van der Crabben Saskia N, Blümer Regje M E, Stegenga Michiel E, Ackermans Mariëtte T, Endert Erik, Tanck Michael W T, Serlie Mireille J, van der Poll Tom, Sauerwein Hans P
Department of Endocrinology and Metabolism, Academic Medial Center, Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 2009 Feb;94(2):463-8. doi: 10.1210/jc.2008-0761. Epub 2008 Nov 4.
Sepsis-induced hypoglycemia is a well known, but rare, event of unknown origin.
The aim of the study was to obtain insight into the mechanism of sepsis-induced hypoglycemia, focusing on glucose kinetics and insulin sensitivity measured with stable isotopes by using the model of human endotoxemia.
Glucose metabolism was measured during two hyperinsulinemic [insulin levels of 100 pmol/liter (low-dose clamp) and 400 pmol/liter (medium-dose clamp)] euglycemic (5 mmol/liter) clamps on two occasions: without or with lipopolysaccharide (LPS).
The study was conducted at the Academic Medical Center, Metabolic and Clinical Research Unit (Amsterdam, The Netherlands).
Eighteen healthy male volunteers participated in the study.
A hyperinsulinemic euglycemic (5 mmol/liter) clamp with LPS (two groups of six subjects; insulin infusion at rates of either 10 or 40 mU.m(-2).min(-1)) or without LPS (n = 6; both insulin infusions in same subjects).
We measured hepatic and peripheral insulin sensitivity.
Hepatic insulin sensitivity, defined as a decrease in endogenous glucose production during hyperinsulinemia (100 pmol/liter), was higher in the LPS group compared to the control group (P = 0.010). Insulin-stimulated peripheral glucose uptake was higher in both clamps after LPS compared to the control setting (P = 0.006 and 0.010), despite a significant increase in the plasma concentrations of norepinephrine and cytokines in the LPS group during both clamps.
These data indicate that shortly (2 h) after administration of LPS, peripheral and hepatic insulin sensitivity increase. This may contribute to the hypoglycemia occurring in some patients with critical illness, especially in the setting of intensive insulin therapy.
脓毒症诱导的低血糖是一种已知但罕见且病因不明的事件。
本研究旨在深入了解脓毒症诱导低血糖的机制，重点关注通过人体内毒素血症模型利用稳定同位素测量的葡萄糖动力学和胰岛素敏感性。
在两次高胰岛素正常血糖（5毫摩尔/升）钳夹期间测量葡萄糖代谢，两次钳夹的胰岛素水平分别为100皮摩尔/升（低剂量钳夹）和400皮摩尔/升（中剂量钳夹），钳夹分两种情况进行：无脂多糖（LPS）或有脂多糖。
研究在学术医疗中心代谢与临床研究室（荷兰阿姆斯特丹）进行。
18名健康男性志愿者参与了本研究。
进行高胰岛素正常血糖（5毫摩尔/升）钳夹，一组有LPS（两组，每组6名受试者；胰岛素输注速率分别为10或40毫单位·米-2·分钟-1），另一组无LPS（n = 6；同一受试者进行两种胰岛素输注）。
我们测量了肝脏和外周胰岛素敏感性。
与对照组相比，LPS组肝脏胰岛素敏感性更高，肝脏胰岛素敏感性定义为高胰岛素血症（100皮摩尔/升）期间内源性葡萄糖生成减少（P = 0.010）。与对照情况相比，LPS后两次钳夹期间胰岛素刺激的外周葡萄糖摄取均更高（P = 0.006和0.010），尽管LPS组在两次钳夹期间去甲肾上腺素和细胞因子的血浆浓度显著升高。
这些数据表明，给予LPS后不久（2小时），外周和肝脏胰岛素敏感性增加。这可能是一些危重病患者发生低血糖的原因，尤其是在强化胰岛素治疗的情况下。
