Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 6/2008

Open Access 01-12-2008 | Research

Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions

Authors: Michael Lehrke, Uli C Broedl, Ingeborg M Biller-Friedmann, Michael Vogeser, Volkmar Henschel, Kirsten Nassau, Burkhard Göke, Erich Kilger, Klaus G Parhofer

Published in: Critical Care | Issue 6/2008

Login to get access

Abstract

Introduction

Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation.

Methods

Insulin resistance was measured in a cohort of 37 non-diabetic patients undergoing cardiac surgery by assessment of insulin requirement to maintain euglycaemia and repeated measurements of an insulin glycaemic index. The kinetics of cortisol, interleukin 6 (IL6), tumour necrosis factor α (TNFα), resistin, leptin and adiponectin were assessed by repeated measurements in a period of 48 h.

Results

Insulin resistance increased during the observation period and peaked 22 h after the beginning of the operation. IL6 and TNFα displayed an early increase with peak concentrations at the 4-h time point. Serum levels of cortisol, resistin and leptin increased more slowly and peaked at the 22-h time point, while adiponectin declined, reaching a base at the 22-h time point. Model assessment identified cortisol as the best predictor of insulin resistance, followed by IL6, leptin and adiponectin. No additional information was gained by modelling for TNFα, resistin, catecholamine infusion rate, sex, age, body mass index (BMI), operation time or medication.

Conclusions

Serum cortisol levels are the best predictor for inflammatory insulin resistance followed by IL6, leptin and adiponectin. TNFα, and resistin have minor relevance as predictors of stress dependent insulin resistance.
Appendix
Available only for authorised users
Literature
1.
2.
Benomar Y, Wetzler S, Larue-Achagiotis C, Djiane J, Tome D, Taouis M: In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus. Mol Cell Endocrinol 2005, 242: 59-66. 10.1016/j.mce.2005.07.003CrossRefPubMed
3.
4.
Kremen J, Dolinkova M, Krajickova J, Blaha J, Anderlova K, Lacinova Z, Haluzikova D, Bosanska L, Vokurka M, Svacina S, Haluzik M: Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance. J Clin Endocrinol Metab 2006, 91: 4620-4627. 10.1210/jc.2006-1044CrossRefPubMed
5.
Anderson PD, Mehta NN, Wolfe ML, Hinkle CC, Pruscino L, Comiskey LL, Tabita-Martinez J, Sellers KF, Rickels MR, Ahima RS, Reilly MP: Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab 2007, 92: 2272-2279. 10.1210/jc.2006-2545CrossRefPubMed
6.
Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS: Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events. Circulation 2004, 109: 1497-1502. 10.1161/01.CIR.0000121747.71054.79CrossRefPubMed
7.
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
8.
Traynor C, Hall GM: Endocrine and metabolic changes during surgery: anaesthetic implications. Br J Anaesth 1981, 53: 153-160. 10.1093/bja/53.2.153CrossRefPubMed
9.
Jakob SM, Ensinger H, Takala J: Metabolic changes after cardiac surgery. Curr Opin Clin Nutr Metab Care 2001, 4: 149-155. 10.1097/00075197-200103000-00012CrossRefPubMed
10.
Lin B, Morris DW, Chou JY: Hepatocyte nuclear factor 1α is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids. DNA Cell Biol 1998, 17: 967-74.CrossRefPubMed
11.
Leboeuf B, Renold AE, Cahill GF Jr: Studies on rat adipose tissue in vitro. IX. Further effects cortisol on glucose metabolism. J Biol Chem 1962, 237: 988-991.PubMed
12.
Mooney RA: Counterpoint: interleukin-6 does not have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 2007, 102: 816-818. 10.1152/japplphysiol.01208a.2006CrossRefPubMed
13.
Pedersen BK, Febbraio MA: Point: interleukin-6 does have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 2007, 102: 814-816. 10.1152/japplphysiol.01208.2006CrossRefPubMed
14.
Muller 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-α or its receptors. Diabetologia 2002, 45: 805-812. 10.1007/s00125-002-0829-2CrossRefPubMed
15.
Pickup JC, Chusney GD, Thomas SM, Burt D: Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes. Life Sci 2000, 67: 291-300. 10.1016/S0024-3205(00)00622-6CrossRefPubMed
16.
Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001, 280: E745-751.PubMed
17.
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001, 286: 327-334. 10.1001/jama.286.3.327CrossRefPubMed
18.
Stith RD, Luo J: Endocrine and carbohydrate responses to interleukin-6 in vivo. Circ Shock 1994, 44: 210-215.PubMed
19.
Klover PJ, Zimmers TA, Koniaris LG, Mooney RA: Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 2003, 52: 2784-2789. 10.2337/diabetes.52.11.2784CrossRefPubMed
20.
Klover PJ, Clementi AH, Mooney RA: Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology 2005, 146: 3417-3427. 10.1210/en.2004-1468CrossRefPubMed
21.
Weigert C, Hennige AM, Lehmann R, Brodbeck K, Baumgartner F, Schauble M, Haring HU, Schleicher ED: Direct cross-talk of interleukin-6 and insulin signal transduction via insulin receptor substrate-1 in skeletal muscle cells. J Biol Chem 2006, 281: 7060-7067. 10.1074/jbc.M509782200CrossRefPubMed
22.
Krogh-Madsen R, Plomgaard P, Moller K, Mittendorfer B, Pedersen BK: Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans. Am J Physiol Endocrinol Metab 2006, 291: E108-E114. 10.1152/ajpendo.00471.2005CrossRefPubMed
23.
24.
Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A, Nicola NA, Alexander WS, Hilton DJ: Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA 1996, 93: 14564-14568. 10.1073/pnas.93.25.14564PubMedCentralCrossRefPubMed
25.
Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB: Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J Immunol 2002, 168: 4018-4024.CrossRefPubMed
26.
Ozata M, Ozdemir IC, Licinio J: Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999, 84: 3686-3895. 10.1210/jc.84.10.3686CrossRefPubMed
27.
Ceddia RB, Koistinen HA, Zierath JR, Sweeney G: Analysis of paradoxical observations on the association between leptin and insulin resistance. FASEB J 2002, 16: 1163-1176. 10.1096/fj.02-0158revCrossRefPubMed
28.
Sivitz WI, Walsh SA, Morgan DA, Thomas MJ, Haynes WG: Effects of leptin on insulin sensitivity in normal rats. Endocrinology 1997, 138: 3395-3401. 10.1210/en.138.8.3395PubMed
29.
Muzzin P, Eisensmith RC, Copeland KC, Woo SL: Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc Natl Acad Sci USA 1996, 93: 14804-14808. 10.1073/pnas.93.25.14804PubMedCentralCrossRefPubMed
30.
Zierath JR, Frevert EU, Ryder JW, Berggren PO, Kahn BB: Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes. Diabetes 1998, 47: 1-4. 10.2337/diabetes.47.1.1CrossRefPubMed
31.
32.
Howard JK, Flier JS: Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab 2006, 17: 365-371. 10.1016/j.tem.2006.09.007CrossRefPubMed
33.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001, 7: 941-946. 10.1038/90984CrossRefPubMed
34.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001, 86: 1930-1935. 10.1210/jc.86.5.1930CrossRefPubMed
35.
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
36.
Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA: An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 2004, 1: e45. 10.1371/journal.pmed.0010045PubMedCentralCrossRefPubMed
37.
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS: Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 1997, 389: 610-614. 10.1038/39335CrossRefPubMed
38.
Michie HR, Spriggs DR, Manogue KR, Sherman ML, Revhaug A, O'Dwyer ST, Arthur K, Dinarello CA, Cerami A, Wolff SM, et al.: Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery 1988, 104: 280-286.PubMed
39.
Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J, CORTICUS Study Group: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358: 111-124. 10.1056/NEJMoa071366CrossRefPubMed
Metadata
Title
Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions
Authors
Michael Lehrke
Uli C Broedl
Ingeborg M Biller-Friedmann
Michael Vogeser
Volkmar Henschel
Kirsten Nassau
Burkhard Göke
Erich Kilger
Klaus G Parhofer
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7152

Other articles of this Issue 6/2008

Critical Care 6/2008 Go to the issue

Research

Nitrogen washout/washin, helium dilution and computed tomography in the assessment of end expiratory lung volume

Research

Nurses' prediction of volume status after aneurysmal subarachnoid haemorrhage: a prospective cohort study

Research

Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study

Book report

Selladurai B, Reilly P: Initial Management of Head Injury: A Comprehensive Guide. McGraw-Hill Medical; 2007, 315 pages.

Review

Clinical review: Critical care management of spontaneous intracerebral hemorrhage

Research

Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis