WHY INSULIN SAVES LIVES IN THE ICU

Abstract

Introduction: Strict maintenance of normoglycaemia with intensive insulin therapy in the critically ill surgical patients has helped to reduce morbidity and mortality by almost 50%. The notion that insulin may act independently of glucose as an anti inflammatory agent is of interest. Orthopaedist manipulate the inflammatory cascade through the practice of Damage Control Surgery. By delaying surgery they prevent a second hit in the Systemic Inflammatory Response Syndrome (SIRS) and attenuate excessive inflammation which may lead to Multiorgan Failure (MOF). An insulin infusion is a novel method of modulating the inflammatory cascade through the strict control of hyperglycaemia.

The role of neutrophils and endothelium are an integral part of the inflammatory cascade. Our aim was to investigate whether insulin had an independent effect on endothelial cell activation.

Aim: We hypothesise that insulin, independent of glucose, has a cytoprotective effect on the endothelium as an anti inflammatory agent.

Methods: We subjected human umbilical vein endothelial cells (HUVEC) to normoxia, hypoxia and hypoxia reoxygenation to simulate trauma. These 3 groups were incubated with insulin at 0uU/ml, 10uU/ml, 50uU/ml and 100uU/ml for 24h and 48h normoxia and hypoxia. For the hypoxia reoxygenation study HUVEC were exposed to 24h of hypoxia and then 24h of reoxygenation. Proliferation of endothelial cells was measured using an MTT study.

Results: Our experiment shows that hypoxia reduces HUVEC proliferation. Results show that treatment with 50uU/ml insulin for 24 hours attenuates the effect of hypoxia. This suggests that insulin at post prandial, physiological levels, in non diabetics has a cytoprotective effect on endothelial cells. This was significant in hypoxic conditions in a dose dependent manner.

Conclusions: Hypoxia simulates injury and when injury occurs it activates an inflammatory response which could lead to SIRS. It has not previously been investigated how insulin acts as an anti inflammatory mediator in the control of hyperglycaemia. We can conclude that insulin may act to protect the endothelium, independent of glucose, under hypoxia and hypoxia reoxygenation conditions.