Dynamic characteristics of blood glucose time series during the course of critical illness: Effects of intensive insulin therapy and relative association with mortality

Geert Meyfroidt, Daniel M. Keenan, Xin Wang, Pieter J. Wouters, Johannes D Veldhuis, Greet Van Den Berghe

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Objectives: To assess the effect of intensive insulin therapy on blood glucose amplitude variation and pattern irregularity in critically ill patients. To assess the association of these blood glucose signal characteristics with hospital mortality, independent of blood glucose level. Design: Retrospective analysis of the databases of two previously published randomized controlled trials. Setting: University hospital, 56-bed adult surgical intensive care unit and 17-bed medical intensive care unit. PATIENTS: One thousand five-hundred forty-eight surgical intensive care unit patients, admitted between February 2000 and January 2001, and 1200 medical intensive care unit patients, admitted between March 2002 and May 2005. Interventions: In the two randomized controlled trials, patients were randomized to receive either intensive insulin therapy (targeting normoglycemia, between 4.4 and 6.1mmol/L) or conventional insulin therapy (infusing insulin when blood glucose levels were >12 mmol/L and stopping at 10 mmol/L). Measurements and Main Results: Intensive insulin therapy significantly lowered mean blood glucose (5.8 vs. 8.4 mmol/L), hyperglycemic index (0.8 vs. 3.2 mmol/L), and glycemic penalty index (26 vs. 53), but it increased the mean daily difference between minimum and maximum blood glucose (mean daily δ blood glucose; 4.0 vs. 3.3 mmol/L). There was no significant effect on the standard deviation of the blood glucose measurements or on jack-knifed approximate entropy. In multivariable logistic regression analysis, corrected for baseline risk factors, blood glucose levels outside the normoglycemic range, higher mean daily δ blood glucose, higher standard deviation blood glucose, and higher jack-knifed approximate entropy were independently associated with hospital mortality. Conclusions: The Leuven intensive insulin therapy strategy increased mean daily δ blood glucose while not affecting standard deviation blood glucose and jack-knifed approximate entropy. Increased blood glucose amplitude variation and pattern irregularity were associated with mortality, irrespective of blood glucose level. The reduced mortality observed with intensive insulin therapy in the Leuven trials cannot be attributed to an effect on blood glucose amplitude variation or entropy. Reducing amplitude variation and entropy of the blood glucose signal, irrespective of blood glucose concentration, may produce clinical benefits.

Original languageEnglish (US)
Pages (from-to)1021-1029
Number of pages9
JournalCritical Care Medicine
Volume38
Issue number4
DOIs
StatePublished - Apr 2010

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Critical Illness
Blood Glucose
Insulin
Mortality
Entropy
Therapeutics
Intensive Care Units
Critical Care
Hospital Mortality
Randomized Controlled Trials
Glycemic Index

Keywords

  • Blood glucose
  • Hospital mortality
  • Hyperglycemia
  • Insulin
  • Intensive care
  • Logistic models

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Dynamic characteristics of blood glucose time series during the course of critical illness : Effects of intensive insulin therapy and relative association with mortality. / Meyfroidt, Geert; Keenan, Daniel M.; Wang, Xin; Wouters, Pieter J.; Veldhuis, Johannes D; Van Den Berghe, Greet.

In: Critical Care Medicine, Vol. 38, No. 4, 04.2010, p. 1021-1029.

Research output: Contribution to journalArticle

Meyfroidt, Geert ; Keenan, Daniel M. ; Wang, Xin ; Wouters, Pieter J. ; Veldhuis, Johannes D ; Van Den Berghe, Greet. / Dynamic characteristics of blood glucose time series during the course of critical illness : Effects of intensive insulin therapy and relative association with mortality. In: Critical Care Medicine. 2010 ; Vol. 38, No. 4. pp. 1021-1029.
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AU - Wouters, Pieter J.

AU - Veldhuis, Johannes D

AU - Van Den Berghe, Greet

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N2 - Objectives: To assess the effect of intensive insulin therapy on blood glucose amplitude variation and pattern irregularity in critically ill patients. To assess the association of these blood glucose signal characteristics with hospital mortality, independent of blood glucose level. Design: Retrospective analysis of the databases of two previously published randomized controlled trials. Setting: University hospital, 56-bed adult surgical intensive care unit and 17-bed medical intensive care unit. PATIENTS: One thousand five-hundred forty-eight surgical intensive care unit patients, admitted between February 2000 and January 2001, and 1200 medical intensive care unit patients, admitted between March 2002 and May 2005. Interventions: In the two randomized controlled trials, patients were randomized to receive either intensive insulin therapy (targeting normoglycemia, between 4.4 and 6.1mmol/L) or conventional insulin therapy (infusing insulin when blood glucose levels were >12 mmol/L and stopping at 10 mmol/L). Measurements and Main Results: Intensive insulin therapy significantly lowered mean blood glucose (5.8 vs. 8.4 mmol/L), hyperglycemic index (0.8 vs. 3.2 mmol/L), and glycemic penalty index (26 vs. 53), but it increased the mean daily difference between minimum and maximum blood glucose (mean daily δ blood glucose; 4.0 vs. 3.3 mmol/L). There was no significant effect on the standard deviation of the blood glucose measurements or on jack-knifed approximate entropy. In multivariable logistic regression analysis, corrected for baseline risk factors, blood glucose levels outside the normoglycemic range, higher mean daily δ blood glucose, higher standard deviation blood glucose, and higher jack-knifed approximate entropy were independently associated with hospital mortality. Conclusions: The Leuven intensive insulin therapy strategy increased mean daily δ blood glucose while not affecting standard deviation blood glucose and jack-knifed approximate entropy. Increased blood glucose amplitude variation and pattern irregularity were associated with mortality, irrespective of blood glucose level. The reduced mortality observed with intensive insulin therapy in the Leuven trials cannot be attributed to an effect on blood glucose amplitude variation or entropy. Reducing amplitude variation and entropy of the blood glucose signal, irrespective of blood glucose concentration, may produce clinical benefits.

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