• Xing Zhang, Jie Xu, Xiaoqing Cai, Lele Ji, Jia Li, Bing Cao, Jun Li, Dahai Hu, Yan Li, Haichang Wang, Lize Xiong, Ruiping Xiao, and Feng Gao.
• 1Department of Physiology, School of Basic Medical Sciences, The Fourth Military Medical University, Xi'an, China. 2Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 3Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 4Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 5Institute of Molecular Medicine, Peking University, Beijing, China.
• Crit. Care Med.. 2014 Jun 1;42(6):e472-80.

ObjectiveHyperglycemia often occurs in severe burns; however, the underlying mechanisms and importance of managing postburn hyperglycemia are not well recognized. This study was designed to investigate the dynamic changes of postburn hyperglycemia and the underlying mechanisms and to evaluate whether early glycemic control is beneficial in severe burns.DesignProspective, randomized experimental study.SettingAnimal research laboratory.SubjectsSprague-Dawley rats.InterventionsAnesthetized rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive vehicle, insulin, and a soluble form of receptor for advanced glycation endproducts treatments. An in vitro study was performed on cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment.Measurements And Main ResultsWe found that blood glucose change presented a distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour postburn, respectively. Acute insulin resistance evidenced by impaired insulin signaling and glucose uptake occurred at 3-hour postburn, which was associated with the second hyperglycemia and positively correlated with mortality. Mechanistically, we found that serum carboxymethyllysine, a dominant species of advanced glycation endproducts, increased within 1-hour postburn, preceding the occurrence of insulin resistance. More importantly, treatment of animals with soluble form of receptor for advanced glycation endproducts, blockade of advanced glycation endproducts signaling, alleviated severe burn-induced insulin resistance. In addition, early hyperglycemic control with insulin not only reduced serum carboxymethyllysine but also blunted postburn insulin resistance and reduced mortality.ConclusionsThese findings suggest that severe burn-induced insulin resistance is partly at least mediated by serum advanced glycation endproducts and positively correlated with mortality. Early glycemic control with insulin or inhibition of advanced glycation endproducts with soluble form of receptor for advanced glycation endproducts ameliorates postburn insulin resistance.

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