Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Crit Care. 2010;14(5):R179. doi: 10.1186/cc9285. Epub 2010 Oct 8.
Hyperglycemia and insulin resistance are well-known features of critical illness and impact the mortality rate, especially in sepsis. Retinol binding protein 4 (RBP4) promotes insulin resistance in mice and is systemically elevated in patients with obesity and type 2 diabetes. We investigated the potential role of RBP4 in critically ill patients.
We conducted a prospective single-center study of serum RBP4 concentrations in critically ill patients. One hundred twenty-three patients (85 with sepsis, 38 without sepsis) were studied at admission to a medical intensive care unit (ICU) before initiation of specific intensive care treatment measures and compared to 42 healthy nondiabetic controls. Clinical data, various laboratory parameters and metabolic and endocrine functions were assessed. Patients were followed for approximately 3 years.
Serum RBP4 was significantly reduced in ICU patients, independently of sepsis, as compared to healthy controls (P < 0.001). Patients with liver cirrhosis as the primary underlying diagnosis for ICU admission had significantly lower RBP4 levels as compared with other ICU patients. Accordingly, in all ICU patients, serum RBP4 closely correlated with liver function and increased with renal failure. No significant differences of serum RBP4 concentrations in septic patients with pulmonary or other origins of sepsis or nonseptic patients could be revealed. Acute phase proteins were inversely correlated with RBP4 in sepsis patients. RBP4 did not differ between patients with or without obesity or preexisting diabetes. However, serum RBP4 levels correlated with endogenous insulin secretion (C-peptide) and insulin resistance (HOMA index). Low serum RBP4 upon admission was an adverse predictor of short-term survival in the ICU, but was not associated with overall survival during long-term follow-up.
Serum RBP4 concentrations are significantly reduced in critically ill patients. The strong associations with hepatic and renal function, insulin resistance and acute mortality collectively suggest a role of RBP4 in the pathogenesis of critical illness, possibly as a negative acute phase reactant, and allow a proposition as a potential novel biomarker for ICU patients.
高血糖和胰岛素抵抗是危重病的显著特征，会影响死亡率，尤其是在脓毒症中。视黄醇结合蛋白 4（RBP4）在小鼠中促进胰岛素抵抗，并且在肥胖和 2 型糖尿病患者中系统性升高。我们研究了 RBP4 在危重病患者中的潜在作用。
我们进行了一项关于危重病患者血清 RBP4 浓度的前瞻性单中心研究。在开始特定的重症监护治疗措施之前，将 123 名患者（85 名脓毒症患者，38 名非脓毒症患者）纳入重症监护病房（ICU），并与 42 名健康非糖尿病对照者进行比较。评估了临床数据、各种实验室参数以及代谢和内分泌功能。患者随访约 3 年。
与健康对照组相比，ICU 患者的血清 RBP4 显著降低，无论是否患有脓毒症（P < 0.001）。因肝硬化而入住 ICU 的患者的 RBP4 水平明显低于其他 ICU 患者。相应地，在所有 ICU 患者中，血清 RBP4 与肝功能密切相关，并随肾功能衰竭而增加。在患有肺部或其他来源的脓毒症或非脓毒症的脓毒症患者中，血清 RBP4 浓度没有显著差异。脓毒症患者的急性期蛋白与 RBP4 呈负相关。在肥胖或患有糖尿病的患者中，血清 RBP4 水平没有差异。然而，血清 RBP4 水平与内源性胰岛素分泌（C 肽）和胰岛素抵抗（HOMA 指数）相关。入院时低血清 RBP4 是 ICU 短期生存率的不良预测指标，但与长期随访期间的总生存率无关。
血清 RBP4 浓度在危重病患者中显著降低。与肝功能和肾功能、胰岛素抵抗和急性死亡率的强相关性表明 RBP4 在危重病发病机制中起作用，可能作为负急性期反应物，并作为 ICU 患者的潜在新型生物标志物。
