World-class research on the road to a diabetes cure
Gregory Steinberg has received Diabetes Canada funding to research ways to ramp up the body’s metabolism to burn fat and sugars to avoid the development of diabetes. Supplied
Diabetes Canada instituted a new research-funding model in 2017 to deliver maximum impact for the amount of money invested. The goal is to make significant strides by 2021, the 100th anniversary of the discovery of insulin by Canadian researchers Drs. Banting and Best.
“By 2021, we want to change the world for people affected by diabetes through advances in prevention, care and treatment, and to mobilize research dollars so that we can fund the research for a cure,” says Dr. Jan Hux, president and CEO of Diabetes Canada.
Diabetes Canada-funded researchers are also searching for new knowledge about diabetes complications, such as retinopathy and heart disease. Finding ways to alter disease-causing biological mechanisms could lead to new prevention strategies and treatments.
Curbing vision loss from diabetes
Diabetic retinopathy is the most common complication of diabetes and the leading cause of blindness in working-age individuals. It is currently estimated that 500,000 Canadians have diabetic retinopathy, and the incidence is expected to double over the next 15 years.
Diabetes Canada supports research by Dr. Przemyslaw (Mike) Sapieha, a scientist at the Université de Montréal and Canada Research Chair in Retinal Cell Biology, as he searches for greater understanding of how high blood glucose (sugar) levels contribute to vision loss in people with diabetes and ways to counteract these effects.
“We know that one of the best ways to reduce the risk of diabetic retinopathy is to have good control of your blood sugar levels,” says Dr. Sapieha. “High blood glucose tends to cause a series of reactions that cause a degeneration of the blood vessels in the retina.”
One of the earliest complications causing vision loss is “diabetic macular edema” – swelling of the part of the retina called the macula. Later in the course of disease, blood vessels can start to die off, cutting off the flow of oxygen and nutrients to the cells of the retina that transmit pulses of light to the brain. In later stages, the retina may also try to compensate for the loss of blood vessels by creating new ones in a disorganized fashion – which may lead to further and often, more serious damage to vision.
Dr. Sapieha has also discovered cellular interactions and intracellular mechanisms that govern vessel growth and which may unlock new avenues of treatment.
“Diabetic retinopathy has been labelled almost uniquely as a microvascular disease and, traditionally, most treatments targeted retinal vessels or factors that affect vessels,” he explains. “Our research has shed light on early changes in the retina’s neurons and how these neurons ultimately produce factors that affect blood vessels and vision loss from diabetes.”
Dr. Sapieha has uncovered a unique mechanism in neurons in the parts of the retina where blood vessels have died. The neurons go into a dormant state where they’re not functioning, but are not dead.
“The idea is to understand what programs are being activated in those neurons to prevent them from dying, and determine if we can use therapies to ‘wake them up.’
“We think this opens up possible new treatments to kickstart these dormant neurons to function again, thus restoring vision for people who may have been without sight for a long time,” says Dr. Sapieha.
Metabolism, obesity and diabetes
The growing number of Canadians who are overweight or obese is an important factor contributing to the rising incidence of type 2 diabetes, and one research goal is to identify at the molecular and cellular level ways to prevent this from happening. The aim is to answer the question, “How can we prevent type 2 diabetes in people who are overweight or obese?”
Diabetes Canada-funded researcher Dr. Gregory Steinberg is addressing this question by investigating the complex metabolic processes operating in the obesity-diabetes link, as well as the links of both diseases to cardiovascular disease (CVD).
“Obesity, type 2 diabetes and CVD are interrelated metabolic diseases,” says Dr. Steinberg. “We are working on ways to ramp up the body’s metabolism to burn fat and sugars to avoid the development of diabetes and CVD.”
Dr. Steinberg is a professor of medicine at Hamilton’s McMaster University and Canada Research Chair in Metabolic Diseases. He is also the co-director of McMaster’s new Centre for Metabolism, Obesity and Diabetes Research.
Normally, fat is stored in fat cells in the body, Dr. Steinberg explains. With obesity, a person may start to store fat in other tissues, such as the liver, which leads to inflammation and resistance to insulin, the key hormone that keeps blood glucose levels low. Thus accumulation of lipids (fatty acids and cholesterol) in the liver can cause blood sugar levels to rise, causing diabetes.
“It becomes like a snowball rolling downhill – the accumulation of lipids in the liver can happen quickly with weight gain, triggering a vicious cycle of insulin resistance, high blood glucose and a greater risk of having a heart attack or stroke.
“The goal is to find new ways to prevent and treat diabetes by increasing energy metabolism and fat burning, potentially by targeting inflammation and hormonal factors.”
Increasing energy metabolism with therapies would help people who are overweight or obese overcome the challenges of maintaining weight loss through diet and exercise – presenting new hope for people at risk for type 2 diabetes.
“We know that modest weight loss can prevent type 2 diabetes from developing in many people,” says Dr. Steinberg. “But keeping weight off is difficult, because people’s metabolism slows down. Finding new ways of keeping the metabolic furnace running could have a tremendous impact on the diabetes epidemic.”