Department of Surgery, University of Florida, Gainesville, FL.
University of Arkansas for Medical Sciences, Little Rock, AR.
J Am Coll Surg. 2019 Jul;229(1):58-67.e1. doi: 10.1016/j.jamcollsurg.2019.04.014. Epub 2019 Apr 13.
Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin secretion, cellular glucose uptake, and has immune-regulatory functions. Glucagon-like peptide-1 is markedly altered after trauma and sepsis, but the implications remain unclear.
We performed an analysis of a prospective, longitudinal cohort study of critically ill surgical patients with sepsis. Patient characteristics and clinical data were collected, as well as peripheral blood sampling for biomarker analysis, out to 28 days after sepsis onset. We prospectively adjudicated sepsis diagnosis, severity, clinical outcomes, and 6-month follow-up.
The cohort included 157 septic surgical patients with significant physiologic derangement (Maximum Sequential Organ Failure Assessment [SOFA] score 8, interquartile range [IQR] 4 to 11), a high rate of multiple organ failure (50.3%), and septic shock (24.2%). Despite high disease severity, both early death (<14 days; n = 4, 2.9%) and overall inpatient mortality were low (n = 12, 7.6%). However, post-discharge 6-month mortality was nearly 3-fold higher (19.7%). Both GLP-1 and interleukin [IL]-6 levels were significantly elevated for 21 days (p ≤ 0.01) in patients who developed chronic critical illness (CCI) compared with patients with a rapid recovery. Elevated GLP-1 at 24 hours was a significant independent predictor for the development of CCI after controlling for IL-6 and glucose levels (p = 0.027), and at day 14 for death or severe functional disability at 6 months (WHO/Zubrod score 4-5, p = 0.014).
Elevated GLP-1 within 24 hours of sepsis is a predictor of early death or persistent organ dysfunction. Among early survivors, persistently elevated GLP-1 levels at day 14 are strongly predictive of death or severe functional disability at 6 months. Persistently elevated GLP-1 levels may be a marker of a nonresolving catabolic state that is associated with muscle wasting and dismal outcomes after sepsis and chronic critical illness.
胰高血糖素样肽-1（GLP-1）是一种源自肠道的肠促胰岛素激素，可刺激胰岛素分泌、细胞葡萄糖摄取，并具有免疫调节功能。创伤和脓毒症后 GLP-1 明显改变，但意义仍不清楚。
我们对脓毒症的危重症外科患者进行了一项前瞻性、纵向队列研究的分析。收集了患者特征和临床数据，以及发病后 28 天内的外周血样本进行生物标志物分析。我们前瞻性地判定了脓毒症的诊断、严重程度、临床结局和 6 个月的随访。
该队列包括 157 例患有严重生理紊乱的脓毒症外科患者（最大序贯器官衰竭评估[SOFA]评分 8 分，四分位间距 [IQR] 4 至 11 分）、高器官衰竭发生率（50.3%）和脓毒性休克（24.2%）。尽管疾病严重程度高，但早期死亡（<14 天；n=4，2.9%）和总住院死亡率均较低（n=12，7.6%）。然而，出院后 6 个月的死亡率几乎高了 3 倍（19.7%）。与快速恢复的患者相比，发生慢性危重病（CCI）的患者的 GLP-1 和白细胞介素[IL]-6 水平在 21 天内均显著升高（p≤0.01）。在控制 IL-6 和葡萄糖水平后，24 小时时升高的 GLP-1 是发生 CCI 的独立显著预测因素（p=0.027），而在第 14 天，是 6 个月时死亡或严重功能障碍（WHO/Zubrod 评分 4-5，p=0.014）的独立预测因素。
脓毒症后 24 小时内升高的 GLP-1 是早期死亡或持续器官功能障碍的预测指标。在早期幸存者中，第 14 天持续升高的 GLP-1 水平强烈预测 6 个月时死亡或严重功能障碍。持续升高的 GLP-1 水平可能是一种非解决性分解代谢状态的标志物，与脓毒症和慢性危重病后的肌肉消耗和不良结局相关。
