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Published in: Critical Care 4/2010

Open Access 01-08-2010 | Research

The use of exenatide in severely burned pediatric patients

Authors: Gabriel A Mecott, David N Herndon, Gabriela A Kulp, Natasha C Brooks, Ahmed M Al-Mousawi, Robert Kraft, Haidy G Rivero, Felicia N Williams, Ludwik K Branski, Marc G Jeschke

Published in: Critical Care | Issue 4/2010

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Abstract

Introduction

Intensive insulin treatment (IIT) has been shown to improve outcomes post-burn in severely burnt patients. However, it increases the incidence of hypoglycemia and is associated with risks and complications. We hypothesized that exenatide would decrease plasma glucose levels post-burn to levels similar to those achieved with IIT, and reduce the amount of exogenous insulin administered.

Methods

This open-label study included 24 severely burned pediatric patients. Six were randomized to receive exenatide, and 18 received IIT during acute hospitalization (block randomization). Exenatide and insulin were administered to maintain glucose levels between 80 and 140 mg/dl. We determined 6 AM, daily average, maximum and minimum glucose levels. Variability was determined using mean amplitude of glucose excursions (MAGE) and percentage of coefficient of variability. The amount of administered insulin was compared in both groups.

Results

Glucose values and variability were similar in both groups: Daily average was 130 ± 28 mg/dl in the intervention group and 138 ± 25 mg/dl in the control group (P = 0.31), MAGE 41 ± 6 vs. 45 ± 12 (respectively). However, administered insulin was significantly lower in the exenatide group than in the IIT group: 22 ± 14 IU patients/day in the intervention group and 76 ± 11 IU patients/day in the control group (P = 0.01). The incidence rate of hypoglycemia was similar in both groups (0.38 events/patient-month).

Conclusions

Patients receiving exenatide received significantly lower amounts of exogenous insulin to control plasma glucose levels. Exenatide was well tolerated and potentially represents a novel agent to attenuate hyperglycemia in the critical care setting.

Trial registration

NCT00673309.
Appendix
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Literature
1.
go back to reference Gore DC, Chinkes D, Heggers J, Herndon DN, Wolf SE, Desai M: Association of hyperglycemia with increased mortality after severe burn injury. J Trauma 2001, 51: 540-544. 10.1097/00005373-200109000-00021CrossRefPubMed Gore DC, Chinkes D, Heggers J, Herndon DN, Wolf SE, Desai M: Association of hyperglycemia with increased mortality after severe burn injury. J Trauma 2001, 51: 540-544. 10.1097/00005373-200109000-00021CrossRefPubMed
2.
go back to reference Gore DC, Chinkes DL, Hart DW, Wolf SE, Herndon DN, Sanford AP: Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients. Crit Care Med 2002, 30: 2438-2442. 10.1097/00003246-200211000-00006CrossRefPubMed Gore DC, Chinkes DL, Hart DW, Wolf SE, Herndon DN, Sanford AP: Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients. Crit Care Med 2002, 30: 2438-2442. 10.1097/00003246-200211000-00006CrossRefPubMed
3.
go back to reference Hemmila MR, Taddonio MA, Arbabi S, Maggio PM, Wahl WL: Intensive insulin therapy is associated with reduced infectious complications in burn patients. Surgery 2008, 144: 629-637. 10.1016/j.surg.2008.07.001PubMedCentralCrossRefPubMed Hemmila MR, Taddonio MA, Arbabi S, Maggio PM, Wahl WL: Intensive insulin therapy is associated with reduced infectious complications in burn patients. Surgery 2008, 144: 629-637. 10.1016/j.surg.2008.07.001PubMedCentralCrossRefPubMed
4.
go back to reference Pham TN, Warren AJ, Phan HH, Molitor F, Greenhalgh DG, Palmieri TL: Impact of tight glycemic control in severely burned children. J Trauma 2005, 59: 1148-1154. 10.1097/01.ta.0000188933.16637.68CrossRefPubMed Pham TN, Warren AJ, Phan HH, Molitor F, Greenhalgh DG, Palmieri TL: Impact of tight glycemic control in severely burned children. J Trauma 2005, 59: 1148-1154. 10.1097/01.ta.0000188933.16637.68CrossRefPubMed
5.
go back to reference Jeschke MG, Kulp GA, Kraft R, Finnerty CC, Mlcak R, Lee JO, Herndon DN: Intensive insulin therapy in severely burned pediatric patients: A prospective randomized trial. Am J Respir Crit Care Med 2010, in press. Jeschke MG, Kulp GA, Kraft R, Finnerty CC, Mlcak R, Lee JO, Herndon DN: Intensive insulin therapy in severely burned pediatric patients: A prospective randomized trial. Am J Respir Crit Care Med 2010, in press.
6.
go back to reference Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert 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. 10.1056/NEJMoa0810625CrossRefPubMed Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert 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. 10.1056/NEJMoa0810625CrossRefPubMed
7.
go back to reference Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S, Talmor D: Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009, 180: 821-827.PubMedCentralCrossRefPubMed Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S, Talmor D: Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009, 180: 821-827.PubMedCentralCrossRefPubMed
8.
go back to reference Mecott GA, Al-Mousawi AM, Gauglitz GG, Herndon DN, Jeschke MG: The role of hyperglycemia in burned patients: Evidence-based studies. Shock 2010, 33: 5-13. 10.1097/SHK.0b013e3181af0494CrossRefPubMed Mecott GA, Al-Mousawi AM, Gauglitz GG, Herndon DN, Jeschke MG: The role of hyperglycemia in burned patients: Evidence-based studies. Shock 2010, 33: 5-13. 10.1097/SHK.0b013e3181af0494CrossRefPubMed
9.
go back to reference Kendall DM, Cuddihy RM, Bergenstal RM: Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med 2009,122(6 Suppl):S37-50. 10.1016/j.amjmed.2009.03.015CrossRefPubMed Kendall DM, Cuddihy RM, Bergenstal RM: Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med 2009,122(6 Suppl):S37-50. 10.1016/j.amjmed.2009.03.015CrossRefPubMed
10.
go back to reference Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986, 63: 492-498. 10.1210/jcem-63-2-492CrossRefPubMed Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986, 63: 492-498. 10.1210/jcem-63-2-492CrossRefPubMed
11.
go back to reference Meier JJ, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck MA, Holst JJ, Schmidt WE, Gallwitz B: Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med 2004, 32: 848-851. 10.1097/01.CCM.0000114811.60629.B5CrossRefPubMed Meier JJ, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck MA, Holst JJ, Schmidt WE, Gallwitz B: Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med 2004, 32: 848-851. 10.1097/01.CCM.0000114811.60629.B5CrossRefPubMed
12.
go back to reference Deane AM, Chapman MJ, Fraser RJ, Burgstad CM, Besanko LK, Horowitz M: The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study. Crit Care 2009, 13: R67. 10.1186/cc7874PubMedCentralCrossRefPubMed Deane AM, Chapman MJ, Fraser RJ, Burgstad CM, Besanko LK, Horowitz M: The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study. Crit Care 2009, 13: R67. 10.1186/cc7874PubMedCentralCrossRefPubMed
13.
go back to reference Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF: Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 1987, 84: 3434-3438. 10.1073/pnas.84.10.3434PubMedCentralCrossRefPubMed Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF: Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 1987, 84: 3434-3438. 10.1073/pnas.84.10.3434PubMedCentralCrossRefPubMed
14.
go back to reference Pratley RE, Gilbert M: Targeting Incretins in Type 2 Diabetes: Role of GLP-1 receptor agonists and DPP-4 inhibitors. Rev Diabet Stud 2008, 5: 73-94. 10.1900/RDS.2008.5.73PubMedCentralCrossRefPubMed Pratley RE, Gilbert M: Targeting Incretins in Type 2 Diabetes: Role of GLP-1 receptor agonists and DPP-4 inhibitors. Rev Diabet Stud 2008, 5: 73-94. 10.1900/RDS.2008.5.73PubMedCentralCrossRefPubMed
15.
go back to reference Eng J, Kleinman WA, Singh L, Singh G, Raufman JP: Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992, 267: 7402-7405.PubMed Eng J, Kleinman WA, Singh L, Singh G, Raufman JP: Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992, 267: 7402-7405.PubMed
16.
go back to reference Linnebjerg H, Park S, Kothare PA, Trautmann ME, Mace K, Fineman M, Wilding I, Nauck M, Horowitz M: Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes. Regul Pept 2008, 151: 123-129. 10.1016/j.regpep.2008.07.003CrossRefPubMed Linnebjerg H, Park S, Kothare PA, Trautmann ME, Mace K, Fineman M, Wilding I, Nauck M, Horowitz M: Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes. Regul Pept 2008, 151: 123-129. 10.1016/j.regpep.2008.07.003CrossRefPubMed
17.
go back to reference Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, Goke B: Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem 1993, 268: 19650-19655.PubMed Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, Goke B: Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem 1993, 268: 19650-19655.PubMed
18.
go back to reference Pereira C, Murphy K, Jeschke M, Herndon DN: Post burn muscle wasting and the effects of treatments. Int J Biochem Cell Biol 2005, 37: 1948-1961. 10.1016/j.biocel.2005.05.009CrossRefPubMed Pereira C, Murphy K, Jeschke M, Herndon DN: Post burn muscle wasting and the effects of treatments. Int J Biochem Cell Biol 2005, 37: 1948-1961. 10.1016/j.biocel.2005.05.009CrossRefPubMed
19.
go back to reference Mlcak RP, Jeschke MG, Barrow RE, Herndon DN: The influence of age and gender on resting energy expenditure in severely burned children. Ann Surg 2006, 244: 121-130. 10.1097/01.sla.0000217678.78472.d3PubMedCentralCrossRefPubMed Mlcak RP, Jeschke MG, Barrow RE, Herndon DN: The influence of age and gender on resting energy expenditure in severely burned children. Ann Surg 2006, 244: 121-130. 10.1097/01.sla.0000217678.78472.d3PubMedCentralCrossRefPubMed
22.
go back to reference Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF: Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 1970, 19: 644-655.CrossRefPubMed Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF: Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 1970, 19: 644-655.CrossRefPubMed
23.
go back to reference Rodbard D: Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. Diabetes Technol Ther 2009,11(Suppl 1):S55-67.PubMed Rodbard D: Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. Diabetes Technol Ther 2009,11(Suppl 1):S55-67.PubMed
24.
go back to reference Perley MJ, Kipnis DM: Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest 1967, 46: 1954-1962. 10.1172/JCI105685PubMedCentralCrossRefPubMed Perley MJ, Kipnis DM: Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest 1967, 46: 1954-1962. 10.1172/JCI105685PubMedCentralCrossRefPubMed
25.
go back to reference Gromada J, Holst JJ, Rorsman P: Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch 1998, 435: 583-594. 10.1007/s004240050558CrossRefPubMed Gromada J, Holst JJ, Rorsman P: Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch 1998, 435: 583-594. 10.1007/s004240050558CrossRefPubMed
26.
go back to reference Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hufner M, Schmiegel WH: Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002, 87: 1239-1246. 10.1210/jc.87.3.1239CrossRefPubMed Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hufner M, Schmiegel WH: Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002, 87: 1239-1246. 10.1210/jc.87.3.1239CrossRefPubMed
27.
go back to reference Nielsen LL, Young AA, Parkes DG: Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004, 117: 77-88. 10.1016/j.regpep.2003.10.028CrossRefPubMed Nielsen LL, Young AA, Parkes DG: Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004, 117: 77-88. 10.1016/j.regpep.2003.10.028CrossRefPubMed
28.
go back to reference Idris I, Patiag D, Gray S, Donnelly R: Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. Biochem Pharmacol 2002, 63: 993-996. 10.1016/S0006-2952(01)00924-8CrossRefPubMed Idris I, Patiag D, Gray S, Donnelly R: Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. Biochem Pharmacol 2002, 63: 993-996. 10.1016/S0006-2952(01)00924-8CrossRefPubMed
29.
go back to reference Egi M, Bellomo R, Reade MC: Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy? Crit Care 2009, 13: 302. 10.1186/cc7755PubMedCentralCrossRefPubMed Egi M, Bellomo R, Reade MC: Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy? Crit Care 2009, 13: 302. 10.1186/cc7755PubMedCentralCrossRefPubMed
30.
go back to reference Jeha GS, Heptulla RA: Newer therapeutic options for children with diabetes mellitus: theoretical and practical considerations. Pediatr Diabetes 2006, 7: 122-138. 10.1111/j.1399-543X.2006.00159.xCrossRefPubMed Jeha GS, Heptulla RA: Newer therapeutic options for children with diabetes mellitus: theoretical and practical considerations. Pediatr Diabetes 2006, 7: 122-138. 10.1111/j.1399-543X.2006.00159.xCrossRefPubMed
31.
go back to reference Raman VS, Heptulla RA: New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res 2009, 65: 370-374. 10.1203/PDR.0b013e3181975ee4CrossRefPubMed Raman VS, Heptulla RA: New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res 2009, 65: 370-374. 10.1203/PDR.0b013e3181975ee4CrossRefPubMed
32.
go back to reference Srinivasan BT, Jarvis J, Khunti K, Davies MJ: Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad Med J 2008, 84: 524-531. 10.1136/pgmj.2008.067918CrossRefPubMed Srinivasan BT, Jarvis J, Khunti K, Davies MJ: Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad Med J 2008, 84: 524-531. 10.1136/pgmj.2008.067918CrossRefPubMed
33.
go back to reference Greenfield JR, Farooqi IS, Keogh JM, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM: Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 2009, 89: 106-113. 10.3945/ajcn.2008.26362PubMedCentralCrossRefPubMed Greenfield JR, Farooqi IS, Keogh JM, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM: Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 2009, 89: 106-113. 10.3945/ajcn.2008.26362PubMedCentralCrossRefPubMed
Metadata
Title
The use of exenatide in severely burned pediatric patients
Authors
Gabriel A Mecott
David N Herndon
Gabriela A Kulp
Natasha C Brooks
Ahmed M Al-Mousawi
Robert Kraft
Haidy G Rivero
Felicia N Williams
Ludwik K Branski
Marc G Jeschke
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9222

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