Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology
Open accessAbstract
BACKGROUND: Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D-HF). METHODS: In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age-matched controls (n = 25), DM (n = 10), CHF (n = 52), and D-HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole-body exercise capacity. RESULTS: = 0.64; P < 0.001). Mitochondrial impairments in D-HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti-oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D-HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). CONCLUSIONS: Patients with D-HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D-HF.
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Exercise intolerance is due to a combination of central factors such as heart rate and stroke volume as well as peripheral factors including skeletal muscle structure and function.
“Exercise intolerance is due to a combination of central factors such as heart rate and stroke volume as well as peripheral factors including skeletal muscle structure and function (Figure 2 ), 32 , 33 , 34”
From Prioritizing symptom management in the treatment of chronic heart failure (2020) · cites this paper as [34]
The Introduction and Discussion link skeletal muscle structure and mitochondrial function to exercise limitation in patients with chronic heart failure, particularly those with diabetes. The paper does not establish the claimed combination with central factors such as heart rate and stroke volume; its Limitations section also says the observational findings cannot prove causality. No page numbers are available in our copy. (LLM, conf=0.86)
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- Authors
- Garnham, J. O., Roberts, L. D., Espino‐Gonzalez, E., Whitehead, A., Swoboda, P. P., Koshy, A., Gierula, J., Paton, M. F., Cubbon, R. M., Kearney, M. T., Egginton, S., Bowen, T. S., & Witte, K. K.
- Affiliations
- University of Leeds (GB)
- School of Biomedical Sciences, Faculty of Biological Sciences University of Leeds Leeds UK
- Corresponding author
- Bowen, T. Scott
- ORCID
- Venue
- Journal of Cachexia Sarcopenia and Muscle
- Publisher
- Wiley
- Published
- 2019-12-21
- Volume
- 11
- Issue
- 2
- Pages
- 394-404
- ISSN
- 2190-5991 (ISSN-L)
- 2190-6009
- PMC
- PMC7113493
- OpenAlex
- W2995199017
- Cited by
- 32
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 1
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation Leducq (TNE 13CVD04)
- British Heart Foundation (PG/14/15/30691)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- diabetic heart failure, chronic heart failure, diabetes mellitus, skeletal muscle pathology, exercise intolerance, mitochondrial dysfunction, reactive oxygen species, manganese superoxide dismutase, NDUFS1, capillarity, pectoralis major, muscle biopsy, exercise capacity
- MeSH terms
- Aged, Chronic Disease, Female, Heart Failure, Humans, Male, Muscle, Skeletal, Diabetes Complications
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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