Inpatient initiation of sodium-glucose cotransporter-2 inhibitors: the prescribing learning curve.

We aimed to describe the safety and tolerability of initiation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) during hospitalisation with heart failure, and the frequency of, and reasons for, subsequent discontinuation. In total, 934 patients who were not already prescribed a SGLT2i were hospitalised with heart failure, 77 (8%) were initiated on a SGLT2i a median of five (3-8.5) days after admission and two (0.

Reduction of heart failure guideline-directed medication during hospitalization: prevalence, risk factors, and outcomes.

Aims: Optimal management of heart failure with reduced ejection fraction (HFrEF) includes titration of guideline-directed medical therapy (GDMT) to the highest tolerated dose within the licensed range. During hospitalization, GDMT doses are often significantly altered, although it is unknown whether the cause of hospitalization influences this.

Methods And Results: We recruited 711 people with stable HFrEF from specialist heart failure clinics and prospectively assessed events occurring during first unplanned hospitalization.

Novel Paracrine Action of Endothelium Enhances Glucose Uptake in Muscle and Fat.

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Association of heart failure and its comorbidities with loss of life expectancy.

Objective: Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy.

Methods: We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals.

Nox2 NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction.

Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin resistance (endothelial specific and whole body). Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat.

The IGF-1 receptor and regulation of nitric oxide bioavailability and insulin signalling in the endothelium.

The insulin-like growth factor-1 receptor (IGF-1R), like the insulin receptor (IR), plays a significant role in determining bioavailability of the critical signalling molecule nitric oxide (NO) and hence, modulates endothelial cell function, particularly in response to stimulation with insulin. In particular, the ability of the IGF-1R to form hybrid receptors with the IR appears to be highly significant in determining the sensitivity of the endothelial cell to insulin. This review will examine the structure of the IGF-1R and how this, with particular reference to the ability of the IGF-1R and the IR to form hybrid receptors, may have an effect both on endothelial cell function and the development of cardiovascular disease.

Novel role of the IGF-1 receptor in endothelial function and repair: studies in endothelium-targeted IGF-1 receptor transgenic mice.

We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bioavailability and endothelial cell insulin sensitivity. In the present report, we aimed to examine the effect of increasing IGF-1R on endothelial cell function and repair. To examine the effect of increasing IGF-1R in the endothelium, we generated mice overexpressing human IGF-1R in the endothelium (human IGF-1R endothelium-overexpressing mice [hIGFREO]) under direction of the Tie2 promoter enhancer.

The role of IGF-1 resistance in obesity and type 2 diabetes-mellitus-related insulin resistance and vascular disease.

Importance Of The Field: The insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity are a major cause of cardiovascular disease on a global scale. These disorders are not only a cause of ill health but are a huge financial drain on healthcare systems. T2DM leads to an increased risk of cardiovascular mortality equivalent to over 10 years of ageing while obesity independent of T2DM also leads to a substantially increased risk of acute myocardial infarction.