title: Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.
abstract: OBJECTIVE
  To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  An acute pediatric burn unit in a tertiary teaching hospital.
  
  
  METHODS
  Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study.
  
  
  METHODS
  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 < or =215 mg/dL.
  
  
  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(2) x 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 x 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 x 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 x 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 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/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 microm O(2)/CS/mg protein/min for state 3, p = .4; 0.6 +/- 0.03 to 0.7 +/- 0.1 microm O(2)/CS/mg protein/min, p = .6).
  
  
  CONCLUSIONS
  Controlling blood glucose levels < or =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.
authors.affiliation: Metabolism Unit and Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA. rfram@uams.edu
authors.forename: Ricki Y
authors.initials: RY
authors.lastname: Fram
authors.forename: Melanie G
authors.initials: MG
authors.lastname: Cree
authors.forename: Robert R
authors.initials: RR
authors.lastname: Wolfe
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mlcak
authors.forename: Ting
authors.initials: T
authors.lastname: Qian
authors.forename: David L
authors.initials: DL
authors.lastname: Chinkes
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002056:Burns / Q000097:blood / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D015331:Cohort Studies; D003422:Critical Care; D004334:Drug Administration Schedule; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010101:Oxygen Consumption
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin
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