Reporting on Glucose Control Metrics in the Intensive Care Unit

European Endocrinology, 2015;11(2):75–8 DOI:


The ‘diabetes of injury’ typically associated with critical illness has recently been thoroughly revisited and much better characterised following major therapeutic advances. The occurrence of severe hyperglycaemia, moderate hypoglycaemia or high glycaemic variability has been associated with an increased mortality and rate of complications in large independent cohorts of acutely ill patients. Hence, current guidelines advocate the prevention and avoidance of each of these three dysglycaemic domains, and the use of a common metrics for a quantitative description of dysglycaemic events, such as the proportion of time spent in the target glycaemic range as a unifying variable. Using a common language will help to face the future challenges, including the definition of the most appropriate blood glucose (BG) target according to the category of admission, the time interval from the initial injury and the medical history. The clinical testing of technological improvements in the monitoring systems and the therapeutic algorithms should be assessed using the same metrics.
Keywords: Critically ill, stress hyperglycaemia, diabetes of injury, stress response, insulin, blood glucose, continuous glucose monitoring (CGM)
Disclosure: Rafael Machado Tironi and Jean-Charles Preiser have no conflicts of interest to declare. No funding was received for the publication of this article.
Received: June 17, 2015 Accepted July 16, 2015
Correspondence: Jean-Charles Preiser, Department of Intensive Care, Erasme University Hospital, Universite libre de Bruxelles, 808 route de Lennik, B-1070 Brussels, Belgium. E:
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Acute illness is typically associated with the so-called ‘stress-induced hyperglycaemia’, defined as a transient hyperglycaemia in patients without previous evidence of diabetes.1 The strong relationship between stress hyperglycaemia and poor outcome is largely established and actually validates hyperglycaemia as a marker of illness severity.

The correction of a moderate stress hyperglycaemia may improve the prognosis. Indeed, in 2001, a large single-centre randomised controlled trial (RCT) in critically ill surgical patients demonstrated that tight glucose control (TGC) (defined as the restoration and maintenance of blood glucose [BG] concentration between 4.4 and 6.1 mmol/l [80 and 110 mg/l]) by intensive insulin therapy (IIT) was associated with decreased mortality and rate of complications.2 However, subsequent studies performed in other intensive care units (ICUs)3–8 failed to reproduce the beneficial effects of IIT titrated to achieve TGC.9 The controversy that followed these conflicting results triggered a major interest in the physiopathology of stress response, resulting in important findings and a re-appraisal of the current knowledge.

This review intends to provide a brief summary of the current understanding of the toxicity of prolonged hyperglycaemia, the mechanisms underlying the three domains of dysglycaemia, that is, hyperglycaemia, hypoglycaemia and high glycaemic variability (GV), and the available clinical data from observational and interventional studies, and to outline some of the challenges for the future of the field.

Prolonged Hyperglycaemia-associated Toxicity

In stress conditions, an overall massive glucose overload happens in organs where glucose uptake is not regulated by insulin, usually quoted as non-insulin-mediated glucose uptake (NIMGU) tissues, under the influence of pro-inflammatory mediators, counterregulatory hormones, and hypoxia.10 Hence, a wide range of tissues, including hepatocytes, endothelial cells, neurons, nephrons and immune cells, may be susceptible to enhanced glucose toxicity as a result of acute illness. Several deleterious effects have been associated with these high glucose concentrations in cells.1,11 Damage to mitochondrial proteins occurs and the formation of reactive oxygen species (ROS) is increased as a consequence of the shift from glycolysis towards accessory metabolic pathways (pentose phosphate, hexosamines, polyols).12 Other effects of excess glucose concentrations include the exacerbation of inflammatory pathways, decreased complement activity, modifications in the innate immune system, impairment in endothelial and hepatic mitochondrial functions and abolishment of the ischaemic preconditioning and protein glycosylation. Acute complications attributed to stress hyperglycaemia include renal failure, increased susceptibility to infections, polyneuropathy and impaired microcirculation.1

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Keywords: Critically ill, stress hyperglycaemia, diabetes of injury, stress response, insulin, blood glucose, continuous glucose monitoring (CGM)