Langouche L, Mesotten D, Vanhorebeek I
Division and Laboratory of Intensive Care Medicine, Department of Acute Medical Sciences, Faculty of Medicine, Katholieke Universiteit Leuven, O&N1 Herestraat 49 bus 503 - B-3000 Leuven.
Verh K Acad Geneeskd Belg. 2010;72(3-4):149-63.
Critically ill patients face a high risk of death, which is mostly due to non-resolving multiple organ failure. The plethora of endocrine and metabolic disturbances that hallmark critical illness may play a key role. The major part of our research performed during the period 2004-2009 focused on the disturbed glucose metabolism that commonly develops during critical illness. The onset of this research interest was the landmark randomized clinical study on strict blood glucose control (80-110 mg/ dl) with intensive insulin therapy performed by Prof. Van den Berghe and our clinical team members. This study, published in 2001 in the New England Journal of Medicine, showed reduced morbidity and improved survival with intensive insulin therapy versus toleration of hyperglycemia up to 215 mg/dl. This review summarizes our findings in both patients and animal models on mechanisms contributing to the clinical benefits of strict blood glucose control. Intensive insulin therapy appeared to lower blood glucose levels by ameliorating insulin sensitivity and stimulation of glucose uptake in skeletal muscle, whereas hepatic insulin resistance was not affected. The therapy also improved the lipid profile and the immune response and attenuated inflammation. Maintenance of strict normoglycemia appeared essentially most important, rather than elevating insulin levels. Avoiding hyperglycemia protected the endothelium and the mitochondria. In our animal model, nutritional interventions counteracted the hypercatabolic state of critical illness and insulin improved myocardial contractility, but only when normoglycemia was maintained. Interestingly, we identified the adipose tissue as a functional storage depot for toxic metabolites during critical illness.
危重症患者面临着很高的死亡风险，这主要是由于多器官功能衰竭无法缓解所致。危重症所特有的大量内分泌和代谢紊乱可能起关键作用。我们在2004年至2009年期间进行的大部分研究都集中在危重症期间常见的糖代谢紊乱上。这一研究兴趣的起源是范登伯格教授和我们的临床团队成员进行的一项具有里程碑意义的关于强化胰岛素治疗严格控制血糖（80 - 110毫克/分升）的随机临床研究。这项于2001年发表在《新英格兰医学杂志》上的研究表明，与耐受高达215毫克/分升的高血糖相比，强化胰岛素治疗可降低发病率并提高生存率。这篇综述总结了我们在患者和动物模型中关于严格控制血糖带来临床益处的机制的研究结果。强化胰岛素治疗似乎通过改善胰岛素敏感性和刺激骨骼肌摄取葡萄糖来降低血糖水平，而肝胰岛素抵抗未受影响。该治疗还改善了血脂状况和免疫反应，并减轻了炎症。维持严格的正常血糖水平似乎最为重要，而不是提高胰岛素水平。避免高血糖可保护内皮细胞和线粒体。在我们的动物模型中，营养干预可抵消危重症的高分解代谢状态，并且胰岛素可改善心肌收缩力，但前提是维持正常血糖水平。有趣的是，我们发现脂肪组织是危重症期间有毒代谢产物的功能性储存库。
