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Organ dysfunction in critical illness: impact of maintaining normoglycemia and glycemia-independent insulin actions

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Critical Care200610 (Suppl 1) :P248

  • Published:


  • Acetylcholine
  • Glycemic Control
  • Organ Dysfunction
  • Critical Illness
  • Nitroprusside


Tight glycemic control by intensive insulin therapy (IIT) reduces mortality and risk of organ failure in critically ill patients. The relative impact of maintaining normoglycemia and of glycemia-independent actions of insulin in explaining these clinical benefits remains unknown.


In a TPN-fed rabbit model of prolonged (7 days) critical illness we assessed the impact of normoglycemia/normoinsulin-emia, normoglycemia/hyperinsulinemia, hyperglycemia/normoinsulin-emia and hyperglycemia/hyperinsulinemia on survival and organ function. Assessment of myocardial function (dp/dtmax) was performed under mechanical ventilation on day 7. Aortic rings were isolated to quantify endothelium-dependent relaxation by relaxation to cumulative doses of acetylcholine (Ach), Ach + L-nitro-arginine-methyl-ester and nitroprusside, respectively, of norepinephrine (NE)-induced vasoconstriction. Leukocyte function and plasma markers of kidney and liver function were measured.


Both normoglycemic groups revealed a mortality rate of 11%, whereas mortality was 36% in the HG/NI group and 47% in the HG/HI group (P = 0.03). Left ventricular contractility was increased by high insulin levels exclusively when normoglycemia was maintained (P < 0.05). The two normoglycemic groups revealed largely sustained endothelium-dependent vasorelaxation, as compared with both hyperglycemic groups (P < 0.05), independently of insulinemia. Nitroprusside-induced relaxation was not affected. Leukocyte function as well as kidney and liver function were protected only in both normoglycemic groups and deteriorated in both hyperglycemic groups (P < 0.05).


Survival benefits and prevention of organ dysfunction by IIT largely depend on glycemic control rather than on glycemia-independent actions of insulin. When normoglycemia is maintained, insulin might exert a glycemia-independent effect on myocardial contractility.

Authors’ Affiliations

Catholic University of Leuven, Belgium


© BioMed Central Ltd 2006