Response to exercise training and outcomes in patients with heart failure and diabetes mellitus: insights from the HF-ACTION trial
Open accessAbstract
Background In HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), exercise training improved functional capacity in heart failure with reduced ejection fraction (HFrEF). Previous studies have suggested that diabetes mellitus (DM) may be associated with an attenuated response to exercise. We explored whether DM attenuated the improvement in functional capacity with exercise.Methods and results HF-ACTION randomized 2331 patients with HFrEF to medical therapy with or without exercise training over a median follow-up of 2.5 years. We examined the interaction between DM and exercise response measured by change in 6-minute walk distance (6MWD) and peak VO2. We also examined outcomes by DM status. In HF-ACTION, 748 (32%) patients had DM. DM patients had lower functional capacity at baseline and had lower exercise volumes at 3 months. There was a significant interaction between DM status and exercise training for change in peak VO2 (interaction P = .02), but not 6MWD. In the exercise arm, DM patients had a smaller mean increase in peak VO2 than non-DM patients (P = .03). There was no interaction between DM and exercise on clinical outcomes. After risk adjustment, DM was associated with increased all-cause mortality/hospitalization (P = .03).Conclusions In HF-ACTION, DM was associated with lower baseline functional capacity, an attenuated improvement in peak VO2, and increased hospitalizations.
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The coexistence of type 2 diabetes mellitus and heart failure, either with reduced or preserved ejection fraction, is frequent, affecting 30-40% of patients.
“The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients)”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
The highest prevalence of T2DM was seen in trials of acute HF, around 40%.
“The highest prevalence of T2DM was seen in trials of acute HF (around 40%).”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype.
“In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype (i.e.HFrEF and HFpEF) (Table 3).31 -48”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
Patients with T2DM and both HFrEF and HFpEF have worse NYHA functional class and more HF-related symptoms and signs than patients without T2DM, despite having similar ejection fraction.
“Patients with T2DM and both HFrEF 1,34,69,70 and HFpEF 1 have worse NYHA functional class and more HF-related symptoms and signs than patients without T2DM, despite having similar ejection fraction.69,70”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
Clinical trial results are somewhat conflicting regarding the risk of all-cause and cardiovascular mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF.
“Clinical trial results are somewhat conflicting regarding the risk of all-cause and CV mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF (Table 5).1,31 -35,37,40,42,44,45,69,88-92”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
The HF-ACTION trial enrolled 32% of patients with T2DM and there was no interaction between T2DM status and the effect of exercise on clinical outcomes.
“The trial enrolled 32% of patients with T2DM and there was no interaction between T2DM status and the effect of exercise on clinical outcomes.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
In an adjusted analysis, exercise training led to an 11% (P=0.03) reduction in the primary composite outcome of all-cause mortality or all-cause hospitalization.
“In an adjusted analysis, exercise training led to an 11% (P=0.03)reduction in the primary composite outcome of all-cause mortality or all-cause hospitalization.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [34]
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Truby, L. K., Regan, J. A., Giamberardino, S. N., Ilkayeva, O., Bain, J., Newgard, C. B., O’Connor, C. M., Felker, G. M., Kraus, W. E., McGarrah, R. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15102687
Self-citationTruby, L. K., Regan, J. A., Giamberardino, S. N., Ilkayeva, O., Bain, J., Newgard, C. B., O’Connor, C. M., Felker, G. M., Kraus, W. E., McGarrah, R. W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15102693
Self-citationSugita, Y., Kudo, A., Arakawa, S., & Sakai, S. (2025) · Heart and Vessels · doi:10.1007/s00380-025-02645-0
Vieira, J. M., Carvalho, V. O., Aguiar, L. A., Smart, N. A., Monteiro, C. N., Weege, M. H., da Silva, R. P., RANGEL, B., & Gomes-Neto, M. (2026) · Clinical Rehabilitation · doi:10.1177/02692155261416862
Evolution of Exercise Training in Patients with Pulmonary Hypertension—A Comprehensive Review
Beis, I., Δίπλα, Κ., Boutou, A., Zacharias, A., Pataka, A., Sourla, E., Zafeiridis, A., & Pitsiou, G. (2026) · Healthcare · doi:10.3390/healthcare14121796
- Authors
- Banks, A. Z., Mentz, R. J., Stebbins, A., Mikus, C. R., Schulte, P. J., Fleg, J. L., Cooper, L. S., Leifer, E. S., Badenhop, D. T., Keteyian, S. J., Piña, I. L., Kitzman, D. W., Fiuzat, M., Whellan, D. J., Kraus, W. E., & O'Connor, C. M.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- National Heart, Lung, and Blood Institute (US)
- University of Toledo Medical Center (US)
- Henry Ford Hospital (US)
- Albert Einstein College of Medicine (US)
- Wake Forest University Health Sciences (US)
- Thomas Jefferson University (US)
- Corresponding author
- Banks, Adam Z.
- ORCID
- Venue
- Journal of Cardiac Failure
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 22
- Issue
- 7
- Pages
- 485-491
- ISSN
- 1071-9164 (ISSN-L)
- PMC
- PMC4903090
- OpenAlex
- W2193380125
- Cited by
- 56
- References
- 28
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 4
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cardiac Failure (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL063747)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- heart failure with reduced ejection fraction, diabetes mellitus, exercise training, functional capacity, peak oxygen uptake, 6-minute walk distance, HF-ACTION trial, all-cause mortality, hospitalization
- MeSH terms
- Aged, Diabetes Mellitus, Exercise Therapy, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Patient Compliance, Treatment Outcome, Exercise Tolerance
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