This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langouche, L. Articles by Van den Berghe, G. Search for Related Content PubMed PubMed Citation Articles by Langouche, L. Articles by Van den Berghe, G. Related Collections Diabetes and Insulin

Effect of Intensive Insulin Therapy on Insulin Sensitivity in the Critically Ill

Departments of Intensive Care Medicine (L.L., S.V.P., P.J.W., G.V.d.B.) and Abdominal Surgery (A.D.), Katholieke Universiteit Leuven, B-3000, Leuven, Belgium; and Medical Department M (Endocrinology and Diabetes) (T.K.H.), Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Greet Van den Berghe, M.D., Ph.D., Department of Intensive Care Medicine, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium. E-mail: greet.vandenberghe{at}med.kuleuven.be.

Context: Hyperglycemia and hyperinsulinemia are common in intensive care unit (ICU) patients and relate to illness severity. Intensive insulin therapy (IIT) to maintain normoglycemia reduces morbidity and mortality. Blood glucose control explains this benefit because a high insulin dose is associated with adverse outcome. Mitogenic insulin effects could theoretically explain this link.

Objective: To investigate further the association between insulin dose and adverse outcome, we studied the effect of IIT on circulating insulin levels, markers of insulin sensitivity, and the metabolic and mitogenic insulin signaling molecules in key tissues.

Design: This is a subanalysis of a large randomized, controlled study.

Setting: The study was performed in a university hospital surgical ICU.

Patients: A total of 339 critically ill patients, treated in ICU for at least a week, were included in this subanalysis.

Intervention: Strict normoglycemia with IIT compared with conventional insulin therapy was performed.

Results: Severalfold higher insulin doses than with conventional insulin therapy were required to maintain normoglycemia with IIT. However, serum insulin levels were only transiently higher with IIT, despite the much lower blood glucose levels. IIT normalized the elevated serum C-peptide levels and increased circulating adiponectin levels. The metabolic insulin signal was increased by IIT in muscle, but not in liver. The mitogenic insulin signal in either tissue was not affected by IIT.

Conclusions: Normoglycemia can be maintained in ICU patients without a sustained further elevation of insulinemia. Together with the increased adiponectin levels, this finding suggests that IIT may improve insulin sensitivity. Skeletal muscle, but not liver, revealed an increased metabolic insulin signal. The therapy did not impose mitogenic risk in these tissues.

This article has been cited by other articles:

				P. Dandona, A. Chaudhuri, H. Ghanim, and P. Mohanty Insulin as an anti-inflammatory and antiatherogenic modulator. J. Am. Coll. Cardiol., February 3, 2009; 53(5 Suppl): S14 - S20. [Abstract] [Full Text] [PDF]