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 Mesotten, D. Articles by van den Berghe, G. Search for Related Content PubMed PubMed Citation Articles by Mesotten, D. Articles by van den Berghe, G.

Regulation of Insulin-Like Growth Factor Binding Protein-1 during Protracted Critical Illness

Department of Intensive Care Medicine (D.M., F.W., G.V.d.B.) and Laboratory for Experimental Medicine and Endocrinology (F.V.), University Hospital Gasthuisberg, Catholic University Leuven, B-3000 Leuven, Belgium; and Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital (D.M., P.J.D.D., K.V.H., R.C.B.), St. Leonards, New South Wales 2065, Australia

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

Abstract

IGF binding protein-1 (IGFBP-1), an important regulator of IGF bioavailability, has been shown to correlate with mortality in critically ill patients. In the liver, IGFBP-1 is transcriptionally repressed by insulin, and it is therefore a potential marker of hepatic insulin sensitivity. We have recently shown that, compared with conventional treatment, maintenance of normoglycemia with intensive insulin therapy decreased morbidity and mortality of continuously fed critically ill patients. This study compares the effect of conventional and intensive insulin therapy on IGFBP-1 and assesses its predictive value for mortality.

In 363 patients who were dependent on intensive care for more than 7 d and were randomly assigned to either conventional or intensive insulin therapy, serum IGFBP-1 levels were measured on admission, on d 1, 8, 15, 22, and 29, and on the day of intensive care unit discharge or death. In addition, IGFBP-1 and phosphoenolpyruvate carboxykinase mRNA levels were measured by real-time RT-PCR in postmortem liver biopsies obtained from 74 patients who died in the intensive care unit.

Although intensive insulin treatment lowered glycemia, it had no effect on IGFBP-1 serum levels. Instead, serum IGFBP-1 concentration was significantly higher in patients who ultimately died, and it differentiated nonsurvivors from survivors 3 wk before death. The predictive value of serum IGFBP-1 for mortality was similar to that of the APACHE-II score. Like circulating IGFBP-1, hepatic mRNA levels of IGFBP-1 and the similarly insulin-regulated gene, phosphoenolpyruvate carboxykinase, were not significantly different between conventional and intensive insulin therapy groups.

These data suggest that hepatic insulin resistance in prolonged critically ill patients, reflected by high serum IGFBP-1 levels, is not overcome by intensive insulin therapy, and that this may affect patient outcome.

This article has been cited by other articles:

				B. Ellger, M. C. Richir, P. A. M. van Leeuwen, Y. Debaveye, L. Langouche, I. Vanhorebeek, T. Teerlink, and G. Van den Berghe Glycemic Control Modulates Arginine and Asymmetrical-Dimethylarginine Levels during Critical Illness by Preserving Dimethylarginine-Dimethylaminohydrolase Activity Endocrinology, June 1, 2008; 149(6): 3148 - 3157. [Abstract] [Full Text] [PDF]

				S B Catrina, R Rotarus, I R Botusan, M Coculescu, and K Brismar Desmopressin increases IGF-binding protein-1 in humans. Eur. J. Endocrinol., April 1, 2008; 158(4): 479 - 482. [Abstract] [Full Text] [PDF]

				B. Collier, L. A. Dossett, A. K. May, and J. J. Diaz Glucose Control and the Inflammatory Response Nutr Clin Pract, February 1, 2008; 23(1): 3 - 15. [Abstract] [Full Text] [PDF]

				M. Wallander, A. Norhammar, K. Malmberg, J. Ohrvik, L. Ryden, and K. Brismar IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes Diabetes Care, September 1, 2007; 30(9): 2343 - 2348. [Abstract] [Full Text] [PDF]

				M. P. Sperandeo, P. Annunziata, A. Bozzato, P. Piccolo, L. Maiuri, M. D'Armiento, A. Ballabio, G. Corso, G. Andria, G. Borsani, et al. Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance Am J Physiol Cell Physiol, July 1, 2007; 293(1): C191 - C198. [Abstract] [Full Text] [PDF]

				L. Langouche, I. Vanhorebeek, and G. Van den Berghe Glycaemic control in trauma patients, is there a role? Trauma, January 1, 2006; 8(1): 13 - 19. [Abstract] [PDF]

				R. P. Peeters, P. J. Wouters, H. van Toor, E. Kaptein, T. J. Visser, and G. Van den Berghe Serum 3,3',5'-Triiodothyronine (rT3) and 3,5,3'-Triiodothyronine/rT3 Are Prognostic Markers in Critically Ill Patients and Are Associated with Postmortem Tissue Deiodinase Activities J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4559 - 4565. [Abstract] [Full Text] [PDF]

				S. Basi, L. B. Pupim, E. M. Simmons, M. T. Sezer, Y. Shyr, S. Freedman, G. M. Chertow, R. L. Mehta, E. Paganini, J. Himmelfarb, et al. Insulin resistance in critically ill patients with acute renal failure Am J Physiol Renal Physiol, August 1, 2005; 289(2): F259 - F264. [Abstract] [Full Text] [PDF]

				A. Thorell, O. Rooyackers, P. Myrenfors, M. Soop, J. Nygren, and O. H. Ljungqvist Intensive Insulin Treatment in Critically Ill Trauma Patients Normalizes Glucose by Reducing Endogenous Glucose Production J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5382 - 5386. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Inpatient Diabetes Control: Rationale Diabetes Care, August 1, 2004; 27(8): 2074 - 2080. [Full Text] [PDF]

				D. Mesotten, P. J. Wouters, R. P. Peeters, K. V. Hardman, J. M. Holly, R. C. Baxter, and G. Van den Berghe Regulation of the Somatotropic Axis by Intensive Insulin Therapy during Protracted Critical Illness J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3105 - 3113. [Abstract] [Full Text] [PDF]

				D. Mesotten, J. V. Swinnen, F. Vanderhoydonc, P. J. Wouters, and G. Van den Berghe Contribution of Circulating Lipids to the Improved Outcome of Critical Illness by Glycemic Control with Intensive Insulin Therapy J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 219 - 226. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Aspects of Blood Pressure, Lipid, and Glycemic Treatment Diabetes Care, January 1, 2004; 27(1): 264 - 269. [Full Text] [PDF]