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Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology
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 facil...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113493/ https://www.ncbi.nlm.nih.gov/pubmed/31863644 http://dx.doi.org/10.1002/jcsm.12515 |
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author | Garnham, Jack O. Roberts, Lee D. Espino‐Gonzalez, Ever Whitehead, Anna Swoboda, Peter P. Koshy, Aaron Gierula, John Paton, Maria F. Cubbon, Richard M. Kearney, Mark T. Egginton, Stuart Bowen, T. Scott Witte, Klaus K. |
author_facet | Garnham, Jack O. Roberts, Lee D. Espino‐Gonzalez, Ever Whitehead, Anna Swoboda, Peter P. Koshy, Aaron Gierula, John Paton, Maria F. Cubbon, Richard M. Kearney, Mark T. Egginton, Stuart Bowen, T. Scott Witte, Klaus K. |
author_sort | Garnham, Jack O. |
collection | PubMed |
description | 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: Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R (2) = 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. |
format | Online Article Text |
id | pubmed-7113493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71134932020-04-02 Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology Garnham, Jack O. Roberts, Lee D. Espino‐Gonzalez, Ever Whitehead, Anna Swoboda, Peter P. Koshy, Aaron Gierula, John Paton, Maria F. Cubbon, Richard M. Kearney, Mark T. Egginton, Stuart Bowen, T. Scott Witte, Klaus K. J Cachexia Sarcopenia Muscle Original Articles 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: Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R (2) = 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. John Wiley and Sons Inc. 2019-12-21 2020-04 /pmc/articles/PMC7113493/ /pubmed/31863644 http://dx.doi.org/10.1002/jcsm.12515 Text en © 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Garnham, Jack O. Roberts, Lee D. Espino‐Gonzalez, Ever Whitehead, Anna Swoboda, Peter P. Koshy, Aaron Gierula, John Paton, Maria F. Cubbon, Richard M. Kearney, Mark T. Egginton, Stuart Bowen, T. Scott Witte, Klaus K. Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title | Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title_full | Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title_fullStr | Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title_full_unstemmed | Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title_short | Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
title_sort | chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113493/ https://www.ncbi.nlm.nih.gov/pubmed/31863644 http://dx.doi.org/10.1002/jcsm.12515 |
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