血糖变异性与脓毒症患者院内死亡的相关性：系统评价与Meta分析-现代医学

血糖变异性与脓毒症患者院内死亡的相关性：系统评价与Meta分析

作者：毛瑞晓¹ 2 冯贞贞¹ 2 刘文瑞¹ 2 雷斯媛¹ 2 张莹莹³ 郭小川¹ 2 李建生¹ 2

单位：1. 河南中医药大学第一附属医院国家医学中心肺病诊疗中心, 河南郑州 450046;
2. 河南中医药大学呼吸疾病中医药防治省部共建协同创新中心/河南省中医药防治呼吸病重点实验室, 河南郑州 450046;
3. 辽宁中医药大学第二临床学院, 辽宁沈阳 110847

关键词：脓毒症血糖变异性血糖波动血糖变异系数 Meta分析

分类号：R259;R631;R446.1

出版年·卷·期（页码）：2026·54·第六期（903-916）

摘要：

目的：系统评价血糖变异性与脓毒症患者院内死亡的关系，并基于糖尿病状态与胰岛素使用情况分层探讨血糖变异性的亚组差异。方法：检索中国知网、万方、维普、中国生物医学文献服务系统、PubMed、Web of Science和Embase数据库，搜集血糖变异性[血糖变异系数(GLU CV)、血糖标准差(GLU SD)、最大血糖波动幅度(LAGE)、平均血糖波动幅度(MAGE)、血糖差值(GLU dif)和血糖不稳定指数(GLI)等]与脓毒症患者院内死亡相关性的研究，检索时间自建库至2025年7月9日。由2名评价员独立完成文献筛选与数据提取，采用纽卡斯尔-渥太华量表对纳入研究进行文献质量评估，并计算Kappa系数评估2名评价者提取数据的一致性。采用观察性流行病学研究报告指南(STROBE)声明清单对纳入研究进行报告评价。应用RevMan 5.4软件进行Meta分析。结果：纳入25篇研究，共计3 876例患者。按生存结局分组纳入21项队列研究；按血糖变异程度分组纳入4项队列研究。Meta分析结果显示：院内死亡组的GLU CV(SMD=1.065，95%CI 0.563～1.568，P<0.001)、GLU SD(MD=0.812，95%CI 0.443～1.181，P<0.001)、GLU dif(MD=1.152，95%CI 0.688～1.616，P<0.001)、LAGE(MD=2.725，95%CI 1.162～4.288，P<0.001)、MAGE(MD=0.287，95%CI 0.176～0.397，P<0.001)、GLI(SMD=1.938，95%CI 0.467～3.410，P=0.010)均高于存活组，血糖高变异性组的患者院内死亡率高于低变异性组(OR=14.550，95%CI 1.078～196.436，P=0.043)。按糖尿病状态及胰岛素使用情况进行亚组分析显示，合并糖尿病、使用胰岛素控制的院内死亡组GLU CV和GLU SD均高于存活组，差异有统计学意义(均P<0.05)。无糖尿病或未使用胰岛素的患者中，2组间上述指标差异无统计学意义(均P＞0.05)。结论：血糖变异性作为一种经济、简便的指标，其升高可能与脓毒症患者院内死亡风险增加相关，尤其对于合并糖尿病及需胰岛素治疗的患者，血糖变异性升高与不良预后关联更为显著。监测血糖变异性有助于早期风险分层和个体化干预决策。

Objective: To systematically evaluate the association between glycemic variability and in-hospital mortality in patients with sepsis, and to explore subgroup differences stratified by diabetes status and insulin use. Methods: The databases of CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, and Embase were searched for studies on the association between glycemic variability [including glycemic coefficient of variation(GLU CV), standard deviation of blood glucose(GLU SD), largest amplitude of glycemic excursion(LAGE), mean amplitude of glycemic excursion(MAGE), glycemic difference(GLU dif), and glycemic lability index(GLI)] and in-hospital mortality in patients with sepsis. The search period was from the inception of each database to July 9, 2025. Two reviewers independently screened the literature and extracted data. The Newcastle-Ottawa Scale was used to assess study quality, and Kappa coefficients were calculated to evaluate inter-rater agreement. Included studies were also appraised against the Strengthening the Reporting of Observational Studies in Epidemiology(STROBE) checklist. Meta-analyses were performed using RevMan 5.4. Results: A total of 25 studies involving 3 876 patients were included. Twenty-one cohort studies were analyzed by survival outcome(death vs survival), and four cohort studies were analyzed by the degree of glycemic variability(high vs. low variability). Meta-analysis showed that, compared with survivors, in-hospital non-survivors had significantly higher values of all glycemic variability metrics: coefficient of variation of glucose(GLU CV)(SMD=1.065, 95%CI 0.563-1.568, P<0.001), standard deviation of blood glucose(GLU SD)(MD=0.812, 95%CI 0.443-1.181, P<0.001), glycemic difference(GLU dif)(MD=1.152, 95%CI 0.688-1.616, P<0.001), largest amplitude of glycemic excursion(LAGE)(MD=2.725, 95%CI 1.162-4.288, P<0.001), mean amplitude of glycemic excursion(MAGE)(MD=0.287, 95%CI 0.176-0.397, P<0.001), and glycemic lability index(GLI)(SMD=1.938, 95%CI 0.467-3.410, P=0.010). Patients in the high glycemic variability group had a higher in-hospital mortality rate than those in the low variability group(OR=14.550, 95%CI 1.078-196.436, P=0.043). Subgroup analyses stratified by diabetes status and insulin use showed that among patients with diabetes or those receiving insulin therapy, GLU CV and GLU SD were significantly higher in the non-survivor group(all P<0.05). In patients without diabetes or not receiving insulin, these differences were not statistically significant(all P>0.05).Conclusion:Elevated glycemic variability, a simple and cost-effective indicator, is associated with an increased risk of in-hospital mortality in patients with sepsis, particularly in those with diabetes or requiring insulin therapy. Monitoring glycemic variability may facilitate early risk stratification and individualized intervention decisions.

参考文献：

[1] FLEISCHMANN-STRUZEK C,MELLHAMMAR L,ROSE N,et al.Incidence and mortality of hospital- and ICU-treated sepsis:results from an updated and expanded systematic review and meta-analysis[J]. Intensive Care Med,2020,46(8):1552-1562.
[2] SINGER M,DEUTSCHMAN C S,SEYMOUR C W,et al.The third international consensus definitions for sepsis and septic shock(sepsis-3)[J]. JAMA,2016,315(8):801-810.
[3] RUDD K E,JOHNSON S C,AGESA K M,et al.Global,regional,and national sepsis incidence and mortality,1990-2017:analysis for the Global Burden of Disease Study[J]. Lancet,2020,395(10219):200-211.
[4] CECCONI M,EVANS L,LEVY M,et al.Sepsis and septic shock[J]. Lancet,2018,392(10141):75-87.
[5] MAGEE F,BAILEY M,PILCHER D V,et al.Early glycemia and mortality in critically ill septic patients:interaction with insulin-treated diabetes[J]. J Crit Care,2018,45:170-177.
[6] 江华.危重症患者的应激性高血糖、营养治疗与血糖管理[J]. 中华糖尿病杂志,2015,7(2):71-72.
[7] PREECHASUK L,SUWANSAKSRI N,IPICHART N,et al.Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects[J]. J Crit Care,2017,38:319-323.
[8] 孙才智,仲伯蒙,沈华,等.6 h内血糖变异度对脓毒性休克患者短期预后的预测价值[J]. 中华危重病急救医学,2021,33(1):28-32.
[9] KRINSLEY J S,RULE P,PAPPY L,et al.The interaction of acute and chronic glycemia on the relationship of hyperglycemia,hypoglycemia,and glucose variability to mortality in the critically ill[J]. Crit Care Med,2020,48(12):1744-1751.
[10] 陈伟,沈琦,陈虞红.血糖变异系数对急诊脓毒症患者脓毒症相关性脑病的预测价值[J]. 中国急救医学,2024,44(9):815-821.
[11] 董蜜兰,罗业涛,刘文俊,等.血糖波动对危重患儿预后影响的前瞻性研究[J]. 重庆医科大学学报,2022,47(4):450-454.
[12] CHAO W C,TSENG C H,WU C L,et al.Higher glycemic variability within the first day of ICU admission is associated with increased 30-day mortality in ICU patients with sepsis[J]. Ann Intensive Care,2020,10(1):17.
[13] 张霖,周婉,陈剑.脓毒症糖代谢紊乱的发生机制及治疗[J]. 中华糖尿病杂志,2020,12(9):753-755.
[14] ATAMNA A,AYADA G,AKIROV A,et al.High blood glucose variability is associated with bacteremia and mortality in patients hospitalized with acute infection[J]. QJM,2019,112(2):101-106.
[15] ZHOU Z,SUN B,HUANG S,et al.Glycemic variability:adverse clinical outcomes and how to improve it[J]. Cardiovasc Diabetol,2020,19(1):102.
[16] SUN B,LUO Z,ZHOU J.Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications[J]. Cardiovasc Diabetol,2021,20(1):9.
[17] STROUP D F.Meta-analysis of observational studies in Epidemiology:a proposal for reporting[J]. JAMA,2000,283(15):2008.
[18] STANG A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol,2010,25(9):603-605.
[19] VON ELM E,ALTMAN D G,EGGER M,et al.The strengthening the reporting of observational studies in epidemiology(STROBE) statement:guidelines for reporting observational studies[J]. Lancet,2007,370(9596):1453-1457.
[20] HIGGINS J P T,THOMPSON S G.Quantifying heterogeneity in a meta-analysis[J]. Stat Med,2002,21(11):1539-1558.
[21] 王建峰,王哲.血糖波动对非糖尿病脓毒症患者病死率影响的研究[J]. 临床研究,2016,24(7):194.
[22] PRAKASH P,SETHI P,VIKRAM N,et al.Association of glycemic variability with outcomes in non-diabetic sepsis patients:a prospective observational study[J]. Indian J Crit Care Med,2025,29(1):27-35.
[23] LEUNG C H,LIU C P.Diabetic status and the relationship of blood glucose to mortality in adults with carbapenem-resistant Acinetobacter baumannii complex bacteremia[J]. J Microbiol Immunol Infect,2019,52(4):654-662.
[24] GUNAWAN B,PURWANTA R S,JENNIFE R,et al.Glycemic variability as an independent predictor of 30-day mortality in type 2 diabetes individuals with sepsis in the intensive care unit[J]. Clin Diabetol,2025,14(1):18-25.
[25] 刘海洋,高君武.早期血糖不稳定指数及乳酸清除率对感染性休克患者预后的评估价值[J]. 中国中西医结合急救杂志,2020,27(1):68-71.
[26] 龙蕾,李青,易卓卓.血糖波动对2型糖尿病合并脓毒症患者预后的影响[J]. 湖南师范大学学报(医学版),2024,21(1):95-97,114.
[27] 曾建琼,程青虹,王桂萍.老年脓毒症患者血糖变异度与预后的相关性[J]. 中国老年学杂志,2017,37(10):2520-2522.
[28] 曾泳萍.血糖变异指标对脓毒症患者预后的评估价值分析[J]. 糖尿病新世界,2019,22(22):31-32.
[29] 褚晨,杨碧宁.血糖波动对脓毒性休克患者预后的评估价值[J]. 实用妇科内分泌电子杂志,2020,7(27):186-187,191.
[30] 冯慧远,胡敦重,崔云亮,等.不同血糖变异指标在脓毒症患者预后评估中的对比研究[J]. 中国急救医学,2015(S1):9-11.
[31] 韩旭东,黄晓英,葛志华,等.脓毒症患者血糖变异度与预后的相关性研究[J/OL]. 中华危重症医学杂志(电子版),2011,4(3):168-172.
[32] 厉丹瑜,姚佳丽,童洪杰,等.中性粒细胞/淋巴细胞比值、血糖变异度对脓毒症患者预后的预测价值[J]. 中国现代医生,2025,63(5):53-56.
[33] 路紫贺.血糖波动对脓毒症患者预后影响的临床研究[D]. 承德:承德医学院,2022.
[34] 吕瑶瑶,王莹,焦海妮,等.糖代谢紊乱与重症肺炎合并脓毒症患者病情及预后的关系[J]. 疑难病杂志,2021,20(2):148-152,157.
[35] 罗雯蓉.血糖变异性血乳酸清除率与术后脓毒血症患者预后的临床研究[J]. 山西医药杂志,2016,45(23):2800-2802.
[36] 舒海林,施云弟,陆通安.血糖水平及血糖变异度对ICU成年脓毒症患者预后的影响[J]. 医学理论与实践,2023,36(12):2087-2089.
[37] 苏杭.血糖变异系数与糖尿病合并脓毒症患者预后相关性的研究[D]. 天津:天津医科大学,2016.
[38] 徐伟干,符岳,霍健杨,等.老年脓毒症合并应激性高血糖患者血糖变异性与近期预后的相关性[J]. 广西医学,2021,43(5):537-540,544.
[39] 杨旦,王金柱,郑漾.非糖尿病脓毒症患者入院6 h血糖变异度的临床分析[J]. 现代实用医学,2024,36(1):85-88.
[40] 周浩,黄中伟.脓毒症患者血糖变异与疾病严重程度、预后的相关性[J]. 中国老年学杂志,2025,45(10):2353-2357.
[41] 朱妮妮.血糖变异性对脓毒症预后影响的临床研究[D]. 昆明:昆明医科大学,2012.
[42] 杨宇宁.脓毒症患者血糖与预后关系的前瞻性观察研究[J]. 中外医疗,2013,32(28):104-105.
[43] 周启,马新华,徐道妙.综合ICU内脓毒症患者低血糖与预后的相关性研究[J]. 中国卫生检验杂志,2017,27(6):842-844,847.
[44] 葛志华,韩旭东,黄晓英,等.脓毒症患者早期血糖波动与预后的相关性研究[J]. 中国急救医学,2013,33(7):592-595.
[45] ZHANG H,DONG N,YAO Y.Optimal strategy for treatment of sepsis based on the host inflammatory reaction and immune response[J]. J Intensive Med,2024,4(2):175-180.
[46] LA VIA L,SANGIORGIO G,STEFANI S,et al.The global burden of sepsis and septic shock[J]. Epidemiologia,2024,5(3):456-478.
[47] LAKSHMIKANTH C L,JACOB S P,CHAITHRA V H,et al.Sepsis:in search of cure[J]. Inflamm Res,2016,65(8):587-602.
[48] 刘宽,黄文娟,黄祺,等.脓毒症时糖代谢紊乱的逆转措施研究进展[J]. 中华危重病急救医学,2018,30(6):616-618.
[49] RISSO A,MERCURI F,QUAGLIARO L,et al.Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture[J]. Am J Physiol Endocrinol Metab,2001,281(5):E924-E930.
[50] SUH S W,GUM E T,HAMBY A M,et al.Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase[J]. J Clin Invest,2007,117(4):910-918.
[51] QUAGLIARO L,PICONI L,ASSALONI R,et al.Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells:the role of protein kinase C and NAD(P)H-oxidase activation[J]. Diabetes,2003,52(11):2795-2804.
[52] 刘贝贝,朱红斌,仲丽娟,等.“龙头医院辐射基层健康管理模式”下的2型糖尿病患者代谢控制状况的分析[J]. 现代医学,2024,52(5):732-737.
[53] LI X,ZHANG D,CHEN Y,et al.Acute glycemic variability and risk of mortality in patients with sepsis:a meta-analysis[J]. Diabetol Metab Syndr,2022,14(1):59.
[54] FABBRI A,MARCHESINI G,BENAZZI B,et al.Stress hyperglycemia and mortality in subjects with diabetes and sepsis[J]. Crit Care Explor,2020,2(7):e0152.
[55] WANG J,ZHU C K,YU J Q,et al.Hypoglycemia and mortality in sepsis patients:a systematic review and meta-analysis[J]. Heart Lung,2021,50(6):933-940.
[56] CHEN L,SUN W,LIU Y,et al.Association of early-phase in-hospital glycemic fluctuation with mortality in adult patients with coronavirus disease 2019[J]. Diabetes Care,2021,44(4):865-873.
[57] WANG J,WANG L L,YANG Y M,et al.Impact of acute glycemic variability on short-term outcomes in patients with ST-segment elevation myocardial infarction:a multicenter population-based study[J]. Cardiovasc Diabetol,2024,23(1):155.
[58] LIN J,CAI C,XIE Y,et al.Acute glycemic variability and mortality of patients with acute stroke:a meta-analysis[J]. Diabetol Metab Syndr,2022,14(1):69.
[59] LI W,WANG Y,ZHONG G.Glycemic variability and the risk of atrial fibrillation:a meta-analysis[J]. Front Endocrinol,2023,14:1126581.
[60] EMGIN Ö,YAVUZ M,ŞAHIN A,et al.The association between glycemic variability and mortality in critically ill patients:a multicenter prospective observational study[J]. J Clin Med,2024,13(22):6939.
[61] KRUYT N D,VAN WESTERLOO D J,DEVRIES J H.Stress-induced hyperglycemia in healthy bungee jumpers without diabetes due to decreased pancreatic β-cell function and increased insulin resistance[J]. Diabetes Technol Ther,2012,14(4):311-314.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录