Key result
Diabetic heart failure linked to severe skeletal muscle pathology including mitochondrial impairment and fibre atrophy.
Why the study?
Patients with coexistent CHF and DM have greater exercise limitation and worse prognosis than those without DM even when corrected for cardiac dysfunction, but the origins of these symptoms remain poorly understood.
What are the specific skeletal muscle pathological changes in patients with coexistent chronic heart failure and diabetes mellitus compared to those with either condition alone or healthy controls?
Observational (n=115)
What are the specific skeletal muscle pathological changes in patients with coexistent chronic heart failure and diabetes mellitus compared to those with either condition alone or healthy controls?
p-value: p=<0.05
Patients with diabetic heart failure exhibit a distinct and severe skeletal muscle pathology characterized by mitochondrial dysfunction, fibre atrophy, and reduced capillarity, which may contribute to their exercise intolerance.
Muscle pathology may underlie exercise intolerance in diabetic HF; hypothesis-generating and requires prospective trials before clinical adoption.
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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Garnham et al. (2019) conducted an observational in Chronic heart failure with diabetes mellitus (n=115). Diabetic heart failure (exposure) vs. Age-matched controls, DM alone, and CHF alone was evaluated on Skeletal muscle phenotype (mitochondrial function, reactive oxygen species, fibre morphology, capillarity, and gene expression) (p=<0.05). Diabetic heart failure was associated with severe skeletal muscle pathology, including mitochondrial impairments, higher reactive oxygen species (P<0.05), and severe fibre atrophy (P<0.05).
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