SIMULATED POSTAGGRESSION METABOLISM IN HEALTHY-SUBJECTS - METABOLIC CHANGES AND INSULIN-RESISTANCE

Postaggression metabolism (PAM) is difficult to study in critically il l patients. The objective of this study was to simulate PAM in healthy subjects to quantify insulin sensitivity under these conditions. Six healthy men (age, 24 +/- 1 years; body mass index, 22.0 +/- 0.7 kg/m(2 ) [mean +/- SE]) received an intravenous (IV) infusion of insulin-coun teracting hormones (epinephrine 100 ng/kg/min, glucagon 16 ng/kg/min, hydrocortisone 5 mu g/kg/min, and growth hormone [GH]-releasing hormon e 50 mu g/h) for 4 hours in addition to glucose (270 mg/kg/h). Control experiments used glucose only. In additional experiments, insulin sen sitivity was measured by a two-step hyperinsulinemic glucose clamp wit h and without concomitant hormone infusion (insulin infusion rate, 2.5 and 5.0 mU/kg/min for hormone infusion or 1.0 and 2.5 mU/kg/min for c ontrol experiments). Plasma stress hormones reached levels comparable to severe PAM (epinephrine, 1,085 +/- 89 pg/mL; glucagon, 1,100 +/- 11 4 pg/mL; cortisone, 1,004 +/- 32 ng/mL; and GH, 20.6 +/- 6.1 pg/mL) in the hormone infusion experiment. This resulted in hyperglycemia and h yperinsulinemia (steady-state blood glucose, 19.7 +/- 0.4 mmol/L; seru m insulin, 352 +/- 8 pmol/L) in comparison to the control experiments with glucose infusion only (maximal blood glucose 7.2 +/- 0.8 mmol/L; serum insulin, 110 +/- 16 pmol/L). The insulin sensitivity index (S-I) was 88% +/- 6% lower during hormone infusion (0.6 +/- 0.4 mL/min/m(2) /mu U/min) compared with the control experiments (4.5 +/- 1.3 mL/min/m (2)/mu U/min). Infusion of insulin-counteracting hormones at high dose s allows simulation of the changes in carbohydrate metabolism observed in PAM in healthy subjects. The observed profound decrease in insulin sensitivity explains the hyperglycemia observed in nondiabetic critic ally ill patients. With this experimental setup, standardized investig ations of therapeutic interventions in PAM should be possible.