Intensive insulin treatment in critically ill trauma patients normalizes glucose by reducing endogenous glucose production

• Critical illness is associated with insulin resistance and hyperglycemia. Intensive insulin treatment to normalize blood glucose during feeding has been shown to improve morbidity and mortality in patients in intensive care. The mechanisms behind the glucose-controlling effects of insulin in stress are not well understood. Six previously healthy, severely traumatized patients (injury severity score > 15) were studied early (24-48 h) after trauma. Endogenous glucose production (EGP) and whole-body glucose disposal (WGD) were measured (6,6-(2)H(2)-glucose) at basal, during total parenteral nutrition (TPN), and during TPN plus insulin to normalize blood glucose (TPN+I). Six matched volunteers served as controls. At basal and TPN, concentrations of glucose and insulin were higher in patients (P < 0.05). During TPN+I, insulin concentrations were 30-fold higher in patients. At basal, WGD and EGP were 30% higher in patients (P < 0.05). During TPN, EGP decreased in both groups but less in patients, resulting in 110% higher EGP than controls (P < 0.05). Normoglycemia coincided with reduced EGP, resulting in similar rates in both groups. WGD did not change during TPN or TPN+I and was not different between the groups. In conclusion, in healthy subjects, euglycemia is maintained during TPN at physiological insulin concentrations by a reduction of EGP, whereas WGD is maintained at basal levels. In traumatized patients, hyperglycemia is due to increased EGP. In contrast to controls, normalization of glucose concentration during TPN needs high insulin infusion rates and is accounted for by a reduction in EGP, whereas WGD is not increased.

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