Doctors' Notes: New Research Aims to Curb Diabetes Complications

Republished from the Toronto Star

As an endocrinologist, I help people with a range of illnesses related to their diabetes. I see how diabetes that is left untreated or poorly managed can wreak havoc on parts of the body like the nervous system, liver, heart, or kidneys.

More than 3 million Canadians live with diabetes; according to Diabetes Canada, that number is expected to reach 5 million by 2025.

The disease is at the root of a huge number of devastating complications — which are expected to rise along with the increase in people affected.

Diabetes is a leading cause of cardiovascular disease, blindness, kidney failure and lower limb amputation. For example, 80 per cent of new cases of dialysis or kidney transplantation are related to diabetes. And so far, no drugs can block this kind of end-stage renal disease.

In my lab, which is part of U of T’s Banting and Best Diabetes Centre, we are looking for ways to reduce or prevent diabetes-related kidney problems. In particular, my team and I have found two proteins that seem to play important roles in the development of complications. We want to learn more about how these proteins work, and how we might control their function to prevent problems in the first place.

But we’re not the only ones doing this type of work. Scientists around the world are taking their research in exciting new directions to prevent diabetes complications.

Last month, researchers from the University of Toronto and Paris Descartes University gathered in Toronto to share information about some of the newest developments that could one day help people ward off these dangerous complications.

Here are a couple of interesting areas of research:

Increasingly, inflammation is being explored as a contributor to insulin resistance, which can lead to diabetes in the long-term.

Under normal circumstances, inflammation protects us from bacterial or viral infections. But when there is too much fat going into the body’s cells, especially the ones that don’t normally take up fat like liver or muscle cells, this can cause insulin resistance.

When the body is fighting an infection, the insulin resistance may help keep glucose levels up to provide energy to ward off the illness. But in the case of ongoing insulin resistance without infection, insulin can’t do its normal job to help our tissues absorb glucose. We’re still trying to understand it, but we’re learning how abnormal inflammation raises the risk of high blood sugar and diabetes.

Another aspect of inflammation scientists are watching is its relationship with the bacteria that normally live in the gut, known as the microbiome.

Studies show that people with obesity seem to have a different balance of bacteria living in their digestive systems than people who are lean. Managing these tiny organisms may also help control blood sugar.

Researchers are still piecing together the variety of factors that affect the microbiome, like genetics and diet. For instance, eating too many sweets will cause changes to the microbiome’s composition and can lead to inflammation. One question some of my colleagues hope to solve is whether tools like probiotics could help people replace bad organisms in their intestines with good ones to keep their blood sugar in a healthy range.

Intestinal flora might also have an impact on weight, which is associated with type 2 diabetes. There is growing curiosity in the scientific community about gut microbiome transplants and how they might affect the balance of good and bad bacteria to help people manage their weight. For example, in mice, some experiments found that stool from an obese mouse transplanted into a lean mouse caused weight gain. And the opposite was observed when the fecal transplant went from a lean to an obese mouse, so the obese mouse lost weight.

In other ways we’re on the verge of new treatments and therapies that could go a long way to helping people with diabetes live healthier lives.

There are drugs being tested that seem to block fibrosis, which is an end-stage response that can occur in the kidneys and the liver. Liver inflammation and cirrhosis, similar to that caused by excess alcohol intake, can also be caused by obesity and diabetes. When it comes to how the process occurs in different tissues, there are commonalities between these organs. One day, we may be able to use one drug to target problems in more than one part of the body.

It’s an exciting time to be doing this kind of work — but also an urgent one. And for so many people struggling to manage complications, the new tools can’t come too soon.

Dr. I. George Fantus is a professor in the Departments of Medicine and Physiology at the University of Toronto’s Faculty of Medicine. He is also director of the core laboratory of U of T’s Banting and Best Diabetes Centre, associate member of the Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital as well as senior scientist at the Toronto General Hospital Research Institute. Doctors’ Notes is a weekly column by members of the U of T Faculty of Medicine. Email doctorsnotes@thestar.ca