Intensive Versus Conventional Insulin Therapy in Nondiabetic Patients Receiving Parenteral Nutrition After D2 Gastrectomy for Gastric Cancer: A Randomized Controlled Trial

  • Shougen Cao
  • Yanbing Zhou
  • Dong Chen
  • Zhaojian Niu
  • Dongsheng Wang
  • Liang Lv
  • Yu Li
Original Article

Abstract

Background

This study was used to compare the effects of intensive insulin therapy with conventional insulin therapy on postoperative outcomes among nondiabetic patients receiving parenteral nutrition following D2 gastrectomy for gastric cancer.

Method

A total of 248 eligible patients were randomly assigned to receive intensive insulin therapy targeting a blood glucose level between 4.4 and 6.1 mmol/l [intensive group (n = 125)] or conventional insulin therapy targeting a blood glucose level less than 11.0 mmol/l [conventional group (n = 123)] during the postoperative period.

Results

Mean blood glucose concentrations were lower in the intensive group than in the conventional group. Severe hypoglycemia defined as blood glucose ≤2.2 mmol/l occurred in eight (6.4%) patients in the intensive group vs one (0.8%) patient in the conventional group (P = 0.036). One (0.8%) patient died in the intensive group vs two (1.6%) patients in the conventional group (P = 0.620). However, intensive insulin therapy significantly reduced overall postoperative complications rate (from 25.2% to 13.6%, P = 0.024). Moreover, both insulin resistance indicated as HOMA-IR and HLA-DR expression on monocytes were improved in the intensive group.

Conclusions

Intensive insulin therapy significantly reduced the postoperative short-term morbidity but not mortality among nondiabetic patients receiving parenteral nutrition after D2 gastrectomy. The benefits may be due to the suppression of insulin resistance and improvement of HLA-DR expression on monocytes.

Keywords

Intensive insulin therapy Gastric cancer Parenteral nutrition Insulin resistance HLA-DR Postoperative complications 

Notes

Grant Support

This study was supported by the Health Science and Technology Development Project of Shandong (2005HZ024).

Conflict of interest

There is no potential and real conflict to any third party.

References

  1. 1.
    Cuschieri A, Weeden S, Fielding J, Bancewicz J, Craven J, Joypaul V, Sydes M, Fayers P. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer 1999;79:1522–1530.PubMedCrossRefGoogle Scholar
  2. 2.
    Hartgrink HH, van de Velde CJ, Putter H, Bonenkamp JJ, Klein Kranenbarg E, Songun I, Welvaart K, van Krieken JH, Meijer S, Plukker JT, van Elk PJ, Obertop H, Gouma DJ, van Lanschot JJ, Taat CW, de Graaf PW, von Meyenfeldt MF, Tilanus H, Sasako M. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 2004;22:2069–2077.PubMedCrossRefGoogle Scholar
  3. 3.
    McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2009;33:277–316.PubMedCrossRefGoogle Scholar
  4. 4.
    Ziegler TR. Parenteral nutrition in the critically ill patient. N Engl J Med 2009;361:1088–1097.PubMedCrossRefGoogle Scholar
  5. 5.
    van den 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Ascione R, Rogers CA, Rajakaruna C, Angelini GD. Inadequate blood glucose control is associated with in-hospital mortality and morbidity in diabetic and nondiabetic patients undergoing cardiac surgery. Circulation 2008;118:113–123.PubMedCrossRefGoogle Scholar
  7. 7.
    Pasquel FJ, Spiegelman R, McCauley M, Smiley D, Umpierrez D, Johnson R, Rhee M, Gatcliffe C, Lin E, Umpierrez E, Peng L, Umpierrez GE. Hyperglycemia during total parenteral nutrition: an important marker of poor outcome and mortality in hospitalized patients. Diabetes Care 2010;33:739–741.PubMedCrossRefGoogle Scholar
  8. 8.
    Sarkisian S, Fenton TR, Shaheen AA, Raman M. Parenteral nutrition-associated hyperglycemia in noncritically ill inpatients is associated with higher mortality. Can J Gastroenterol 2010;24:453–457.PubMedGoogle Scholar
  9. 9.
    Kumar PR, Crotty P, Raman M. Hyperglycemia in hospitalized patients receiving parental nutrition is associated with increased morbidity and mortality: a review. Gastroenterol Res Pract 2011Google Scholar
  10. 10.
    Van den 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.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Kajitani T. The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification. Jpn J Surg 1981;11:127–139.PubMedCrossRefGoogle Scholar
  13. 13.
    Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352–360.PubMedCrossRefGoogle Scholar
  14. 14.
    Cao SG, Ren JA, Shen B, Chen D, Zhou YB, Li JS. Intensive versus conventional insulin therapy in type 2 diabetes patients undergoing D2 gastrectomy for gastric cancer: a randomized controlled trial. World J Surg 2011;35:85–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Am J Infect Control 1992;20:271–274.PubMedCrossRefGoogle Scholar
  16. 16.
    Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 1992;101:1481–1483.PubMedCrossRefGoogle Scholar
  17. 17.
    Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57–63.PubMedCrossRefGoogle Scholar
  18. 18.
    Mohn A, Marcovecchio M, Chiarelli F. Validity of HOMA-IR as index of insulin resistance in obesity. J Pediatr 2006;148:565–566.PubMedGoogle Scholar
  19. 19.
    Cheung NW, Napier B, Zaccaria C, Fletcher JP. Hyperglycemia is associated with adverse outcomes in patients receiving total parenteral nutrition. Diabetes Care 2005;28:2367–2371.PubMedCrossRefGoogle Scholar
  20. 20.
    Lin LY, Lin HC, Lee PC, Ma WY, Lin HD. Hyperglycemia correlates with outcomes in patients receiving total parenteral nutrition. Am J Med Sci 2007;333:261–265.PubMedCrossRefGoogle Scholar
  21. 21.
    Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005;64:1348–1353.PubMedCrossRefGoogle Scholar
  22. 22.
    Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004;79:992–1000.PubMedCrossRefGoogle Scholar
  23. 23.
    Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 2008;300:933–944.PubMedCrossRefGoogle Scholar
  24. 24.
    Aragon D. Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control. Am J Crit Care 2006;15:370–377.PubMedGoogle Scholar
  25. 25.
    Van den Berghe G, Wouters PJ, Kesteloot K, Hilleman DE. Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients. Crit Care Med 2006;34:612–616.PubMedGoogle Scholar
  26. 26.
    Krinsley JS, Jones RL. Cost analysis of intensive glycemic control in critically ill adult patients. Chest 2006;129:644–650.PubMedCrossRefGoogle Scholar
  27. 27.
    Ljungqvist O. Insulin resistance and outcomes in surgery. J Clin Endocrinol Metab 2010;95:4217–4219.PubMedCrossRefGoogle Scholar
  28. 28.
    Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care 1999;2:69–78.PubMedCrossRefGoogle Scholar
  29. 29.
    Sato H, Carvalho G, Sato T, Lattermann R, Matsukawa T, Schricker T. The association of preoperative glycemic control, intraoperative insulin sensitivity, and outcomes after cardiac surgery. J Clin Endocrinol Metab 2010;95:4338–4344.PubMedCrossRefGoogle Scholar
  30. 30.
    Leibovici L, Yehezkelli Y, Porter A, Regev A, Krauze I, Harell D. Influence of diabetes mellitus and glycaemic control on the characteristics and outcome of common infections. Diabet Med 1996;13:457–463.PubMedCrossRefGoogle Scholar
  31. 31.
    Clement S, Braithwaite SS, Magee MF, Ahmann A, Smith EP, Schafer RG, Hirsch IB. Management of diabetes and hyperglycemia in hospitals. Diabetes Care 2004;27:553–591.PubMedCrossRefGoogle Scholar
  32. 32.
    Ceriello A, Quagliaro L, D'Amico M, Di Filippo C, Marfella R, Nappo F, Berrino L, Rossi F, Giugliano D. Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 2002;51:1076–1082.PubMedCrossRefGoogle Scholar
  33. 33.
    Polk HC, Jr., Fink MP, Laverdiere M, Wilson SE, Garber GE, Barie PS, Hebert JC, Cheadle WG. Prospective randomized study of piperacillin/tazobactam therapy of surgically treated intra-abdominal infection. The Piperacillin/Tazobactam Intra-Abdominal Infection Study Group. Am Surg 1993;59:598–605.PubMedGoogle Scholar
  34. 34.
    Ditschkowski M, Kreuzfelder E, Rebmann V, Ferencik S, Majetschak M, Schmid EN, Obertacke U, Hirche H, Schade UF, Grosse-Wilde H. HLA-DR expression and soluble HLA-DR levels in septic patients after trauma. Ann Surg 1999;229:246–254.PubMedCrossRefGoogle Scholar
  35. 35.
    Kawasaki T, Ogata M, Kawasaki C, Tomihisa T, Okamoto K, Shigematsu A. Surgical stress induces endotoxin hyporesponsiveness and an early decrease of monocyte mCD14 and HLA-DR expression during surgery. Anesth Analg 2001;92:1322–1326.PubMedCrossRefGoogle Scholar
  36. 36.
    Venet F, Tissot S, Debard AL, Faudot C, Crampe C, Pachot A, Ayala A, Monneret G. Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock. Crit Care Med 2007;35:1910–1917.PubMedCrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2011

Authors and Affiliations

  • Shougen Cao
    • 1
  • Yanbing Zhou
    • 1
  • Dong Chen
    • 1
  • Zhaojian Niu
    • 1
  • Dongsheng Wang
    • 1
  • Liang Lv
    • 1
  • Yu Li
    • 1
  1. 1.Department of General SurgeryAffiliated Hospital of Medical College Qingdao UniversityQingdaoChina

Personalised recommendations