Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate.

Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Research Abstract Details 

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Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Abstract Text:

Melanie G Cree,Jennifer J Zwetsloot,David N Herndon,Ting Qian,Beatrice Morio,Ricki Fram,Arthur P Sanford,Asle Aarsland,Robert R Wolfe,

OBJECTIVE: To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to determine the efficacy of PPAR-alpha agonism for alleviating insulin resistance in this population. SUMMARY BACKGROUND DATA: Hyperglycemia following trauma, especially burns, is well documented. However, the underlying insulin resistance is not well understood, and there are limited treatment options. METHODS: Twenty-one children 4 to 16 years of age with >40% total body surface area burns were enrolled in a double-blind, prospective, placebo-controlled randomized trial. Whole body and liver insulin sensitivity were assessed with a hyperinsulinemic-euglycemic clamp, and insulin signaling and mitochondrial function were measured in muscle biopsies taken before and after approximately 2 weeks of either placebo (PLA) or 5 mg/kg of PPAR-alpha agonist fenofibrate (FEN) treatment, within 3 weeks of injury. RESULTS: The change in average daily glucose concentrations was significant between groups after treatment (146 +/- 9 vs. 161 +/- 9 mg/dL PLA and 158 +/- 7 vs. 145 +/- 4 FEN; pretreatment vs. posttreatment; P = 0.004). Insulin-stimulated glucose uptake increased significantly in FEN (4.3 +/- 0.6 vs. 4.5 +/- 0.7 PLA and 5.2 +/- 0.5 vs. 7.6 +/- 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003). Insulin trended to suppress hepatic glucose release following fenofibrate treatment (P = 0.06). Maximal mitochondrial ATP production from pyruvate increased significantly after fenofibrate (P = 0.001) and was accompanied by maintained levels of cytochrome C oxidase and citrate synthase activity levels. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 in response to insulin increased significantly following fenofibrate treatment (P = 0.04 for both). CONCLUSIONS: Fenofibrate treatment started within 1 week postburn and continued for 2 weeks significantly decreased plasma glucose concentrations by improving insulin sensitivity, insulin signaling, and mitochondrial glucose oxidation. Fenofibrate may be a potential new therapeutic option for treating insulin resistance following severe burn injury.

Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Publishing Authors By Initials

MG Cree,JJ Zwetsloot,DN Herndon,T Qian,B Morio,R Fram,AP Sanford,A Aarsland,RR Wolfe,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Annals of surgery

VOLUME: 245

Page Numbers: 214-21

Journal Abbreviation: Ann. Surg.

ISSN: 0003-4932

DAY: 3

MONTH: Feb

YEAR: 2007

Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372354

Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Keywords Mesh Terms:

KEYWORDS: Treatment Outcome

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Information

Substance Name: Procetofen

Registry Number: 49562-28-9

Grant and Affiliation Information for Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate.

AFFILIATION: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555, USA. mecree@utmb.edu

Country: United States

AGENCY: United States NIGMS

GRANT: R01-GM56687

ACRONYM: GM

MEDLINETA: Ann Surg

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER: NCT00361751

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