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Reporting on Glucose Control Metrics in the Intensive Care Unit
Rafael Machado Tironi 1 and Jean-Charles Preiser 2
1. Registrar; 2. Professor, Department of Intensive Care, Erasme University Hospital, Universite libre de Bruxelles, Brussels, Belgium
Abstract 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.
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.
Received: 17 June 2015 Accepted: 16 July 2015 Citation: European Endocrinology, 2015;11(2):75–8
Correspondence: Jean-Charles Preiser, Department of Intensive Care, Erasme University Hospital, Universite libre de Bruxelles, 808 route de Lennik, B-1070 Brussels,
Belgium. E: firstname.lastname@example.org
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
Tou ch MEd ica l MEdia
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
Mechanisms Underlying the Three
Domains of Dysglycaemia
Hyperglycaemia Although sharing some similarities, the pathogenetic mechanisms of
type 2 diabetes and stress hyperglycaemia are different (see Table 1).
In diabetes, the cause of hyperglycaemia is a combination of insulin
resistance and defective secretion of insulin by pancreatic β-cells. During
stress hyperglycaemia, complex interactions between counterregulatory
hormones (catecholamines, growth hormone, cortisol) and cytokines
lead to an excessive and non-inhibitable production of glucose