Metabolic, Endocrine, and Immune Effects of Stress Hyperglycemia in a Rabbit Model of Prolonged Critical Illness

Endocrinology. 2003 Dec;144(12):5329-38. doi: 10.1210/en.2003-0697. Epub 2003 Aug 28.


Stress hyperglycemia is frequent in critically ill patients. The aim of this study was to investigate the effect of blood glucose control with insulin on endocrine, metabolic, and immune function in an animal model of severe injury. Seventy-two hours after alloxan injection and exogenous insulin infusion combined with continuous iv parenteral nutrition, male New Zealand White rabbits received a burn injury and were allocated to a normoglycemic (n = 17) or hyperglycemic (n = 13) group. In the normoglycemic group, blood glucose levels were kept between 3.3 and 6.1 mmol/liter by insulin infusion, whereas in the hyperglycemic group blood glucose levels were maintained at 13.8-16.6 mmol/liter. Blood was drawn for biochemical analysis at regular time points. At 24 and 72 h after burn injury, immune function of monocytes was assessed in vitro. Maintenance of normoglycemia with exogenous insulin after severe trauma to a large extent prevented weight loss, lactic acidosis, and hyponatremia. Furthermore, within 3 d after injury, the intervention improved phagocytosis of monocytes investigated in fresh cells by more than a mean 150% (P = 0.006) and after 24-h incubation with or without lipopolysaccharide by more than a mean 4-fold (P = 0.001) and 2-fold (P = 0.05), respectively. Oxidative killing after 24-h incubation was also improved by 2-fold (P = 0.05), but no effect on chemotaxis was detected. Concomitantly, inflammation and stress-induced growth hormone hypersecretion were suppressed. Prevention of catabolism, acidosis, excessive inflammation, and impaired innate immune function may explain previously documented beneficial effects of intensive insulin therapy on outcome of critical illness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloxan
  • Animals
  • Blood Gas Analysis
  • Blood Glucose
  • Body Weight / drug effects
  • Body Weight / physiology
  • Burns / immunology
  • Burns / metabolism
  • Critical Illness*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / metabolism
  • Disease Models, Animal
  • Endocrine System / immunology
  • Endocrine System / metabolism
  • Growth Hormone / blood
  • Hyperglycemia / drug therapy
  • Hyperglycemia / immunology*
  • Hyperglycemia / metabolism*
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Lactic Acid / blood
  • Lipids / blood
  • Macrophages / immunology
  • Male
  • Parenteral Nutrition
  • Rabbits
  • Stress, Physiological / immunology*
  • Stress, Physiological / metabolism*


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Lactic Acid
  • Alloxan
  • Growth Hormone