Insulin Protects the Endothelium in the Critically Ill

Intensive insulin therapy safeguards the endothelium of critically ill patients and improves survival.

Dr. Greet Van den Berghe, Senior investigator stated that the findings "point to one of two major pathways via which strict blood glucose control with insulin works to protect vital organs and how it improves survival of critical illness. By protecting the endothelium, the treatment is likely to improve perfusion of the organs and thus to protect supply of oxygen."

Dr. Van den Berghe of the Catholic University of Leuven and colleagues conducted a subanalysis of a randomized controlled study involving 224 critically ill patients given standard insulin therapy and another 181 who received intensive insulin therapy.
In total, 21% of the patients on standard therapy died in the intensive care unit versus 12% of those given intensive therapy. There were fewer intensive therapy patients with bacteremia and acute renal failure. They also spent less time on mechanical ventilation and had a shorter ICU stay.

Maintaining normoglycemia with intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels, reflecting reduced endothelial activation. This, say the investigators, is probably brought about in part by inhibition of excessive nitric oxide (NO) release by inducible NO synthase.

"We had previously shown," Dr. Van den Berghe added, "that intensive insulin therapy also protects the cells directly via protecting the mitochondria."

Protection of the mitochondria and the endothelium appears paramount in such patients in providing "better organ perfusion and better organ function," she continued. "No treatment in intensive care so far has shown to be so effective on these two crucial pathways."

She concluded: "Understanding how such a simple intervention exerts such powerful effects is very important to understand how we can further improve outcome of these sick patients in ICU."
J Clin Invest 2005;115:2277-2286.