Skip to main content

Advertisement

SpringerLink
Log in

Close relationship between strict blood glucose control, including suppression of blood glucose variability, and mortality reduction in acutely ill patients with glucose intolerance investigated by means of a bedside-type artificial pancreas

  • Original Article
  • Published:
Journal of Artificial Organs Aims and scope Submit manuscript

Abstract

The purpose of this study was to elucidate the relationship between strict control of blood glucose (BG) and mortality reduction with the use of an artificial pancreas (AP). Patients were evaluated in the (1) early phase (E phase: mean 3.3 ± 2.6 days after admission, n = 84) and in the (2) late phase (L phase: mean 9.9 ± 3.3 days, n = 88), and were classified into a (1) group with a higher daily mean BG level (BGm) (BGmXa: BGm above Xmg/dl) and a (2) group with a lower BGm (BGmXb: BGm below Xmg/dl). Each group was classified into a (1) subgroup with a higher daily standard deviation of the BG levels (BGsd) and a (2) subgroup with a lower BGsd. In the E phase, the (1) mortality of the BGm200a group was significantly higher than that of the BGm200b group (56 vs. 29%, p < 0.05), and (2) in the BGm200b group, the mortality of the subgroup with a BGsd above 14 mg/dl was significantly higher than that with a BGsd below 14 mg/dl (46 vs. 17%, p < 0.025). In the L phase, the mortality of the BGm175a group was significantly higher than that of the BGm175b group (50 vs. 28%, p < 0.05). In conclusion, (1) a higher BGm and (2) higher BGsd in the E phase were prognostic risk factors. Based on the findings, it was considered that the target for BG control should be set at (1) BGm below 200 mg/dl and BGsd below 14 mg/dl in the E phase, and (2) BGm below 175 mg/dl in the L phase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. The Diabetic Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med. 1993;329:977–86.

    Article  Google Scholar 

  2. United kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylurea or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS33). Lancet. 1998;352:837–53.

    Article  Google Scholar 

  3. Malmberg K. Prospective randomized study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus: DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. B M J. 1997;314:1512–5.

    CAS  Google Scholar 

  4. 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;67:352–62.

    Article  CAS  PubMed  Google Scholar 

  5. Van den Berghe G, Wouters P, Weekers F, Werwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Buillon R. Intensive insulin therapy in the critically ill patients. N Eng J Med. 2001;345:1359–67.

    Article  Google Scholar 

  6. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Buillon R. Intensive insulin therapy in the Medical ICU. N Engl J Med. 2006;354:449–61.

    Article  PubMed  Google Scholar 

  7. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. JAMA. 2003;290:2041–7.

    Article  CAS  PubMed  Google Scholar 

  8. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79:992–1000.

    Article  PubMed  Google Scholar 

  9. The International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296–327.

    Article  Google Scholar 

  10. Taylor JH, Beilman GJ. Hyperglycemia in the intensive care unit: no longer just a marker of illness severity. Surg Infect. 2005;6:233–45.

    Article  Google Scholar 

  11. Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, Colman PG, Chambers BR, Davis SM. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003;34:2208–14.

    Article  CAS  PubMed  Google Scholar 

  12. Vogelzang M, van der Horst ICC, Nijsten MWN. Hyperglycaemic index as a tool to assess glucose control: a retrospective study. Crit Care. 2004;8:R122–7.

    Article  PubMed  Google Scholar 

  13. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, Nadkarni V. Association of timing, duration and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med. 2004;5:329–36.

    Article  PubMed  Google Scholar 

  14. Krinsley JS, Jones RL. Cost analysis of intensive glycemic control in critically ill adult patients. Chest. 2006;129:644–50.

    Article  PubMed  Google Scholar 

  15. Van den Berhge G, Wouters PJ, Kesteloot K, Hilleman DE. Analysis of healthcare resource utilization with intensive Insulin therapy in critically ill patients. Crit Care Med. 2006;34:612–6.

    Google Scholar 

  16. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complicat. 2005;19:178–81.

    Article  PubMed  Google Scholar 

  17. Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S, Wilson DM. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics. 2006;118:173–9.

    Article  PubMed  Google Scholar 

  18. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006;105:244–52.

    Article  CAS  PubMed  Google Scholar 

  19. Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, Van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C, Muller J, Van Cromphaut S, Van den Berghe G. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomized controlled study. Lancet. 2009;373:547–56.

    Article  CAS  PubMed  Google Scholar 

  20. Brunkhorst FM, Engel C, Bloos F, Hellmann AM, 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. for the German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.

    Article  CAS  PubMed  Google Scholar 

  21. NICE-SUGAR Study Investigators, Finster 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 Eng J Med. 2009;360:1283–97.

    Article  Google Scholar 

  22. Laver S, Preston S, Turner D, Mckinstry C, Padkin A. Implementing intensive insulin therapy: development and audit of the bath insulin protocol. Anaesth Intensive Care. 2004;32:311–6.

    CAS  PubMed  Google Scholar 

  23. Kanji S, Singh A, Tierney M, Meggison H, McIntyre L, Hebert PC. Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults. Intensive Care Med. 2004;30:804–10.

    Article  PubMed  Google Scholar 

  24. Van den Berhge G, Wilmer A, Milants I, Wouters PJ, Bouckaert B, Bruyninckx F, Bouillon R, Schetz M. Intensive insulin therapy in mixed medical/surgical intensive care units. Benefit versus harm. Diabetes. 2006;55:3151–9.

    Article  Google Scholar 

  25. Orford NR. Intensive insulin therapy in septic shock. Crit Care Resusc. 2006;8:230–4.

    PubMed  Google Scholar 

  26. McNay EC, Williamson A, McCrimmon RJ, Sherwin RS. Cognitive and neural hippocampal effects of long-term moderate recurrent hypoglycemia. Diabetes. 2006;55:1088–95.

    Article  CAS  PubMed  Google Scholar 

  27. Mackenzie I, Ingle S, Zaidi S, Buczaski S. Tight glycemic control: a survey of intensive care practice in large English hospitals. Intensive Care Med. 2005;31:1136.

    Article  PubMed  Google Scholar 

  28. Plank J, Blaha J, Cordingley J, Wilinska ME, Chassin LJ, Morgan C, Squire S, Haluzik M, Kremen J, Svacina S, Toller W, Plasnik A, Ellmerer M, Hovorka R, Pieber TR. Multicentric, randomized, controlled trial to evaluate blood glucose control by the model predictive control algorithm versus routine glucose management protocols in intensive care unit patients. Diabetes Care. 2006;29:271–6.

    Article  PubMed  Google Scholar 

  29. De Block C, Keenoy BMY, Van Gaal L, Rogiers P. Intensive insulin therapy in the intensive care unit. Diabetes Care. 2006;29:1750–6.

    Article  PubMed  Google Scholar 

  30. Scalea TM, Bochicchio BV, Bochicchio KM, Johnson SB, Joshi M, Pyle A. Tight glycemic control in critically injured trauma patients. Ann Surg. 2007;246:605–12.

    Article  PubMed  Google Scholar 

  31. Collier B, Dossett LA, May AK, Diaz JJ. Glucose control and the inflammatory response. Nutr Clin Pract. 2008;23:3–15.

    Article  PubMed  Google Scholar 

  32. Vriesendorp TM, van Santen S, DeVries H, De Jonge E, Rosendaal FR, Schultz MJ, Hoekstra JBL. Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med. 2006;34:96–101.

    Article  PubMed  Google Scholar 

  33. Hoshino M, Haraguchi Y, Kirita M. Nutritional treatment of septic patients with decreased glucose tolerance with the artificial pancreas. In 7th World Congress of the International Society for Artificial Organs [Abstract]. No. G-02-36989 1989; p 308.

  34. Haraguchi Y, Hoshino M, Kirita M. Intravenous hyperalimentation and artificial endocrine pancreas for patients with impaired glucose tolerance. In 25th Congress of European Society for Surgical Research [Abstract]. No. 178 1990; p 84.

  35. Hoshino M, Haraguchi Y, Hirasawa H, Sakai M, Saegusa H, Hayashi K, Horita N, Ohsawa H. Close relationship of tissue plasminogen activator-plasminogen activator inhibitor-1 complex with multiple organ dysfunction syndrome investigated by means of the artificial pancreas. Crit Care. 2001;5:88–9.

    Article  CAS  PubMed  Google Scholar 

  36. Hoshino M, Haraguchi Y, Hirasawa H, Mizushima I, Tanaka C, Morita Y, Yokoi T, Sakai M. Measurement of insulin clearance and factors affecting insulin clearance in septic patients with glucose intolerance—analysis under strict blood glucose control by means of bedside-type artificial pancreas. Chiba Med J. 2006;82:149–61.

    CAS  Google Scholar 

  37. Hoshino M, Haraguchi Y, Mizushima I, Kajiwara S, Takagi M. Significance of the suppression of blood glucose variability in acutely ill severe patients with glucose intolerance evaluated by means of bedside-type artificial pancreas [Abstract] Crit Care. 2008;12 Suppl 2:S60.

  38. Hoshino M, Haraguchi Y, Mizushima I, Sakai M, Kajiwara S, Takagi M. High blood glucose variability in acute phase is one of the most important risk factors relating to the outcome in acutely ill severe patients with glucose intolerance. [Abstract] Crit Care. 2009;13 Suppl 1:S49–50.

    Google Scholar 

  39. Hoshino M, Haraguchi Y, Muzushima I, Sakai M. Recent progress in mechanical artificial pancreas. J Artif Organs. 2009;12:141–9.

    Article  CAS  PubMed  Google Scholar 

  40. Bone RC, Balk RA, Cerra FB, 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;101:1644–55.

    Article  CAS  PubMed  Google Scholar 

  41. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units. Crit Care Med. 1998;26:1793–800.

    CAS  PubMed  Google Scholar 

  42. 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 Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–73.

    Article  PubMed  Google Scholar 

  43. Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma. 2004;56:1058–62.

    Article  PubMed  Google Scholar 

  44. Bochicchio GV, Sung Jin, Joshi M, Bochicchio K, Johnson SB, Meyer W, Scalea TM. Persistent hyperglycemia is predictive of outcome in critically ill trauma patients. J Trauma. 2005;58:921–4.

  45. Dossett LA, Cao H, Mowery NT, Dortch MJ, Morris JM Jr, May AK. Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surg. 2008;74:679–85.

    PubMed  Google Scholar 

  46. Ali NA, O’Brien JM Jr, Dungan K, Phillips G, Marsh CB, Lemeshow S, Connors AF Jr, Preiser JC. Glucose variability and mortality in patients with sepsis. Crit Care Med. 2008;36:2316–21.

    Article  PubMed  Google Scholar 

  47. Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36:3008–13.

    Article  CAS  PubMed  Google Scholar 

  48. Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281:E924–30.

    CAS  PubMed  Google Scholar 

  49. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells. Diabetes. 2003;52:2795–804.

    Article  CAS  PubMed  Google Scholar 

  50. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7.

    Article  CAS  PubMed  Google Scholar 

  51. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Guigliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106:2067–72.

    Article  CAS  PubMed  Google Scholar 

  52. Holtfreter B, Bandt C, Kuhn SO, Grunwald U, Lehmann C, Schutt C, Grundling M. Serum osmolality and outcome in intensive care unit patients. Acuta Anaesthesiol Scand. 2006;50:970–7.

    Article  CAS  Google Scholar 

  53. Otto N, Schindler R, Lun A, Boenisch O, Frei U, Oppert M. Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro. Crit Care. 2008;12:R107.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Shisei Hospital, 1221 Shimookutomi, Sayama, Saitama, 350-1332, Japan

    Masami Hoshino

  2. Department of Surgery, National Hospital Organization Disaster Medical Center, Tokyo, Japan

    Yoshikura Haraguchi

  3. Department of Clinical Engineering, Nippon Engineering College, Tokyo, Japan

    Iwanori Mizushima

  4. Department of Clinical Engineering, Tokyo Women’s Medical University Hospital, Tokyo, Japan

    Motohiro Sakai

Authors
  1. Masami Hoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshikura Haraguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iwanori Mizushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Motohiro Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masami Hoshino.

Appendix

Appendix

See Table 2.

Table 2 “MOF score” calculated using the criteria proposed by the Japanese Association for Critical Care Medicine (1990)
Full size table

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoshino, M., Haraguchi, Y., Mizushima, I. et al. Close relationship between strict blood glucose control, including suppression of blood glucose variability, and mortality reduction in acutely ill patients with glucose intolerance investigated by means of a bedside-type artificial pancreas. J Artif Organs 13, 151–160 (2010). https://doi.org/10.1007/s10047-010-0509-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10047-010-0509-9

Keywords

Search

Navigation