reduce appetite, but scientists aren’t sure how.
“If we could understand how they work, we could develop better drugs,” says Beaudry.
For people with type 1 diabetes, continuous glucose monitors, insulin pumps, and even automated “closed-loop” systems that run on mobile apps to deliver insulin on demand have radically changed the patient experience.
Sara Vasconcelos (left), an assistant professor at the Institute of Biomedical Engineering at T University, collaborated with Cristina Nostro (right), Associate Professor in the Department of Physiology, and her team at UHN’s McEwen Stem Cell Institute to improve the survival and functionality of pancreatic progenitor cells generated from human stem cells.
Cell therapy could prove to be even more liberating.
University laboratories and biotech companies are working on implantable devices that house insulin-producing cells made from stem cells.
To this end, Cristina Nostro, Associate Professor in the Department of Physiology at the Temerty Faculty of Medicine, and her team at the University Health Network’s McEwen Stem Cell Institute recently discovered a more efficient way in the laboratory to create and purify pancreatic progenitor cells from human stem cells.
They also found a way to vascularize these cells by working Sara Vasconcelos, Assistant Professor at the Institute of Biomedical Engineering at the University of T. Together, they expanded the survival and functionality of cells in animal models of diabetes.
The biggest problem with these therapies is that the immune system rejects them. The same challenge is currently hindering pancreas and islet transplants.
“The immune system is an amazing machine, we’re lucky it’s that good,” says Nostro. “But it’s very difficult to control when it goes wrong, like under autoimmune conditions.”
Nostro is working with university immunologists on a way to protect insulin-producing beta cells from immune rejection, and she says many researchers in the area are now focusing on immune-protective approaches.
Another strategy for type 1 diabetes is to suppress the autoimmune response before the disease progresses. The idea is to prevent immune cells from damaging the pancreas while the body is still producing beta cells.
“Groups around the world bring different ideas and creative approaches to treating type 1 diabetes, that’s the beauty of science,” says Nostro. “I am very hopeful of what the future will bring. Who knows? Maybe we’ll see hybrid technologies that combine a pump and cells. We have to be open. “
This story was originally published in the insulin issue of U of T Med Magazine.
