How Adipose Tissue Impacts Exercise Tolerance 

Can the amount of fat on the heart impact a person’s exercise intolerance?   

Regardless of age or smoking status, type 2 diabetes is a risk factor for heart failure. Unfortunately, exercise intolerance, which also increases a person’s risk for developing heart failure, is a symptom of type 2 diabetes. Exercise capacity can partially be determined by left ventricular structure and function. Epicardial adipose tissue (EAT) is an ectopic fat that is used as an index of cardiac adiposity. In people with type 2 diabetes, EAT accumulates at a faster rate than in those without diabetes.  

The authors of this study were unable to find any previous study that looked at the association between EAT, left ventricular structural and functional abnormalities, as well as between EAT and exercise capacity. As such, the authors wanted to clarify any association between these factors. They hypothesized that people with type 2 diabetes with stage A or B heart failure would have an increased EAT volume and exercise intolerance when compared to matched healthy individuals. An additional hypothesis was that EAT volume and exercise intolerance would increase as left ventricular abnormalities increased, and that EAT could be used as an index relating left ventricular structural and functional defects to exercise intolerance. The study recruited 382 people, 176 of whom had type 2 diabetes with asymptomatic heart failure and 62 as healthy individuals for a control group. As this study took place in Japan, a BMI of ≥25 was defined as obese, per the Japan Society for the Study of Obesity criteria. Echocardiography was used to identify any left ventricular structural and functional abnormalities to establish each participant’s baseline. The researchers examined left ventricular posterior wall thickness and interventricular septal thickness at end-diastole, left ventricular end-diastolic and end-systolic diameter, as well as the left ventricular diameter and wall thickness. Echocardiography was also used to measure EAT. Exercise capacity was measured by cardiopulmonary exercise testing through the use of an ergometer to provide peak VO2, anaerobic threshold, peak oxygen pulse, and delta heart rate. EAT and peak VO2 were compared using age- and sex-adjusted analysis of covariance, with or without the presence of left ventricular abnormalities. 

At baseline, age, sex, BMI, BSA, and the percentage of people with hypertension were not significantly different between the three groups. Lipid and glucose metabolism, as well as eGFR, were worse in the heart failure groups than in control. Use of blood pressure medications was higher in the group with stage B heart failure when compared to those with stage A. While the left ventricular function of those in the stage B heart failure group was worse than for those in the stage A group, there was no significant difference in the ejection fraction or stroke volume between the two. The EAT was thicker in the group with heart failure than the control group, with the stage B group having the thickest EAT. Similarly, the peak VO2 was significantly lower in the heart failure groups than the control, as were the heart rate and delta heart rate. In the three groups, the control group did not have any abnormalities. About half (49.2%) of the stage A group had functional anomalies, though none had structural abnormalities. All the people in the stage B group had structural and functional abnormalities. Even when the participants were matched based on age, sex, and BMI, EAT was thicker and peak VO2 was lower in the people who had heart failure. EAT was again thicker and peak VO2 lower in those where the left ventricle had some structural or functional abnormality. As these left ventricular abnormalities increased, the EAT became thicker and peak VO2 decreased even more. Lastly, this study found that EAT was independently associated with peak VO2, also when other factors were controlled for. Previous studies have shown that EAT begins accumulating during pre-heart failure stages, such as type 2 diabetes.  

This cross-sectional study found that EAT may be independently associated with exercise capacity indicators. Because this study is a cross-sectional study, it is impossible to say that there is a causal relationship between EAT thickness and exercise capacity or heart rate response. While this study provides a proof of concept for the study of EAT thickness in the future, its results need further research.  

Practice Pearls: 

• EAT appears to be associated with exercise capacity indicators. 
• As exercise intolerance and type 2 diabetes are both risk factors for developing heart failure, it is essential to ensure prompt treatment to minimize associated risks.  
• Further research is needed to clarify the relationship between EAT, exercise capacity, and left ventricular structure and function. 

Sugita, K. Ito, S. Sakurai, et al., Epicardial adipose tissue is tightly associated with exercise intolerance in patients with type 2 diabetes mellitus with asymptomatic left ventricular structural  and functional abnormalities, Journal of Diabetes and Its Complications(2020)  https://doi.org/10.1016/j.jdiacomp.2020.107552 

George McConnell, PharmD. Candidate, LECOM School of Pharmacy