治疗高血糖可改善癌症患者大手术后的骨骼肌蛋白质代谢。

Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery.

作者信息

Biolo Gianni, De Cicco Marcello, Lorenzon Stefania, Dal Mas Viviana, Fantin Dario, Paroni Rita, Barazzoni Rocco, Zanetti Michela, Iapichino Gaetano, Guarnieri Gianfranco

机构信息

Division of Internal Medicine, Department of Clinical, Morphological and Technological Sciences, University of Trieste, Trieste, Italy.

出版信息

Crit Care Med. 2008 Jun;36(6):1768-75. doi: 10.1097/CCM.0b013e318174de32.

DOI:10.1097/CCM.0b013e318174de32

PMID:18496366

Abstract

OBJECTIVE

Cancer and surgical stress interact to aggravate insulin resistance, protein catabolism, and glutamine depletion in skeletal muscle. We compared the effects of insulin-mediated euglycemia and moderate hyperglycemia on kinetics of protein and selected amino acids in skeletal muscle of female cancer patients after major surgery.

DESIGN

In each patient, a 24-hr period of insulin-mediated tight euglycemia (mean blood glucose, 5.8 +/- 0.4 mmol/L) preceded or followed a 24-hr control period of moderate hyperglycemia (mean blood glucose, 9.6 +/- 0.6 mmol/L) on the first and second day after surgery, in randomized order, according to a crossover experimental design.

SETTING

Intensive care unit, cancer hospital.

PATIENTS

Cancer patients after abdominal radical surgery combined with intraoperative radiation therapy.

INTERVENTIONS

Intensive (57 +/- 11 units/24 hrs) and conventional (25 +/- 5 units/24 hrs) insulin treatment during total parenteral nutrition.

MEASUREMENTS AND MAIN RESULTS

Muscle metabolism was assessed at the end of each 24-hr period of euglycemia and of hyperglycemia by leg arteriovenous catheterization with stable isotopic tracers. We found that euglycemia as compared with hyperglycemia was associated with higher (p < .05) fractional glucose uptake (16% +/- 4% vs. 9% +/- 3%); higher (p < .05) muscle protein synthesis and neutral net protein balance (-3 +/- 3 vs. -11 +/- 3 nmol phenylalanine x 100 mL(-1) x min(-1), respectively); lower (-52% +/- 12%, p < .01) muscle nonprotein leucine disposal (an index of leucine oxidation) and higher (p < .05) plasma leucine concentrations; and higher (3.6 +/- 1.7 times, p < .01) net de novo muscle glutamine synthesis and plasma glutamine concentrations (p < .05). Euglycemia was associated with higher (23% +/- 7%, p < .05) plasma concentrations of arginine but did not affect either arginine release from muscle or plasma concentration and muscle flux of asymmetrical dimethylarginine. Rate of muscle proteolysis correlated (p < .05) with muscle release of asymmetrical dimethylarginine.

CONCLUSIONS

Treating hyperglycemia improves skeletal muscle protein and amino acid metabolism in cancer patients after major surgery.

摘要

目的

癌症与手术应激相互作用，会加重骨骼肌中的胰岛素抵抗、蛋白质分解代谢及谷氨酰胺消耗。我们比较了胰岛素介导的血糖正常和中度高血糖对接受大手术后女性癌症患者骨骼肌中蛋白质及特定氨基酸动力学的影响。

设计

根据交叉实验设计，对每位患者在术后第一天和第二天，随机安排先进行24小时胰岛素介导的严格血糖正常期（平均血糖，5.8±0.4 mmol/L），随后进行24小时中度高血糖对照期（平均血糖，9.6±0.6 mmol/L），或先进行24小时中度高血糖对照期，随后进行24小时胰岛素介导的严格血糖正常期。

地点

癌症医院重症监护病房。

患者

接受腹部根治性手术并术中放疗后的癌症患者。

干预措施

全胃肠外营养期间采用强化胰岛素治疗（57±11单位/24小时）和常规胰岛素治疗（25±5单位/24小时）。

测量指标及主要结果

在血糖正常期和高血糖期的每24小时结束时，通过腿部动静脉插管并使用稳定同位素示踪剂评估肌肉代谢。我们发现，与高血糖相比，血糖正常时的葡萄糖摄取分数更高（p < 0.05）（分别为16%±4%对9%±3%）；肌肉蛋白质合成和中性净蛋白质平衡更高（p < 0.05）（分别为 -3±3对 -11±3 nmol苯丙氨酸×100 mL⁻¹×min⁻¹）；肌肉非蛋白质亮氨酸处置（亮氨酸氧化指标）更低（-52%±12%，p < 0.01），血浆亮氨酸浓度更高（p < 0.05）；肌肉谷氨酰胺净从头合成和血浆谷氨酰胺浓度更高（3.6±1.7倍，p < 0.01）（p < 0.05）。血糖正常与血浆精氨酸浓度更高（23%±7%，p < 0.05）相关，但不影响肌肉中精氨酸的释放或不对称二甲基精氨酸的血浆浓度及肌肉通量。肌肉蛋白水解速率与肌肉中不对称二甲基精氨酸的释放相关（p < 0.05）。