Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology

Abstract

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.

Malondialdehyde as a Useful Biomarker of Low Hand Grip Strength in Community-Dwelling Stroke Patients

“…In our study, stroke patients had significantly decreased SOD activity levels with a concomitant increase in CAT activity compared with that of controls. Exhaustion may decrease serum SOD activity following prolonged ROS generation during ischemic events [50] and skeletal muscle pathology [51]. A previous study suggested that increased plasma SOD activity occurs after dynamic resistance training in post-stroke patients [48].…”

Prioritizing symptom management in the treatment of chronic heart failure

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Quantifying the relationship and contribution of mitochondrial respiration to systemic exercise limitation in heart failure

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“…The patients included in this study are a subset of those on whom we have previously published other outcomes. [30][31][32] Cardiopulmonary exercise test Cardiopulmonary exercise testing data for patients were obtained from a peak symptom-limited CPET conducted as part of routine clinical care, continued to volitional intolerance on a cycle ergometer for determination of V O 2peak , V O 2LT , peak circulatory power (CircP peak ), and peak oxygen (O 2 ) pulse, RER peak , and V E/V CO 2LT . After a 5-min warm-up at 10 W, the patients started cycling at 20 W and workload was progressively increased by 5 W min À1 until the patients reached volitional intolerance.…”