Active Voice: What Limits the Exercise Response of the Diabetic Heart?
By J. Chris Baldi, Ph.D., FACSM, and Genevieve A. Wilson, BSc (Hons)
J. Chris Baldi, Ph.D., FACSM, received his Ph.D. in exercise physiology from the Ohio State University and currently is a senior research fellow at the Dunedin School of Medicine at the University of Otago in New Zealand. His research is broadly focused on the cardiovascular responses to exercise in clinical populations, with a specific interest in left ventricular responses to acute exercise and chronic exercise training in people with diabetes.
Genevieve A. Wilson, BSc (Hons), is a Ph.D. candidate at the University of Otago in Dunedin, New Zealand. Her research focuses on the cardiovascular stress response in people with type 2 diabetes and how high intensity interval training (HIIT) influences heart function.
This commentary presents Dr. Baldi’s and Ms. Wilson’s views on the topic of a research article, which they authored with other colleagues. Their article appears in the May 2017 issue of Medicine & Science in Sports & Exercise® (MSSE).
The global burden of type 2 diabetes is immense, given that there are an estimated 382 million diagnosed cases worldwide. Improved blood glucose control has resulted in significant reductions in complications, such as retinopathy and nephropathy, that are associated with this disease. Unfortunately, the same improvements are not seen with cardiovascular disease, which accounts for 50 to 80 percent of all deaths in people with diabetes. Aerobic capacity is the best predictor of cardiac and all-cause mortality; therefore, exercise training is particularly important for people with diabetes. Unfortunately, the capacity of the diabetic heart is often reduced, making it harder for these patients to exercise effectively. More specifically, both heart rate and pump function (contractility) increase less during exercise in patients with diabetes, when compared with these responses in nondiabetic people who have similar demographic profiles. Consequently, people with diabetes are less able to increase their cardiac output during heavy exercise.
The autonomic nervous system, which includes parasympathetic (“rest and digest”) and sympathetic (“fight or flight”) branches, is the primary influence driving the heart’s response to exercise. The balance of these two “offsetting” branches controls the functional state of the heart. During exercise, high resting levels of parasympathetic activity to the heart are withdrawn and sympathetic release of catecholamines (adrenaline and noradrenaline) increases progressively, in proportion to exercise intensity– thus, raising heart rate and increasing contractility. Because cardiac output (the product of heart rate and stroke volume) is often reduced during exercise in people with type 2 diabetes, we hypothesized that this resulted because people with diabetes have a reduced “responsiveness” to their own catecholamines.
In our study, as described in the May 2017 issue of MSSE, we tested this hypothesis by comparing echocardiographic images of the heart in people with type 2 diabetes against nondiabetic control subjects. The challenge protocol we used with these two study groups involved drug infusions which mimicked the autonomic nervous response seen during incremental exercise. First, a large dose of atropine was given to abolish the activity of the parasympathetic nervous system. This caused a similar increase in heart rate (up to about 110 beats per minute) and cardiac output in both groups. Then, to test our hypothesis, we infused dobutamine, a “synthetic adrenaline,” by increasing doses until heart rate achieved 85 percent of the maximum value that we had previously obtained with these subjects during a functional capacity test.
As expected, people with type 2 diabetes had lower aerobic capacity than the nondiabetic group. Contrary to our hypothesis, we found the heart rate, stroke volume and ejection fraction (the percentage of blood ejected from the left ventricle during each beat) responses to incremental dobutamine infusions were the same in people with and without type 2 diabetes. However, despite the similarity in the exercise response, the hearts of people with diabetes had smaller stroke volumes and ejection fractions throughout the infusion protocol. Essentially, this means that the hearts of people with uncomplicated diabetes appear to be capable of responding normally to the catecholamines released by their sympathetic nervous system. The inability to increase cardiac output, instead, may be explained by the fact that these hearts appear to work at smaller volumes.