Mesotten Dieter, Swinnen Johannes V, Vanderhoydonc Frank, Wouters Pieter J, Van den Berghe Greet
Department of Intensive Care Medicine, University Hospital Gasthuisberg, Catholic University Leuven, B-3000 Leuven, Belgium.
J Clin Endocrinol Metab. 2004 Jan;89(1):219-26. doi: 10.1210/jc.2003-030760.
Compared with the conventional approach, which recommended only insulin therapy when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood glucose levels less than 6.1 mmol/liter with intensive insulin therapy has shown to reduce intensive care mortality, acute renal failure, critical illness polyneuropathy, and bloodstream infections in critically ill patients by about 40%. This study of 363 patients, requiring intensive care for more than 7 d and randomly assigned to either conventional or intensive insulin therapy, examines the effects of intensive insulin therapy on glucose and lipid homeostasis and their respective impact on the improved outcome. Intensive insulin therapy effectively normalized blood glucose levels within 24 h, both in survivors and nonsurvivors. Intensive insulin therapy also increased serum levels of low-density lipoprotein (P = 0.007) and high-density lipoprotein (P = 0.005), whereas it suppressed the elevated serum triglyceride concentrations (P < 0.0001). Multivariate logistic regression analysis, corrected for baseline univariate risk factors and the effect on inflammation, indicated that lipid rather than glucose control independently determined the beneficial effects of intensive insulin therapy on morbidity and mortality. In postmortem biopsies obtained from 74 patients who died in the intensive care unit, intensive insulin therapy increased mRNA levels of skeletal muscle glucose transporter 4 (P = 0.02) and hexokinase (P = 0.03), unlike those of hepatic glucokinase. In conclusion, our data suggest that intensive insulin therapy normalizes blood glucose levels through stimulation of peripheral glucose uptake and concomitantly partially restores the abnormalities in the serum lipid profile, which may have contributed significantly to the improved outcome of protracted critical illness.
与传统方法相比，传统方法仅在血糖水平超过12毫摩尔/升时推荐胰岛素治疗，而强化胰岛素治疗将血糖水平严格维持在6.1毫摩尔/升以下已显示可使重症患者的重症监护死亡率、急性肾衰竭、重症疾病多发性神经病和血流感染降低约40%。这项对363例需要重症监护超过7天且随机分配接受传统或强化胰岛素治疗的患者的研究，考察了强化胰岛素治疗对葡萄糖和脂质稳态的影响及其对改善预后的各自影响。强化胰岛素治疗在24小时内有效使幸存者和非幸存者的血糖水平正常化。强化胰岛素治疗还提高了血清低密度脂蛋白水平（P = 0.007）和高密度脂蛋白水平（P = 0.005），而抑制了血清甘油三酯浓度的升高（P < 0.0001）。经基线单变量风险因素和对炎症的影响校正的多变量逻辑回归分析表明，脂质而非血糖控制独立决定了强化胰岛素治疗对发病率和死亡率的有益影响。在从74例在重症监护病房死亡的患者身上获取的尸检活检中，强化胰岛素治疗增加了骨骼肌葡萄糖转运蛋白4（P = 0.02）和己糖激酶（P = 0.03）的mRNA水平，与肝葡萄糖激酶不同。总之，我们的数据表明，强化胰岛素治疗通过刺激外周葡萄糖摄取使血糖水平正常化，并同时部分恢复血清脂质谱异常，这可能对延长的危重病的改善预后有显著贡献。
