Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children

Objective: To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Design: Prospective, randomized study. Setting: An acute pediatric burn unit in a tertiary teaching hospital. Patients: Children, 4-18 yrs old, with total body surface area burned ≥40% and who arrived within 1 wk after injury were enrolled in the study. Interventions: Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose ≤215 mg/dL. Measurements and main results: Twenty patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 ± 124 to 1925 ± 291 kcal/m•day; p =.02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 ± 0.8 conventional insulin therapy vs. 6.8 ± 0.9 mg/kg•min intensive insulin therapy; p =.5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 ± 1.3 intensive insulin therapy versus 4.8 ± 0.6 mg/kg•min conventional insulin therapy, p =.005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 ± 0.9 vs. 2.5 ± 0.6 mg/kg•min; intensive insulin therapy vs. conventional insulin therapy; p =.03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 ± 0.1 to 1.7 ± 0.1 μm O2/CS/mg protein/min for state 3, p =.004; and 0.7 ± 0.1 to 1.3 ± 0.1 μm O2/CS/mg protein/min for state 4, p <.002), whereas conventional insulin therapy remained at the same level of activity (0.9 ± 0.1 to 0.8 ± 0.1.μm O2/CS/mg protein/min for state 3, p =.4; 0.6 ± 0.03 to 0.7 ± 0.1 μm O2/CS/mg protein/min, p =.6). Conclusion: Controlling blood glucose levels ≤120 mg/dL using an intensive insulin therapy protocol improves insulin sensitivity and mitochondrial oxidative capacity while decreasing resting energy expenditure in severely burned children.