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Published in: Critical Care 2/2012

Open Access 01-04-2012 | Research

Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients

Authors: Masataka Nakamura, Shigeto Oda, Tomohito Sadahiro, Eizo Watanabe, Ryuzo Abe, Taka-aki Nakada, Yasumasa Morita, Hiroyuki Hirasawa

Published in: Critical Care | Issue 2/2012

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Abstract

Introduction

The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients.

Methods

This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia.

Results

A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P < 0.01). The rate of successful glucose control (blood glucose level < 150 mg/dl maintained for 6 days or longer) decreased with increase in blood IL-6 level on ICU admission (P < 0.01). The blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P < 0.01 and P < 0.01, respectively).

Conclusions

High blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.
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Literature
1.
go back to reference Capes SE, Hunt D, Malmberg K, Gerstein HC: Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000, 355: 773-778. 10.1016/S0140-6736(99)08415-9CrossRefPubMed Capes SE, Hunt D, Malmberg K, Gerstein HC: Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000, 355: 773-778. 10.1016/S0140-6736(99)08415-9CrossRefPubMed
2.
go back to reference Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC: Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001, 32: 2426-2432. 10.1161/hs1001.096194CrossRefPubMed Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC: Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001, 32: 2426-2432. 10.1161/hs1001.096194CrossRefPubMed
3.
go back to reference Rovlias A, Kotsou S: The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000, 46: 335-342. 10.1097/00006123-200002000-00015CrossRefPubMed Rovlias A, Kotsou S: The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000, 46: 335-342. 10.1097/00006123-200002000-00015CrossRefPubMed
4.
go back to reference Marik PE: Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med 2004, 30: 748-756. 10.1007/s00134-004-2167-yCrossRefPubMed Marik PE: Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med 2004, 30: 748-756. 10.1007/s00134-004-2167-yCrossRefPubMed
5.
go back to reference Van Cromphaut SJ, Vanhorebeek I, Van den Berghe G: Glucose metabolism and insulin resistance in sepsis. Curr Pharm Des 2008, 14: 1887-1899. 10.2174/138161208784980563CrossRefPubMed Van Cromphaut SJ, Vanhorebeek I, Van den Berghe G: Glucose metabolism and insulin resistance in sepsis. Curr Pharm Des 2008, 14: 1887-1899. 10.2174/138161208784980563CrossRefPubMed
6.
go back to reference Losser MR, Damoisel C, Payen D: Bench-to-bedside review: Glucose and stress conditions in the intensive care unit. Crit Care 2010, 14: 231. 10.1186/cc9100PubMedCentralCrossRefPubMed Losser MR, Damoisel C, Payen D: Bench-to-bedside review: Glucose and stress conditions in the intensive care unit. Crit Care 2010, 14: 231. 10.1186/cc9100PubMedCentralCrossRefPubMed
7.
go back to reference Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 2004, 30: 536-555. 10.1007/s00134-004-2210-zCrossRefPubMed Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 2004, 30: 536-555. 10.1007/s00134-004-2210-zCrossRefPubMed
8.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 34: 17-60. 10.1007/s00134-007-0934-2PubMedCentralCrossRefPubMed Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 34: 17-60. 10.1007/s00134-007-0934-2PubMedCentralCrossRefPubMed
10.
go back to reference Gustot T: Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care 2011, 17: 153-159. 10.1097/MCC.0b013e328344b446CrossRefPubMed Gustot T: Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care 2011, 17: 153-159. 10.1097/MCC.0b013e328344b446CrossRefPubMed
11.
go back to reference Abraham E, Mervyn S: Mechanisms of sepsis-induced organ dysfunction. Crit Care Med 2007, 35: 2408-2416. 10.1097/01.CCM.0000282072.56245.91CrossRefPubMed Abraham E, Mervyn S: Mechanisms of sepsis-induced organ dysfunction. Crit Care Med 2007, 35: 2408-2416. 10.1097/01.CCM.0000282072.56245.91CrossRefPubMed
12.
go back to reference Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamura M: Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005, 29: 169-175. 10.1016/j.cyto.2004.10.010CrossRefPubMed Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamura M: Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005, 29: 169-175. 10.1016/j.cyto.2004.10.010CrossRefPubMed
13.
go back to reference Abe R, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Tateishi Y, Shinozaki K, Hirasawa H: Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care 2010, 14: R27. 10.1186/cc8898PubMedCentralCrossRefPubMed Abe R, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Tateishi Y, Shinozaki K, Hirasawa H: Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care 2010, 14: R27. 10.1186/cc8898PubMedCentralCrossRefPubMed
14.
go back to reference Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC, GenIMS Investigators: Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med 2007, 167: 1655-1663. 10.1001/archinte.167.15.1655PubMedCentralCrossRefPubMed Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC, GenIMS Investigators: Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med 2007, 167: 1655-1663. 10.1001/archinte.167.15.1655PubMedCentralCrossRefPubMed
15.
go back to reference Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M: Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care 2011, 26: 54-64. 10.1016/j.jcrc.2010.04.011CrossRefPubMed Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M: Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care 2011, 26: 54-64. 10.1016/j.jcrc.2010.04.011CrossRefPubMed
16.
go back to reference Gregoric P, Sijacki A, Stankovic S, Radenkovic D, Ivancevic N, Karamarkovic A, Popovic N, Karadzic B, Stijak L, Stefanovic B, Milosevic Z, Bajec D: SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors. Hepatogastroenterology 2010, 57: 349-353.PubMed Gregoric P, Sijacki A, Stankovic S, Radenkovic D, Ivancevic N, Karamarkovic A, Popovic N, Karadzic B, Stijak L, Stefanovic B, Milosevic Z, Bajec D: SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors. Hepatogastroenterology 2010, 57: 349-353.PubMed
17.
go back to reference American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20: 864-874. 10.1097/00003246-199206000-00025CrossRef American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20: 864-874. 10.1097/00003246-199206000-00025CrossRef
18.
go back to reference Grimble RF: Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002, 5: 551-559. 10.1097/00075197-200209000-00015CrossRefPubMed Grimble RF: Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002, 5: 551-559. 10.1097/00075197-200209000-00015CrossRefPubMed
19.
go back to reference Petit F, Bagby GJ, Lang CH: Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance. Am J Physiol 1995, 268: E219-E228.PubMed Petit F, Bagby GJ, Lang CH: Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance. Am J Physiol 1995, 268: E219-E228.PubMed
20.
go back to reference Rotter V, Nagaev I, Smith U: Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003, 278: 45777-45784. 10.1074/jbc.M301977200CrossRefPubMed Rotter V, Nagaev I, Smith U: Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003, 278: 45777-45784. 10.1074/jbc.M301977200CrossRefPubMed
21.
go back to reference Müller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, Haastert B, Giani G, Illig T, Thorand B, Kolb H: Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 2002, 45: 805-812. 10.1007/s00125-002-0829-2CrossRefPubMed Müller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, Haastert B, Giani G, Illig T, Thorand B, Kolb H: Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 2002, 45: 805-812. 10.1007/s00125-002-0829-2CrossRefPubMed
22.
go back to reference Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, Yano Y: Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998, 83: 859-862. 10.1210/jc.83.3.859PubMed Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, Yano Y: Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998, 83: 859-862. 10.1210/jc.83.3.859PubMed
23.
go back to reference Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358: 125-139. 10.1056/NEJMoa070716CrossRefPubMed Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358: 125-139. 10.1056/NEJMoa070716CrossRefPubMed
24.
go back to reference NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009, 360: 1283-1297.CrossRef NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009, 360: 1283-1297.CrossRef
25.
go back to reference Eslami S, Abu-Hanna A, de Keizer NF, Bosman RJ, Spronk PE, de Jonge E, Schultz MJ: Implementing glucose control in intensive care: a multicenter trial using statistical process control. Intensive Care Med 2010, 36: 1556-1565. 10.1007/s00134-010-1924-3PubMedCentralCrossRefPubMed Eslami S, Abu-Hanna A, de Keizer NF, Bosman RJ, Spronk PE, de Jonge E, Schultz MJ: Implementing glucose control in intensive care: a multicenter trial using statistical process control. Intensive Care Med 2010, 36: 1556-1565. 10.1007/s00134-010-1924-3PubMedCentralCrossRefPubMed
26.
go back to reference Meyfroidt G, Wouters P, De Becker W, Cottem D, Van den Berghe G: Impact of a computer-generated alert system on the quality of tight glycemic control. Intensive Care Med 2011, 37: 1151-1157. 10.1007/s00134-011-2159-7CrossRefPubMed Meyfroidt G, Wouters P, De Becker W, Cottem D, Van den Berghe G: Impact of a computer-generated alert system on the quality of tight glycemic control. Intensive Care Med 2011, 37: 1151-1157. 10.1007/s00134-011-2159-7CrossRefPubMed
27.
go back to reference Hanazaki K, Maeda H, Okabayashi T: Tight perioperative glycemic control using an artificial endocrine pancreas. Surg Today 2010, 40: 1-7. 10.1007/s00595-009-4061-2CrossRefPubMed Hanazaki K, Maeda H, Okabayashi T: Tight perioperative glycemic control using an artificial endocrine pancreas. Surg Today 2010, 40: 1-7. 10.1007/s00595-009-4061-2CrossRefPubMed
29.
go back to reference Nakamura M, Oda S, Sadahiro T, Hirayama Y, Watanabe E, Tateishi Y, Nakada TA, Hirasawa H: Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator. Contrib Nephrol 2010, 166: 73-82.CrossRefPubMed Nakamura M, Oda S, Sadahiro T, Hirayama Y, Watanabe E, Tateishi Y, Nakada TA, Hirasawa H: Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator. Contrib Nephrol 2010, 166: 73-82.CrossRefPubMed
Metadata
Title
Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients
Authors
Masataka Nakamura
Shigeto Oda
Tomohito Sadahiro
Eizo Watanabe
Ryuzo Abe
Taka-aki Nakada
Yasumasa Morita
Hiroyuki Hirasawa
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2012
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc11301

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