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;42(6):e472-80. doi: 10.1097/CCM.0000000000000314.
Hyperglycemia 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.
Prospective, randomized experimental study.
Animal research laboratory.
Sprague-Dawley rats.
Anesthetized 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.
We 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.
These 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.
严重烧伤常伴有高血糖；然而，其发生机制和管理高血糖的重要性尚未得到充分认识。本研究旨在探讨烧伤后高血糖的动态变化及其发生机制，并评估早期血糖控制对严重烧伤是否有益。
前瞻性、随机实验研究。
动物实验研究室。
Sprague-Dawley 大鼠。
麻醉大鼠接受 40%总体表面积的全层皮肤烧伤，并随机接受载体、胰岛素和可溶性晚期糖基化终产物受体治疗。体外研究采用羧甲基赖氨酸处理的 H9C2 细胞。
我们发现血糖变化呈明显模式，烧伤后 0.5 和 3 小时分别出现两次高血糖。3 小时后出现急性胰岛素抵抗，表现为胰岛素信号和葡萄糖摄取受损，与第二次高血糖有关，并与死亡率呈正相关。从机制上讲，我们发现血清羧甲基赖氨酸（晚期糖基化终产物的主要产物）在烧伤后 1 小时内增加，早于胰岛素抵抗的发生。更重要的是，用可溶性晚期糖基化终产物受体治疗动物，阻断晚期糖基化终产物信号，可缓解严重烧伤引起的胰岛素抵抗。此外，早期用胰岛素控制高血糖不仅降低了血清羧甲基赖氨酸，还减轻了烧伤后胰岛素抵抗，降低了死亡率。
这些发现表明，严重烧伤引起的胰岛素抵抗至少部分是由血清晚期糖基化终产物介导的，与死亡率呈正相关。早期用胰岛素或可溶性晚期糖基化终产物受体控制高血糖可改善烧伤后胰岛素抵抗。
