BBDC Member Profile

Mamatha Bhat, MD, MSc, PhD, FRCPC

September 8, 2021
By Krista Lamb

photo of Mamatha BhatFatty liver disease and type 2 diabetes are conditions that are commonly linked to each other. For liver transplant recipients, this means an increased likelihood they will develop diabetes post-transplant. For those who have type 2 diabetes pre-transplant, this must be factored into their post-transplant care. These are the issues that inform the research of Dr. Mamatha Bhat, a hepatologist and clinician-scientist at UHN’s Multi-Organ Transplant Program and an Assistant Professor in the University of Toronto’s Division of Gastroenterology.

Bhat grew up in an environment where there were many role models for a career in medicine and where her love of research was nurtured and encouraged. In medical school, she chose mentors who were clinician-scientists, looking at how she could balance academia and clinical practice. It was during this time that she discovered her interest in studying the liver. “I always found the liver to be a fascinating organ, and it’s quite relevant to diabetes and metabolic disease,” she says.

“When I entered medicine, my idea was to do something like obstetrics or pediatrics. Then along the way, I met these very inspiring liver specialists at the hospital where I did my internal medicine training. And I got to work with the patient population and appreciate the complexity and the beauty of the liver. It’s the metabolic factory of the body, and it performs hundreds of functions that people really don’t appreciate. It produces clotting factors. It produces proteins that regulate the hormone levels. It transforms sugars into fats and then proteins. There’s this whole slew of functions that the liver produces, and it’s such a complex organ, both anatomically and biochemically.”

Now a highly-regarded liver transplant specialist with a practice of close to 400 liver transplant recipients, Bhat has also begun to appreciate the unique ways that the liver and diabetes are connected. “One very important thing that people don’t realize is that fatty liver disease is a manifestation in a way of diabetes. When you think of diabetes, most people will think of kidney and heart, but really the liver is the metabolic factory and it plays a crucial role in the regulation of blood sugar. And when there is insulin resistance, there is accumulation of fat within the liver, which then can be associated with inflammation over time and ultimately the development of cirrhosis. So most patients with fatty liver disease also have diabetes. And a significant proportion of individuals with diabetes have fatty liver disease and vice versa. Over 70 percent of individuals with diabetes will have fatty liver disease,” she explains

For liver transplant recipients this connection is even more stark. These days, patients tend to do quite well over the crucial first year, but beyond that their long-term outcomes can be compromised by their increased risk of diabetes, hypertension, dyslipidemia, and heart disease. “The reality is that although patients have received a lifesaving transplant, their long term-survival is unfortunately compromised by a death due to metabolic disease and cancer that is higher than in the general population. My research program is interested in understanding the mechanisms behind that and developing more personalized strategies to improve our management of diabetes and fatty liver disease in transplant recipients, because there isn’t very much known about that,” says Bhat, who feels strongly that we must look to enhance quality and quantity of life long-term after transplant.

While some patients have pre-existing diabetes, for others there are factors that contribute to the increased risk after transplant. This may be because of immunosuppression drugs, which can impact pancreatic beta cells and insulin secretion. There is also the potential for weight gain due to increased insulin resistance. Recipient age can also be a factor.

“Metabolic disease tends to behave much more aggressively in transplant patients than in the general population. Fatty liver disease as a manifestation of post-transplant diabetes tends to progress more aggressively as well,” says Bhat.

Currently, most transplant physicians just use the known therapies for those without a transplant to manage metabolic disease, which is not ideal. Bhat hopes her research findings will help to guide clinicians and to better support transplant recipients and increase overall health and long-term survival rates.

“The interesting thing about the research we are doing is that it’s not simply applicable to transplant recipients. We can learn lessons from this and help inform knowledge of diabetes in general. There are a number of different patient populations who are on immunosuppression and also have a higher risk of metabolic disease as compared to the general population. And so we might use these lessons to better understand the role of environmental exposures, epigenetic changes, et cetera, and modulating more aggressive forms of metabolic disease,” she says. “Ultimately I want to help transplant patients. But I think there are lessons that we can derive from this to also better understand diabetes more globally in other patient populations.”