Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.
Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.
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DOI：
10.1139/apnm-2015-0213
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
McVerry BJ
中科院分区：
文献类型：
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作者：
Singamsetty S;Shah FA;Guo L;Watanabe Y;McDonald S;Sharma R;Zhang Y;Alonso LC;O'Donnell CP;McVerry BJ
脓毒症期间高血糖的发展与发病率和死亡率增加有关。营养支持是重症监护病房的常见做法，但其代谢作用尚不清楚。本研究的目的是在临床相关的脓毒症小鼠模型中确定早期低热量提供对高血糖发展的影响。C57BL/6J小鼠行股动脉和股静脉插管，然后进行盲肠结扎穿刺（CLP）或假手术和低剂量静脉葡萄糖或生理盐水输注。24小时后测量血糖、血浆胰岛素和细胞因子。另外的脓毒症小鼠接受高胰岛素-正血糖钳夹或静脉注射胰岛素与葡萄糖同时注射，以测定全身胰岛素敏感性并测试胰岛素逆转高血糖的功效。葡萄糖输注和单独CLP均未引起高血糖。在脓毒症小鼠中早期开始低水平葡萄糖会产生不同的血糖反应：49%的小鼠维持正常血糖（血糖<200），27%的小鼠出现严重高血糖（血糖≥600）。与对照组小鼠或维持正常血糖的CLP小鼠相比，高血糖与炎症增加、胰岛素分泌和敏感性降低有关。胰岛素防止进展到严重的高血糖，但在重建血糖控制，一旦高血糖已经发展无效。总之，在脓毒症小鼠中，早期开始临床相关的低水平葡萄糖（约每日热量需求的20%）会导致高血糖，类似于急性糖尿病表型，其特征是胰岛素敏感性降低、胰岛素分泌减少和炎症反应增加。
Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose <200) and 27% developed severe hyperglycemia (blood glucose≥600). Hyperglycemia was associated with increased inflammation and reduced insulin secretion and sensitivity compared with control mice or CLP mice maintaining euglycemia. Insulin prevented the progression to severe hyperglycemia but was ineffective in reestablishing glycemic control once hyperglycemia had developed. In conclusion, early initiation of clinically relevant low-level dextrose (~20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.