Stress-Induced Hyperglycaemia in Non-Diabetic Patients with Acute Coronary Syndrome: From Molecular Mechanisms to New Therapeutic Perspectives.

Alessandro Bellis,Antonio Cittadini,Ciro Mauro,Carmine Morisco,Emanuele Barbato,Antonio Ceriello

doi:10.3390/ijms22020775

Abstract

Stress-induced hyperglycaemia (SIH) at hospital admission for acute coronary syndrome is associated with poor outcome, especially in patients without known diabetes. Nevertheless, insulin treatment in these subjects was not correlated with the reduction of mortality. This is likely due to the fact that SIH in the context of an acute coronary syndrome, compared to that in known diabetes, represents an epiphenomenon of other pathological conditions, such as adrenergic and renin-angiotensin system over-activity, hyperglucagonaemia, increase of circulating free fatty acids and pancreatic beta-cell dysfunction, which are not completely reversed by insulin therapy and so worsen the prognosis. Thus, SIH may be considered not only as a biomarker of organ damage, but also as an indicator of a more complex therapeutic strategy in these subjects. The aim of this review is to analyse the molecular mechanisms by which SIH may favour a worse prognosis in non-diabetic patients with acute coronary syndrome and identify new therapeutic strategies, in addition to insulin therapy, for a more appropriate treatment and improved outcomes.

Highlights

Stress-induced hyperglycaemia (SIH) is a severe and very common condition where blood glucose levels >140 mg/dL (7.78 mmol/L) occur during hospitalisation for critical diseases [1]
Insulin exerts a lot of potential benefits on ischemic myocardium: (a) anti-inflammatory action, through the inhibition of the activity of nuclear factor-kB (NF-kB) and reduction of major chemotactic protein (ICAM-1) and C-reactive protein (CRP); (b) antithrombotic action, mediated by the inhibition of tissue factor (TF) and plasminogen activator inhibitor; (c) vasodilator effects, through platelet inhibition and increase in nitric oxide (NO) and cyclic AMP release; (d) glucose lowering action; (e) anti-apoptotic effects; and (f) anti-oxidant effects, mediated by inhibition of nitric oxide synthase (NOS) activity and consequent reduction of NO- free radicals production [80]
randomized clinical trials (RCTs) evaluating the effects of SIH pharmacological treatment in acute coronary syndrome (ACS) patient can be divided into two groups: (1) studies comparing a tighter glycaemic control versus standard therapy (Table 1); and (2) studies testing the effects on outcome of the glucose-insulinpotassium (GIK) versus standard therapy, independently on obtained glycaemic values (Table 2)

Summary

Introduction

Stress-induced hyperglycaemia (SIH) is a severe and very common condition where blood glucose levels >140 mg/dL (7.78 mmol/L) occur during hospitalisation for critical diseases [1]. Capes et al suggested some explanations to justify the worse outcome of hyperglycaemic non-diabetic patients compared to hyperglycaemic diabetic patients [4] These authors highlighted that it is difficult to precisely define SIH in diabetic subjects, because it is complex to establish their basal glycaemic values. They underlined that diabetic patients may have more CV risk factors, and, for this reason, SIH and long-term glucometabolic dysregulation may have a minor impact They remarked that a patient with known diabetes is more likely to receive insulin therapy, almost two-thirds of the patients hospitalised for ACS with hyperglycaemia at admission showed impaired glucose tolerance (IGT) or a newly diagnosed diabetes at three months after discharge [7,8]

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