Insulin Resistance in Chronic Heart Failure: Relation to Severity and Etiology of Heart Failure

Swan, Jonathan W.; Anker, Stefan D.; Walton, Christopher; Godsland, Ian F.; Clark, Andrew L.; Leyva, Francisco; Stevenson, John C.; Coats, Andrew J.S.

doi:10.1016/s0735-1097(97)00185-x

Cited by 486 publications

(367 citation statements)

References 17 publications

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“…Although these metabolites represent a small portion of the human metabolome in terms of absolute numbers, they report on pathways critical for cellular and organism‐level homeostasis: fatty acid, carbohydrate, amino acid, and urea metabolism. These particular metabolites were chosen for several reasons: (1) An expanding body of evidence has implicated impairments in fatty acid and carbohydrate oxidation in HF pathophysiology, which could be reflected in acylcarnitine elevations13, 50, 73, 74, 75, 76, 77; (2) previous metabolomics investigations have identified derangements in plasma levels of these metabolites in HF patients49, 50, 78, 79, 80; and (3) acylcarnitines and their derivatives have been suggested to have intrinsic physiological effects that could contribute to the HF phenotype 66, 67, 68, 81, 82…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

201

137

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BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

201

137

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“…Low triiodotironine level contributes to the overall derangement of the neurohormonal control of circulation and recognizes a prognostic role [39]. CHF is associated with insulin resistance, characterized by both fasting and stimulated hyperinsulinaemia, which may induce altered metabolism of skeletal and heart muscle [40].…”

Section: The Hormonal Changesmentioning

confidence: 99%

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part I

Piepoli

Guazzi

Boriani

et al. 2010

European Journal of Cardiovascular Prevention & Rehabilitat

113

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Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. In this study, divided in two parts (see part II: pp. 643-648), we aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in symptom generation. In this first part of the review, six key factors are revised: the heart, the lung, the skeletal muscle, the hormonal changes, the O 2 delivery to the periphery, the endothelium. In the second part, the role of the excitatory reflexes and the cardiac cachexia will be presented, and finally, the potential therapeutic implications are discussed. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.

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“…Effects of insulin on protein metabolism in skeletal muscle and the liver are believed to be important in regulating the substrate availability for the heart (9). Insulin resistance is associated with increased risk of chronic heart failure (10). Insulin action through AKT signaling is also responsible for physiological heart growth during postnatal development (11).…”

Section: Introductionmentioning

confidence: 99%

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR−/− (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARα and PPARβ/δ in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARγ and PPARα did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.

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Insulin Resistance in Chronic Heart Failure: Relation to Severity and Etiology of Heart Failure

Cited by 486 publications

References 17 publications

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part I

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

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