The Association of Heart Failure With Insulin Resistance and the Development of Type 2 Diabetes

Kostis, John B.; Sanders, Michael

doi:10.1016/j.amjhyper.2004.11.038

Cited by 84 publications

(72 citation statements)

References 65 publications

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“…Impaired blood flow further increases levels of adrenaline (epinephrine) and noradrenaline (norepinephrine). This neurohumoral compensating mechanism has been suggested to increase insulin resistance and hepatic gluconeogenesis as well as decrease the release of insulin from the pancreatic beta cells [16]. Sympathetic nervous system overactivity has also been shown to acutely reduce insulin sensitivity, but the role of development of overt diabetes remains to be established [5,17,18].…”

Section: Discussionmentioning

confidence: 99%

Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study

et al. 2014

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Aims/hypothesis Heart failure has been suggested to increase the risk of developing diabetes. We investigated the relation between heart failure severity, defined by loop-diuretic dosage, and the risk of developing diabetes in a nationwide cohort of patients with heart failure. Methods We followed all Danish patients discharged from hospitalisation for first-time heart failure in 1997-2010, without prior use of hypoglycaemic agents, until a claimed prescription for hypoglycaemic agents, death or 31 December 2010. The association of loop-diuretic dosage (furosemide equivalents) 90 days after discharge (study baseline) with risk of diabetes was estimated by multivariate Cox regression models.Results In total, 99,362 patients were included and divided into five loop-diuretic dose groups: 30,838 (31%) used no loop diuretics; 24,389 (25%) used >0-40 mg/day; 17,355 (17%) used >40-80 mg/day; 11,973 (12%) used >80-159 mg/day; and 14,807 (15%) used ≥160 mg/day. A total of 7,958 patients (8%) developed diabetes. Loop-diuretic dosages were associated with an increased risk of developing diabetes in a dose-dependent manner. Concomitant use of renin-angiotensin system inhibitors (RASis) attenuated the risk (p value for interaction <0.0001). Compared with patients using no loop diuretics (group 1), the adjusted HRs (95% CI) for developing diabetes for groups 2-5 respectively were 1.16

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Section: Discussionmentioning

confidence: 99%

Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study

et al. 2014

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“…treatment of diabetes and its implications constitutes a major health care expenditure (19). A significant proportion of diabetic patients are known to develop diabetic cardiomyopathy, with a high incidence of congestive heart failure (33).…”

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confidence: 99%

Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium

DeNicola

Wang

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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. Two weeks later, cardiac function was assessed by echocardiography and an isovolumetrically perfused heart. Compared with control MI hearts, stimulation of GLP-1R improved cardiac function, which was associated with attenuation of myocardial hypertrophy, the mitigation of interstitial fibrosis, and an increase in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were preconditioned with exendin-4 at a dose of 100 nmol/l and then subjected to hydrogen peroxide exposure at concentrations of 50 and 100 mol/l. The exendin-4 treatment decreased lactate dehydrogenase leakage and increased cell survival. Notably, this event was also associated with the reduction of cleaved caspase-3 and caspase-9 and attenuation of reactive oxygen species production. Exendin-4 treatments improved mitochondrial respiration and suppressed the opening of mitochondrial permeability transition pore and protected mitochondria function. Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection and mitigating oxidative stress-induced injury.glucagon-like peptide-1 receptor; exendin-4; heart; infarction; oxidant stress

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“…19 T2DM predisposes severe presentations of HF and predicts HF mortality; Ϸ25% of stable compared with Ͼ33% of patients with decompensated HF manifest T2DM. 20,21 In 1187 men prospectively assessed over 9 years, IR predicted the development of HF. One standard deviation decrease in insulin sensitivity increased the risk of HF by approximately one third.…”

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confidence: 99%

Metabolic Mechanisms in Heart Failure

Ashrafian

Frenneaux

Opie³

2007

Circulation

462

301

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Abstract-Although neurohumoral antagonism has successfully reduced heart failure morbidity and mortality, the residual disability and death rate remains unacceptably high. Though abnormalities of myocardial metabolism are associated with heart failure, recent data suggest that heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation. A detrimental self-perpetuating cycle (heart failure 3 altered metabolism 3 heart failure) that promotes the progression of heart failure may thus be postulated. Accordingly, we review the cellular mechanisms and pathophysiology of altered metabolism and insulin resistance in heart failure. It is hypothesized that the ensuing detrimental myocardial energetic perturbations result from neurohumoral activation, increased adverse free fatty acid metabolism, decreased protective glucose metabolism, and in some cases insulin resistance. The result is depletion of myocardial ATP, phosphocreatine, and creatine kinase with decreased efficiency of mechanical work. On the basis of the mechanisms outlined, appropriate therapies to mitigate aberrant metabolism include intense neurohumoral antagonism, limitation of diuretics, correction of hypokalemia, exercise, and diet. We also discuss more novel mechanistic-based therapies to ameliorate metabolism and insulin resistance in heart failure. For example, metabolic modulators may optimize myocardial substrate utilization to improve cardiac function and exercise performance beyond standard care. The ultimate success of metabolic-based therapy will be manifest by its capacity further to lessen the residual mortality in heart failure. Key Words: fatty acids Ⅲ glucose Ⅲ heart failure Ⅲ insulin resistance D espite significant therapeutic advances, heart failure (HF) remains a leading cause of morbidity and mortality in developed 1 and increasingly in developing countries, 2 with a 5-year mortality rate of Ϸ50%, which rivals or exceeds that of many cancers. 3 This unacceptably high residual mortality and morbidity has mandated a reevaluation of cardiac biology with the aim to identify novel therapeutic strategies for HF. Because the daily turnover of ATP (Ϸ6 to 35 kg) is very many times that of the myocardial ATP pool, and even the healthy heart only extracts Ϸ25% of energy derivable from substrates, 4 it is not surprising that even subtle variations in the efficiency of energy generation or utilization may have a profound cumulative impact on cellular energy levels. 5 Thus cardiac energetics in particular and metabolism in general represent promising targets for HF therapy. 6 Correspondingly, numerous studies have identified decreased cardiac energy levels and flux as a consistent feature of HF. 6,7 These observations have been reinforced by genomic studies 8 and have focused considerable attention on metabolic modulation as a therapy for HF. 6 Specifically, altered myocardial carbohydrate metabolism and the related state of myocardial insulin resistance (IR), in which given concentrations of...

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The Association of Heart Failure With Insulin Resistance and the Development of Type 2 Diabetes

Cited by 84 publications

References 65 publications

Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study

Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study

Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium

Metabolic Mechanisms in Heart Failure

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