December 01, 2021 The gene factor

Who:

Dr. Satya Dash, assistant professor, Division of Endocrinology, Toronto General Hospital

Research highlights/discoveries:

• Studying patients who have severe obesity, a risk factor for type 2 diabetes

• Finding that some patients have changes in their genes that put them at risk for mental health conditions and increased weight gain

Dr. Satya Dash at a glance:

• Received a Diabetes Investigator Award from Diabetes Canada (2017)

• Awarded the Reuben and Helene Dennis Scholarship, Banting & Best Diabetes Centre (2016)

• Moved to Toronto to join the Banting & Best Diabetes Centre at University of Toronto (2011)

• Earned his PhD from Cambridge University, England (2011)

• Awarded a Medical Research Council Clinical Research Fellowship, Cambridge University (2006)

• Earned his medical degree from St. Bartholomew’s Hospital Medical College, London (England) (2000)

How did you get interested in diabetes and genetics?

During my endocrinology training, I was lucky to do my PhD under the supervision of Sir Stephen O’Rahilly, a leader in the research of obesity and insulin resistance. In my first paper, we described the first human genetic mutation [found in one family] that affects how glucose [sugar] is taken up by muscle and fat, and causes severe insulin resistance. Environmental factors—such as body weight, pregnancy, and puberty—worsened the effects of the mutation. A fundamental question to answer is, why do some people get insulin resistance and diabetes if they have excess weight?

How do you think insulin resistance, diabetes, and excess weight are connected?

Obesity, which increases your risk of diabetes, is to a large extent influenced by genes. We now have more than 250 obese patients [with a body mass index, or BMI, of more than 50] enrolled in our study. In our early findings, we have found that 15 per cent of them have genetic mutations which predispose them to mental health concerns. We also think that these genetic changes play a role in obesity. Now we’re looking at what is happening in the other 85 per cent of the people in the study: Interestingly, many have not developed diabetes or insulin resistance. We think genetic factors are important in protecting these patients from diabetes, and are working to find what those factors are.

What do you want to learn from your research?

There is still a lot of stigma associated with excess weight and diabetes—and mental health. I’m hoping our findings will make people realize it doesn’t always come down to a lack of willpower or choice.

Bariatric surgery is the most effective weight-loss treatment for type 2 diabetes, but we don’t understand how it works. Genetic factors are important in how people respond to surgery, so we are interested in finding these factors to better understand why this surgery works for people with type 2 diabetes.

We have some very preliminary data that genetic factors are likely important in determining remission of type2 diabetes after bariatric surgery. We are actively working on that currently.

Among people with T2D, the benefits of bariatric surgery are not always appreciated. We recently reported that approximately 69% of patients who are referred for surgery—currently the most effective treatment for T2D—decline it. Many are concerned about having an invasive procedure. Interestingly, those who do have surgery are less likely to have heart and kidney disease, and to live longer. I hope this persuades more people to

What else are you working on now?

We’re studying how body weight and blood sugar are regulated, using treatments that act on the brain. Unfortunately, most people who lose weight, regain it. One major reason is that the amount of energy spent by the body goes down. A treatment that increases the amount of energy spent would be useful, but none currently exist. Glucagon is a hormone that can increase the energy that is spent by the body when given as an injection, but it also raises blood sugar. We recently showed that giving glucagon as a spray [instead of an injection] increases energy without raising blood sugar for 90 minutes by potentially acting on the brain. The effects were most prominent within the first 25 minutes, but it would be interesting to see what effects longer-acting preparations would have.

The last word

“Dr. Dash’s research is significant not only because it looks at the role genes play in type 2 diabetes, but it also considers the impact on mental health, and obesity. If we are to End Diabetes and the diabetes epidemic, it’s crucial that we change the conversation away from blaming the individual to understanding the interaction between genes, the environment and individual behaviours.” — Dr. Seema Nagpal, vice president, Science & Policy, Diabetes Canada

Did you know?

2021 marks the 100th anniversary of the discovery of insulin. Today, more Canadians have diabetes than ever before. Diabetes or prediabetes affects one in three Canadians. One in two young adults will develop diabetes in their remaining lifetime. We cannot wait another 100 years to fund vital research that can help End Diabetes. #LetsEndDiabetes Visit 100 Years of Insulin to learn more, including how you can support those living with or at risk for the disease.

(This article appeared in Diabetes Dialogue, Summer 2019.)