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Published in: Critical Care 3/2009

Open Access 01-06-2009 | Research

Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients

Authors: Alexander Koch, Olav A Gressner, Edouard Sanson, Frank Tacke, Christian Trautwein

Published in: Critical Care | Issue 3/2009

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Abstract

Introduction

Blood glucose levels and insulin resistance in critically ill patients on admission to intensive care units (ICUs) have been identified as factors influencing mortality. The pathogenesis of insulin resistance (IR) in critically ill patients is complex and not fully understood. Resistin is a hormone mainly derived from macrophages in humans and from adipose tissue in rodents, which regulates glucose metabolism and insulin sensitivity. In non-critically ill patients, resistin was found to be related to impaired glucose tolerance, insulin resistance, metabolic syndrome, obesity and type 2 diabetes. Therefore, resistin might represent a link between inflammation, acute phase response and insulin resistance in critically ill patients. We aimed to examine the correlation of serum resistin concentrations to parameters of inflammation, organ function, metabolism, disease severity and survival in critically ill patients.

Methods

On admission to the Medical ICU, 170 patients (122 with sepsis, 48 without sepsis) were studied prospectively and compared with 60 healthy non-diabetic controls. Clinical data, various laboratory parameters, metabolic and endocrine functions as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately three years.

Results

Resistin serum concentrations were significantly elevated in all critical care patients compared with healthy controls, and significantly higher in sepsis than in non-sepsis patients. Serum resistin concentrations were not associated with pre-existing type 2 diabetes or obesity. For all critically ill patients, a correlation to the homeostasis model assessment index of insulin resistance (HOMA-IR) was shown. Serum resistin concentrations were closely correlated to inflammatory parameters such as C-reactive protein, leukocytes, procalcitonin, and cytokines such as IL6 and TNF-α, as well as associated with renal failure and liver synthesis capacity. High resistin levels (> 10 ng/ml) were associated with an unfavourable outcome in non-sepsis patients on ICU and the overall survival.

Conclusions

Serum resistin concentrations are elevated in acute inflammation due to sepsis or systemic inflammatory response syndrome (SIRS). The close correlation with other acute phase proteins suggests a predominant, clinically relevant resistin release from macrophages in ICU patients. Moreover, resistin could potentially serve as a prognostic biomarker in non-sepsis critically ill patients.
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Literature
1.
go back to reference Van Cromphaut SJ, Vanhorebeek I, Berghe G: Glucose metabolism and insulin resistance in sepsis. Curr Pharm Des 2008, 14: 1887-1899. 10.2174/138161208784980563CrossRefPubMed Van Cromphaut SJ, Vanhorebeek I, Berghe G: Glucose metabolism and insulin resistance in sepsis. Curr Pharm Des 2008, 14: 1887-1899. 10.2174/138161208784980563CrossRefPubMed
2.
go back to reference Whitcomb BW, Pradhan EK, Pittas AG, Roghmann MC, Perencevich EN: Impact of admission hyperglycemia on hospital mortality in various intensive care unit populations. Crit Care Med 2005, 33: 2772-2777. 10.1097/01.CCM.0000189741.44071.25CrossRefPubMed Whitcomb BW, Pradhan EK, Pittas AG, Roghmann MC, Perencevich EN: Impact of admission hyperglycemia on hospital mortality in various intensive care unit populations. Crit Care Med 2005, 33: 2772-2777. 10.1097/01.CCM.0000189741.44071.25CrossRefPubMed
3.
go back to reference Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001, 345: 1359-1367. 10.1056/NEJMoa011300CrossRefPubMed Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001, 345: 1359-1367. 10.1056/NEJMoa011300CrossRefPubMed
4.
go back to reference Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354: 449-461. 10.1056/NEJMoa052521CrossRefPubMed Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354: 449-461. 10.1056/NEJMoa052521CrossRefPubMed
5.
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
6.
go back to reference Badman MK, Flier JS: The adipocyte as an active participant in energy balance and metabolism. Gastroenterology 2007, 132: 2103-2115. 10.1053/j.gastro.2007.03.058CrossRefPubMed Badman MK, Flier JS: The adipocyte as an active participant in energy balance and metabolism. Gastroenterology 2007, 132: 2103-2115. 10.1053/j.gastro.2007.03.058CrossRefPubMed
7.
go back to reference Dandona P, Aljada A, Bandyopadhyay A: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 2004, 25: 4-7. 10.1016/j.it.2003.10.013CrossRefPubMed Dandona P, Aljada A, Bandyopadhyay A: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 2004, 25: 4-7. 10.1016/j.it.2003.10.013CrossRefPubMed
8.
go back to reference Qatanani M, Lazar MA: Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev 2007, 21: 1443-1455. 10.1101/gad.1550907CrossRefPubMed Qatanani M, Lazar MA: Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev 2007, 21: 1443-1455. 10.1101/gad.1550907CrossRefPubMed
9.
go back to reference Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ: Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med 2007, 35: 1536-1542. 10.1097/01.CCM.0000266536.14736.03CrossRefPubMed Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ: Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med 2007, 35: 1536-1542. 10.1097/01.CCM.0000266536.14736.03CrossRefPubMed
10.
go back to reference Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001, 409: 307-312. 10.1038/35053000CrossRefPubMed Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 2001, 409: 307-312. 10.1038/35053000CrossRefPubMed
11.
go back to reference Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA: Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003, 300: 472-476. 10.1016/S0006-291X(02)02841-3CrossRefPubMed Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA: Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003, 300: 472-476. 10.1016/S0006-291X(02)02841-3CrossRefPubMed
12.
go back to reference Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S: Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001, 50: 2199-2202. 10.2337/diabetes.50.10.2199CrossRefPubMed Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S: Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001, 50: 2199-2202. 10.2337/diabetes.50.10.2199CrossRefPubMed
13.
go back to reference Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV: Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003, 88: 5452-5455. 10.1210/jc.2002-021808CrossRefPubMed Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV: Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003, 88: 5452-5455. 10.1210/jc.2002-021808CrossRefPubMed
14.
go back to reference McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S: Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 2003, 88: 6098-6106. 10.1210/jc.2003-030898CrossRefPubMed McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S: Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 2003, 88: 6098-6106. 10.1210/jc.2003-030898CrossRefPubMed
15.
go back to reference Youn BS, Yu KY, Park HJ, Lee NS, Min SS, Youn MY, Cho YM, Park YJ, Kim SY, Lee HK, Park KS: Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004, 89: 150-156. 10.1210/jc.2003-031121CrossRefPubMed Youn BS, Yu KY, Park HJ, Lee NS, Min SS, Youn MY, Cho YM, Park YJ, Kim SY, Lee HK, Park KS: Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004, 89: 150-156. 10.1210/jc.2003-031121CrossRefPubMed
16.
go back to reference Qatanani M, Szwergold NR, Greaves DR, Ahima RS, Lazar MA: Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest 2009, in press. Qatanani M, Szwergold NR, Greaves DR, Ahima RS, Lazar MA: Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest 2009, in press.
17.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644CrossRefPubMed
18.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13: 818-829. 10.1097/00003246-198510000-00009CrossRefPubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13: 818-829. 10.1097/00003246-198510000-00009CrossRefPubMed
19.
go back to reference Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F: Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4. Diabetes Care 2007, 30: 1168-1172. 10.2337/dc06-2323CrossRefPubMed Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F: Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4. Diabetes Care 2007, 30: 1168-1172. 10.2337/dc06-2323CrossRefPubMed
20.
go back to reference McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S: Resistin, central obesity, and type 2 diabetes. Lancet 2002, 359: 46-47. 10.1016/S0140-6736(02)07281-1CrossRefPubMed McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S: Resistin, central obesity, and type 2 diabetes. Lancet 2002, 359: 46-47. 10.1016/S0140-6736(02)07281-1CrossRefPubMed
21.
go back to reference Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE: Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002, 87: 978-982. 10.1210/jc.87.3.978CrossRefPubMed Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE: Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002, 87: 978-982. 10.1210/jc.87.3.978CrossRefPubMed
22.
go back to reference Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A: Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 2004, 27: 2450-2457. 10.2337/diacare.27.10.2450CrossRefPubMed Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A: Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 2004, 27: 2450-2457. 10.2337/diacare.27.10.2450CrossRefPubMed
23.
go back to reference Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ: Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005, 111: 932-939. 10.1161/01.CIR.0000155620.10387.43CrossRefPubMed Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ: Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005, 111: 932-939. 10.1161/01.CIR.0000155620.10387.43CrossRefPubMed
24.
go back to reference Al-Daghri N, Chetty R, McTernan PG, Al-Rubean K, Al-Attas O, Jones AF, Kumar S: Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population. Cardiovasc Diabetol 2005, 4: 10. 10.1186/1475-2840-4-10PubMedCentralCrossRefPubMed Al-Daghri N, Chetty R, McTernan PG, Al-Rubean K, Al-Attas O, Jones AF, Kumar S: Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population. Cardiovasc Diabetol 2005, 4: 10. 10.1186/1475-2840-4-10PubMedCentralCrossRefPubMed
25.
go back to reference Bo S, Gambino R, Pagani A, Guidi S, Gentile L, Cassader M, Pagano GF: Relationships between human serum resistin, inflammatory markers and insulin resistance. Int J Obes (Lond) 2005, 29: 1315-1320. 10.1038/sj.ijo.0803037CrossRef Bo S, Gambino R, Pagani A, Guidi S, Gentile L, Cassader M, Pagano GF: Relationships between human serum resistin, inflammatory markers and insulin resistance. Int J Obes (Lond) 2005, 29: 1315-1320. 10.1038/sj.ijo.0803037CrossRef
26.
go back to reference Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003, 149: 331-335. 10.1530/eje.0.1490331CrossRefPubMed Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003, 149: 331-335. 10.1530/eje.0.1490331CrossRefPubMed
27.
go back to reference Fujinami A, Obayashi H, Ohta K, Ichimura T, Nishimura M, Matsui H, Kawahara Y, Yamazaki M, Ogata M, Hasegawa G, Nakamura N, Yoshikawa T, Nakano K, Ohta M: Enzyme-linked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 2004, 339: 57-63. 10.1016/j.cccn.2003.09.009CrossRefPubMed Fujinami A, Obayashi H, Ohta K, Ichimura T, Nishimura M, Matsui H, Kawahara Y, Yamazaki M, Ogata M, Hasegawa G, Nakamura N, Yoshikawa T, Nakano K, Ohta M: Enzyme-linked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 2004, 339: 57-63. 10.1016/j.cccn.2003.09.009CrossRefPubMed
28.
go back to reference Pfutzner A, Langenfeld M, Kunt T, Lobig M, Forst T: Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance. Clin Lab 2003, 49: 571-576.PubMed Pfutzner A, Langenfeld M, Kunt T, Lobig M, Forst T: Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance. Clin Lab 2003, 49: 571-576.PubMed
29.
go back to reference Stejskal D, Adamovska S, Bartek J, Jurakova R, Proskova J: Resistin – concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003, 147: 63-69.CrossRefPubMed Stejskal D, Adamovska S, Bartek J, Jurakova R, Proskova J: Resistin – concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003, 147: 63-69.CrossRefPubMed
30.
go back to reference Yang J, Li M, Wu CY, Wang H, Xu QS, Deng JY: Reduced resistin levels in patients with type 2 diabetes mellitus. Zhonghua Yi Xue Za Zhi 2003, 83: 1471-1474.PubMed Yang J, Li M, Wu CY, Wang H, Xu QS, Deng JY: Reduced resistin levels in patients with type 2 diabetes mellitus. Zhonghua Yi Xue Za Zhi 2003, 83: 1471-1474.PubMed
31.
go back to reference Axelsson J, Bergsten A, Qureshi AR, Heimburger O, Barany P, Lonnqvist F, Lindholm B, Nordfors L, Alvestrand A, Stenvinkel P: Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int 2006, 69: 596-604. 10.1038/sj.ki.5000089CrossRefPubMed Axelsson J, Bergsten A, Qureshi AR, Heimburger O, Barany P, Lonnqvist F, Lindholm B, Nordfors L, Alvestrand A, Stenvinkel P: Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int 2006, 69: 596-604. 10.1038/sj.ki.5000089CrossRefPubMed
32.
go back to reference Yagmur E, Trautwein C, Gressner AM, Tacke F: Resistin serum levels are associated with insulin resistance, disease severity, clinical complications, and prognosis in patients with chronic liver diseases. Am J Gastroenterol 2006, 101: 1244-1252. 10.1111/j.1572-0241.2006.00543.xCrossRefPubMed Yagmur E, Trautwein C, Gressner AM, Tacke F: Resistin serum levels are associated with insulin resistance, disease severity, clinical complications, and prognosis in patients with chronic liver diseases. Am J Gastroenterol 2006, 101: 1244-1252. 10.1111/j.1572-0241.2006.00543.xCrossRefPubMed
Metadata
Title
Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients
Authors
Alexander Koch
Olav A Gressner
Edouard Sanson
Frank Tacke
Christian Trautwein
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7925

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