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

Ricki Y. Fram, Melanie G. Cree, Robert R. Wolfe, Ronald P. Mlcak, Ting Qian, David L. Chinkes, David Herndon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1475-1483
Number of pages9
JournalCritical Care Medicine
Volume38
Issue number6
DOIs
StatePublished - Jun 2010

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Insulin Resistance
Insulin
Therapeutics
Energy Metabolism
Blood Glucose
Burn Units
Proteins
Pediatrics
Glucose
Glucose Clamp Technique
Palmitates
Body Surface Area
Liver
Tertiary Care Centers
Teaching Hospitals

Keywords

  • Burns
  • Child
  • Critical care
  • Hyperglycemia
  • Hyperinsulinism
  • Insulin
  • Pediatrics

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Fram, R. Y., Cree, M. G., Wolfe, R. R., Mlcak, R. P., Qian, T., Chinkes, D. L., & Herndon, D. (2010). Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children. Critical Care Medicine, 38(6), 1475-1483. https://doi.org/10.1097/CCM.0b013e3181de8b9e

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children. / Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Mlcak, Ronald P.; Qian, Ting; Chinkes, David L.; Herndon, David.

In: Critical Care Medicine, Vol. 38, No. 6, 06.2010, p. 1475-1483.

Research output: Contribution to journalArticle

Fram, RY, Cree, MG, Wolfe, RR, Mlcak, RP, Qian, T, Chinkes, DL & Herndon, D 2010, 'Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children', Critical Care Medicine, vol. 38, no. 6, pp. 1475-1483. https://doi.org/10.1097/CCM.0b013e3181de8b9e
Fram, Ricki Y. ; Cree, Melanie G. ; Wolfe, Robert R. ; Mlcak, Ronald P. ; Qian, Ting ; Chinkes, David L. ; Herndon, David. / Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children. In: Critical Care Medicine. 2010 ; Vol. 38, No. 6. pp. 1475-1483.
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abstract = "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.",
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AU - Fram, Ricki Y.

AU - Cree, Melanie G.

AU - Wolfe, Robert R.

AU - Mlcak, Ronald P.

AU - Qian, Ting

AU - Chinkes, David L.

AU - Herndon, David

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N2 - 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.

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KW - Critical care

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