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Dr. Todd Duhamel
Principal Investigator, Physical Activity and Chronic Disease Prevention
Institute of Cardiovascular Sciences
Research Focus
Creating a link between Kinesiology and the Cardiac Sciences
Diabetes mellitus is one of the fastest growing chronic diseases in Canada, affecting more than 2 million Canadians. Diabetes is a metabolic disorder characterized by defective insulin signaling, hyperglycemia and hyperlipidemia, which cause cellular damage and organ failure. Insulin-dependent (Type 1) diabetes mellitus is characterized by pancreatic -cell dysfunction and insulin deficiency that can be treated with insulin injections. The natural history of non-insulin-dependent (Type 2) diabetes mellitus is different from Type 1 diabetes, as tissue insulin-insensitivity is the prominent clinical problem. Initially, a compensatory hyperinsulinemia is able to maintain glucose homeostasis in spite of tissue insulin-insensitivity in this patient group. However, pancreatic -cell function ultimately becomes impaired and hyperinsulinemia cannot be maintained at a level sufficient enough to prevent the development of hyperglycemia. Insulin injections cannot adequately treat Type 2 diabetes. Epidemiological studies have estimated that greater than 6% of the population has diabetes. However, diabetics represent a disproportionately greater segment of the population diagnosed with cardiac dysfunction. In fact, an increased incidence of cardiovascular disease is the most common complication of diabetes, as 4 out of every 5 deaths in diabetic populations can be attributed to cardiovascular diseases. One factor contributing to the high incidence of heart disease in this population is the fact that diabetes promotes the pathological remodeling of cardiac proteins at the level of the cardiomyocyte (the contractile cell in the heart), which impairs the ability of the heart to pump blood effectively (commonly referred to as diabetic cardiomyopathy).
Sufficient physical activity is a prerequisite for health. In fact, physical activity is widely accepted as a pillar for the prevention of Type 2 diabetes, as people that are insufficiently physically active (i.e.; those who lead a sedentary lifestyle) are at an increased risk of developing Type 2 diabetes compared to individuals who engage in regular physical activity. Even so, we still do not fully understand the biological mechanisms to explain how physical activity facilitates health. Part of the reason for this deficiency is that we still have not defined the minimum or optimal doses of physical activity required to maintain health. Several studies have indicated that the beneficial effects of regular physical activity may depend on the intensity and volume of exercise performed. However, controversies associated with the clinical feasibility of moderate and high intensity exercise training protocols still exist. Specifically, there is concern that high intensity exercise protocols may not be appropriate for Type 2 diabetes patients because this population tends to have reduced aerobic fitness and impaired cardiac function compared to healthy individuals. Therefore, one of the objectives of my research program is to characterize the potential health benefits of two clinically relevant physical activity interventions. One intervention will employ a voluntary exercise model where participants individually select the intensity, duration and frequency of physical activity completed. The second intervention will employ a prescribed high-intensity interval running model where participants will run on a treadmill for 1 hour per day, 5 days per week using an intermittent interval running program where they complete a 10 minute warm-up run at 50% of their aerobic fitness level followed by intervals of 2 minutes at 85-90% of their aerobic fitness level followed by 2 minutes at 40-50% of their aerobic fitness level. These interventions are similar to the voluntary walking programs or prescribed exercise interventions being utilized to reduce the prevalence of Type 2 diabetes in society. Our rationale for including both physical activity interventions is to directly compare the potential clinical benefits of each approach by determining if these physical activity models improve cardiovascular function in Type 2 diabetes. I envision a research program that will combine experimental research with clinical initiatives. Therefore, I will utilize isolated cell models, animal models as well as human volunteers to conduct this physical activity-based research program. My basic science program will focus particular attention to identify the cellular and molecular processes that regulate muscle metabolism and calcium transport proteins during a single bout of physical activity or in response to physical activity training.
Sarcoplasmic reticulum (SR) calcium-transport proteins regulate the rapid changes in calcium-transients within the heart and, therefore, are positioned as key regulators of cardiac contractility. One factor known to contribute, at least in part, to loss in cardiac contractility in the diabetic heart is the reduction in SR protein function and expression that occur as a result of the diabetic state. Physical activity may have the power to restore myocardial calcium transport and contractility in the diabetic heart. Indeed, physical activity training is known to improve cardiac contractility in healthy animals and also following a myocardial infarction. This improvement in cardiac contractility following physical activity training occurs, at least in part, due to metabolic adaptations as well as an increase in calcium-transport protein function. Interestingly, a strong correlation between aerobic fitness and myocardial calcium handling has been identified in several studies that have characterized these parameters in models of physical activity, physical inactivity (sedentary lifestyle leading to a reduced fitness level), or myocardial infarction. However, very little research has been conducted to determine the biological mechanisms to explain the link between aerobic fitness and calcium transport in cardiac muscle. As a result, my research program will commit a particular emphasis to identify the biochemical and molecular mechanisms that are activated by physical activity to restore normal calcium-transport function within the diabetic heart.
My clinical/applied research program will answer similar research questions in humans by securing skeletal muscle tissue samples (muscle biopsy) from healthy as well as patient populations. My clinical research program will also advocate health promotion by supporting the utilization of clinical exercise rehabilitation programs for the prevention or treatment of diabetes and cardiovascular disease. To facilitate this clinical research program, I plan to create links with regional diabetes prevention programs as well as cardiac rehabilitation programs within the community. By integrating experimental and clinical initiatives, my research program will be positioned at a point where it can translate knowledge derived from the molecular and cellular discoveries made in the laboratory into messages that will improve cardiovascular health in diabetic populations.
Why is this work important?
Physical activity is viewed as a viable approach for the prevention and treatment of many chronic diseases, including cardiovascular disease, type-2 diabetes, and some cancers. Insufficient physical activity is the single largest risk factor contributing to development of chronic diseases in the world today. For example, epidemiological studies have indicated that greater than 65% of the people in North American are not physically active enough to maintain their health. A greater concern for the health of Manitoban’s, is the fact that less than 10% of our children meet current physical activity guidelines. If this trend continues, it is expected that 1/3rd of our children will develop type 2 diabetes by the time they reach 20 years of age. This should concern parents as diabetics tend to have a life-expectancy that is ~7 years shorter than non-diabetic populations. Diabetes is also a major risk factor for the development of many cardiovascular diseases, which could be expected to further reduce the life expectancy of our children as cardiovascular diseases tend to develop much earlier in diabetic patients compared to the general population. Physical inactivity is also a major concern for the health care system, as health care expenditures associated with diabetes exceed $13 billion per year.
Historically, society has viewed physical activity as a leisure activity, a work (labor) activity or a sports-associated endeavor. However, there is a paradigm shift occurring in the world today, which is leading to the view that there is a minimum amount of physical activity required to maintain health. In fact, there is a compelling amount of data to suggest that insufficient physical activity induces genetic changes, which promote the development of chronic diseases and lead to the manifestation of pathological symptoms, by activating “disease-promoting” genes and by inhibiting “health-promoting” genes. Conversely, there is a growing body of evidence indicating that regular physical activity reduces the impact of chronic diseases, such as cardiovascular disease, type-2 diabetes, and some cancers, by activating “health-promoting” genes and by inhibiting “disease-promoting” genes.
What techniques and equipment are used in this laboratory?
Although there is a growing body of evidence indicating the health benefits of physical activity, we still do not clearly understand the mechanisms to explain how physical activity has such a beneficial effect. Therefore, my research program has been designed to identify the cellular and molecular mechanisms that are activated by physical activity to maintain health. With this objective in mind, my basic biomedical research program will utilize various models of physical activity and inactivity to examine novel cellular and molecular processes that influence the development of chronic diseases.
We plan to employ a range of animal models of Type 1 diabetes (streptozotocin induced Type 1 diabetes), dietary induced insulin-insensitivity (high western fat feeding, sucrose feeding), as well as genetic models of type 2 diabetes (ob/ob mice or db/db mice). The physical activity models that we employ for our animals studies are based on two clinically relevant physical activity interventions (8 weeks in duration). The first intervention will utilize spontaneous wheel running, where animals individually select the intensity, duration and frequency of physical activity completed. The second intervention will utilize prescribed high-intensity interval running, where rats will run on a treadmill for 1 hour per day, 5 days per week using an interval running program where they complete a 10 minute warm-up run at 50% of their aerobic fitness level followed by 5 intervals of 8 minutes at 85-90% of their aerobic fitness level followed by 2 minutes at 60-65% of their aerobic fitness level. It should be indicated that this physical activity pattern simulates the activity patterns that many animal voluntarily choose to do every day. Moreover, these interventions are similar to the voluntary walking programs or prescribed exercise interventions being utilized to reduce the prevalence of T2Dm in society.
To analyze tissue sample, we utilize several biochemical, cellular and molecular assessment techniques in our laboratory to examine the changes that occur in response to models of physical inactivity, physical activity in combination with our chronic disease models. We also assess functional changes in muscle and cardiac contractility through the use of echocardiography technologies, miniature catheterization technologies, and isolated tissue (cell culture and isolated muscle) technologies. Our laboratory also has access to equipment that can detect and analyze proteins (Western blot) and RNA (real-time PCR). Fluorescent, spectrophotometric and radioactive assays can be employed to characterize changes in protein function in tissue homogenates and isolated fractions.
Dr. Todd Duhamel
Dr. Todd Duhamel was born in Atikokan, Ontario. After completing his undergraduate degree in Kinesiology at the University of Waterloo, he went on to complete a Ph.D. in the field of skeletal muscle physiology in the laboratory of Dr. Howard Green at the University of Waterloo. To complete his academic training, he finished a 2 year postdoctoral fellowship placement within the Institute of Cardiovascular Science at the St. Boniface General Hospital Research Centre. Dr. Duhamel is a recently recruited Assistant Professor in the Faculty of Kinesiology and Recreation Management, University of Manitoba. His research program brings a distinct expertise to the Institute of Cardiovascular Sciences, as he has a particular research emphasis examining the role of physical activity for the prevention, as well as treatment of cardiovascular disease in diabetes.
For more information, please contact:
Dr. Todd Duhamel
Ph. (204) 235-3589
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