Stress hyperglycemia: an essential survival response!

Paul E Marik, Rinaldo Bellomo, Paul E Marik, Rinaldo Bellomo

Abstract

Stress hyperglycemia is common in critically ill patients and appears to be a marker of disease severity. Furthermore, both the admission as well as the mean glucose level during the hospital stay is strongly associated with patient outcomes. Clinicians, researchers and policy makers have assumed this association to be causal with the widespread adoption of protocols and programs for tight in-hospital glycemic control. However, a critical appraisal of the literature has demonstrated that attempts at tight glycemic control in both ICU and non-ICU patients do not improve health care outcomes. We suggest that hyperglycemia and insulin resistance in the setting of acute illness is an evolutionarily preserved adaptive responsive that increases the host's chances of survival. Furthermore, attempts to interfere with this exceedingly complex multi-system adaptive response may be harmful. This paper reviews the pathophysiology of stress hyperglycemia and insulin resistance and the protective role of stress hyperglycemia during acute illness.

Figures

Figure 1
Figure 1
The neuroendocrine response to stress is characterized by gluconeogenesis and glycogenolysis resulting in stress hyperglycemia providing the immune system and brain with a ready source of fuel. ACTH, adrenocorticotrophic hormone; CRH, corticotrophin releasing hormone; LC/NE, locus ceruleus norepinephrine system; PVN, paraventricular nucleus.
Figure 2
Figure 2
Postulated interaction between the insulin signaling pathway and activation of the pro-inflammatory cascade in the pathogenesis of insulin resistance in sepsis. GLUT, glucose transporter; IκB, inhibitor κB; IKK, inhibitor κB kinase; IRS-1, insulin receptor substrate-1; LBP, lipopolysaccharide binding protein; LPS, lipopolysaccharide; NF-κB, nuclear factor-kappa B; NO, nitric oxide; TLR4, Toll-like receptor-4.
Figure 3
Figure 3
Variability of the basal and stress cortisol level amongst various animal species[16]. Dom. cat, domestic cat; R monkey, rhesus.

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