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高剂量氨基酸给药可在 2 型糖尿病患者中实现合成代谢反应,与血糖控制无关:一项随机临床试验。

High dose amino acid administration achieves an anabolic response in type 2 diabetic patients that is independent of glycaemic control: A randomized clinical trial.

机构信息

School of Dietetics and Human Nutrition, McGill University, Montreal, Canada.

Department of Anaesthesia, St. Clara Hospital, Basel, Switzerland.

出版信息

Clin Nutr. 2018 Aug;37(4):1163-1171. doi: 10.1016/j.clnu.2017.04.016. Epub 2017 May 3.

DOI:10.1016/j.clnu.2017.04.016
PMID:28527646
Abstract

BACKGROUND & AIMS: Surgical stress provokes protein catabolism and hyperglycaemia that is enhanced in patients with type 2 diabetes (T2DM), and increases perioperative morbidity. This study hypothesized that perioperative administration of high dose intravenous (IV) amino acids (AA) will augment protein balance in T2DM patients receiving tight plasma glucose control via continuous IV insulin compared to standard plasma glucose control via subcutaneous (SC) insulin sliding scale.

METHODS

Eighteen patients with well-controlled T2DM (HbA1C% < 7.1) undergoing colorectal surgery were assigned randomly to receive standard glucose control (6-10 mmol/l, SC insulin, n = 9) or tight glucose control (4-6 mmol/l, IV insulin, n = 9). Both groups received general anaesthesia and epidural analgesia. AA (1 ml/kg h Aminoven™ 10%, ∼2.4 g/kg d) were infused via a peripheral vein for two 3-h periods: at the beginning of surgery and in the post-operative care unit. Whole-body protein and glucose kinetics were assessed by stable isotope tracers, L-[1-C]leucine and [6,6-H]glucose.

RESULTS

Whole-body protein balance was positive after surgery in all patients. Since protein synthesis, breakdown and leucine oxidation were comparable in both groups, whole body protein balance was not different (p = 0.605). Tight glucose control suppressed endogenous glucose production (EGP, p < 0.001) and increased glucose clearance (p < 0.001) compared to standard glucose control during both study periods. No episode of hypoglycaemia occurred in either group.

CONCLUSION

High-dose perioperative AA administration under optimal anti-catabolic care with epidural analgesia was effective in achieving a positive protein balance in T2DM patients undergoing surgery that was independent of glycaemic control strategy. Continuous IV insulin maintained normoglycaemia by inhibiting EGP and increasing glucose clearance. Improved glucose control, without a pronounced increase in protein balance with the intravenous insulin regimen, suggests perioperative protein metabolism may be less sensitive to insulin than is glucose.

摘要

背景与目的

手术应激会引起蛋白质分解代谢和高血糖,这种情况在 2 型糖尿病(T2DM)患者中更为严重,并增加围手术期发病率。本研究假设,与皮下胰岛素推注的标准血糖控制相比,围手术期给予高剂量静脉(IV)氨基酸(AA)治疗将增加接受严格血糖控制的 T2DM 患者的蛋白质平衡,方法:18 例血糖控制良好的 T2DM(HbA1C%<7.1)患者接受结直肠手术,随机分为标准血糖控制组(6-10mmol/L,皮下胰岛素,n=9)或严格血糖控制组(4-6mmol/L,IV 胰岛素,n=9)。两组均接受全身麻醉和硬膜外镇痛。AA(1ml/kg·h AminovenTM10%,约 2.4g/kg·d)通过外周静脉输注 2 个 3 小时周期:手术开始时和术后监护病房。通过稳定同位素示踪剂 L-[1-C]亮氨酸和[6,6-H]葡萄糖评估全身蛋白质和葡萄糖动力学。结果:所有患者术后均出现全身蛋白质正平衡。由于两组的蛋白质合成、分解和亮氨酸氧化相似,全身蛋白质平衡无差异(p=0.605)。与标准血糖控制相比,严格血糖控制在两个研究期间均抑制内源性葡萄糖生成(EGP,p<0.001)并增加葡萄糖清除率(p<0.001)。两组均未发生低血糖事件。结论:在硬膜外镇痛的最佳抗分解代谢治疗下,围手术期给予高剂量 AA 治疗可有效实现 T2DM 患者的正蛋白质平衡,与血糖控制策略无关。持续 IV 胰岛素通过抑制 EGP 和增加葡萄糖清除率维持正常血糖。改善血糖控制,而静脉胰岛素方案对蛋白质平衡的明显增加没有增加,提示围手术期蛋白质代谢对胰岛素的敏感性可能低于葡萄糖。

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