Insulin resistance in heart failure: differences between patients with reduced and preserved left ventricular ejection fraction

Abstract

Aims Insulin resistance (IR) is a characteristic feature of heart failure (HF) pathophysiology that affects symptoms and mortality. Differences in the pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not characterized in detail. The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF. Methods and results We included 18 patients with HFrEF (EF 30 ± 11%, body mass index (BMI) 26.5 ± 3.3 kg/m2), 22 HFpEF patients (EF 63 ± 7%, BMI 28.6 ± 4.8 kg/m2), and 20 healthy controls of similar age, all without diabetes mellitus. Patients were in stable ambulatory condition and on stable medical regimens for HF. IR was assessed at fasting steady state by the homeostasis model assessment (HOMA) index and within the physiological range of insulin–glucose interactions by the short insulin sensitivity test (SIST). Fasting‐state IR was observed in HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range (IQR) 1.5–3.6 vs. HOMA 3.1, IQR 1.4–3.7 vs. controls 1.2, IQR 1.8–0.9, respectively; analysis of variance P < 0.001), but no statistical difference was observed between HFpEF and HFrEF. The dynamic test over the physiological range of insulin–glucose interactions revealed a more severe IR in HFrEF as compared with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64–89) mg/dL) at the end of the SIST compared with HFpEF and controls (68 (58–79) and 56 (44–66) mg/dL, respectively, P < 0.001). Conclusion IR is present in non‐diabetic patients with HFpEF and HFrEF. However, distinct differences in the insulin sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced testing. Patients with HFrEF showed more severe IR.

Cardiac cachexia: hic et nunc

“…The major anabolic hormones modulating protein metabolism in skeletal muscle include insulin, growth hormone (GH), and insulin‐like growth factor 1 (IGF‐1) . It has been previously proved that insulin resistance may play an important role in skeletal muscle dysfunction in HF . Since IGF‐1 has been shown to stimulate protein synthesis and to reduce protein degradation, changes in the GH/IGF‐1 axis may impact the anabolic/catabolic balance in the wasting syndrome .…”

“…16 It has been previously proved that insulin resistance may play an important role in skeletal muscle dysfunction in HF. 20,26 Since IGF-1 has been shown to stimulate protein synthesis and to reduce protein degradation, changes in the GH/IGF-1 axis may impact the anabolic/catabolic balance in the wasting syndrome. 27 Patients with HF-related systolic or diastolic dysfunction have significantly lower plasma levels of total IGF-1, but free IGF-1 is significantly higher than in healthy controls.…”

Heart–brain interactions in patients with heart failure, including takotsubo syndrome: a need to monitor autonomic sympathetic activity: reply

“…3 Yet, acceptable quantitative assessment of insulin sensitivity is limited to elaborate methods such as clamp techniques or intravenous glucose tolerance testing that are unsuitable for clinical and widespread use. 4 A simple and robust method to quantify insulin sensitivity would be of high value in the emerging field of metabolic tailored treatments in HF. 5 Other examples of insufficient assessment options in everyday clinical work are endothelium function or immune activation.…”

Insulin resistance in heart failure: widening the divide between reduced and preserved ejection fraction?

“…In this issue of the journal, Scherbakov et al provide incremental insights into the correlation between IR and HF . The investigators examined fasting and dynamic measures of IR separately in patients with stable ambulatory HFrEF and HFpEF without diabetes.…”