Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance.
Level 3 - non-randomized controlled study
Controlled non-randomized human experimental crossover study
PubMed 9781632 · doi:10.1016/s0026-0495(98)90334-1
What was done
Six healthy men (mean age 24 ± 1 years, BMI 22.0 ± 0.7 kg/m²) received a 4-hour intravenous infusion of counter-regulatory hormones (epinephrine 100 ng/kg/min, glucagon 16 ng/kg/min, hydrocortisone 5 µg/kg/min, and growth hormone-releasing hormone 50 µg/h) combined with glucose (270 mg/kg/h). Control experiments administered glucose alone. In additional experiments, insulin sensitivity was assessed using a two-step hyperinsulinemic glucose clamp with and without concurrent hormone infusion.
What was found
Hormone infusion generated plasma stress hormone concentrations typical of severe postaggression metabolism (epinephrine 1,085 ± 89 pg/mL, glucagon 1,100 ± 114 pg/mL, cortisone 1,004 ± 32 ng/mL, growth hormone 20.6 ± 6.1 pg/mL). This produced marked hyperglycemia (steady-state blood glucose 19.7 ± 0.4 mmol/L vs. control 7.2 ± 0.8 mmol/L) and hyperinsulinemia (serum insulin 352 ± 8 pmol/L vs. control 110 ± 16 pmol/L). The insulin sensitivity index was 88% ± 6% lower during hormone infusion (0.6 ± 0.4 vs. 4.5 ± 1.3 mL/min/m2/microU/min).
Why it matters
This study shows that elevating stress hormones to concentrations seen in critical illness directly induces severe, acute insulin resistance and hyperglycemia in healthy individuals, providing a controlled human model for testing interventions.
Limits
The sample size was very small (n=6) and restricted entirely to young, healthy men. The abstract does not state whether the order of conditions was randomized. A 4-hour hormone infusion does not capture other aspects of critical illness, such as systemic cytokine release or prolonged metabolic stress.
Cited by
- supports Elevated stress hormones such as cortisol and epinephrine cause acute insulin resistance in humans within hours.