作者：陆水英，汤之明，陈力行，刘琳

单位：

1.肇庆医学高等专科学校2.广东省肇庆市第一人民医院CCU

Units：

1.Zhaoqing Medical College, Zhaoqing 526000, China 2.CCU, the First People's Hospital of Zhaoqing, Zhaoqing 526000, China

关键词：

糖尿病; 老年人; 胃肠道微生物组; 肠道菌群; 主要不良心血管事件;

Keywords：

Diabetes mellitus; Aged; Gastrointestinal microbiome; Intestinal flora; Major adverse cardiac events

CLC：

DOI：

10.12114/j.issn.1008-5971.2023.00.187

Funds：

广东省高职教育医药卫生类专业教指委教改课题（2019LX012）；广东省医学科学技术研究基金项目（B2019253）

摘要：

目的 探讨肠道菌群易位与老年糖尿病患者发生主要不良心血管事件(MACE)的关系。方法 选取2019年1月至2021年1月在肇庆市第一人民医院治疗的100例老年糖尿病患者作为研究对象，根据随访期间患者是否发生MACE将其分为MACE(+)组23例和MACE(-)组77例。另选取同期在肇庆市第一人民医院接受健康体检的非糖尿病者50例作为对照组。比较对照组、MACE(-)组及MACE(+)组操作分类单元(OTU)总数、香农指数及血浆肠道菌群百分比。比较MACE(-)组和MACE(+)组临床资料、实验室检查指标及左心室射血分数(LVEF)。老年糖尿病患者发生MACE的影响因素分析采用多因素Cox比例风险回归分析，绘制ROC曲线以评估Δ三甲胺N-氧化物(TMAO)、ΔD-乳酸、Z评分(基于ΔTMAO和ΔD-乳酸构建的新变量)及Z评分+超敏C反应蛋白(hs-CRP)+CD14+CD16+单核细胞计数对老年糖尿病患者发生MACE的预测价值。ΔTMAO和ΔD-乳酸与CD14+CD16+单核细胞计数的相关性分析采用Spearman秩相关分析。结果 MACE(+)组OTU总数、香农指数及血浆肠道菌群百分比均高于对照组和MACE(-)组(P<0.05)。主坐标分析结果显示，MACE(+)组血液细菌特征与对照组或MACE(-)组的血液细菌特征明显分开(P值均<0.001)。MACE(+)组hs-CRP、CD14+CD16+单核细胞计数、TMAO、D-乳酸、ΔCD14+CD16+单核细胞计数、ΔTMAO、ΔD-乳酸及Z评分高于MACE(-)组，LVEF低于MACE(-)组(P<0.05)。多因素Cox比例风险回归分析结果显示，hs-CRP、CD14+CD16+单核细胞计数、Z评分是老年糖尿病患者发生MACE的独立影响因素(P<0.05)。ROC曲线分析结果显示，ΔTMAO、ΔD-乳酸、Z评分、Z评分+hs-CRP+CD14+CD16+单核细胞计数预测老年糖尿病患者发生MACE的AUC分别为0.647[95%CI(0.533,0.761)]、0.630[95%CI(0.527,0.725)、0.681[95%CI(0.567,0.794)、0.822[95%CI(0.738,0.906)。Spearman秩相关分析结果显示，ΔTMAO与老年糖尿病患者ΔCD14+CD16+单核细胞计数呈正相关(rs=0.200,P=0.047)，ΔTMAO和ΔD-乳酸与MACE(+)组患者ΔCD14+CD16+单核细胞计数呈正相关(rs值分别为0.322、0.290,P值分别为0.028、0.048)。结论 发生MACE的老年糖尿病患者全身微生物组多样性增加，血浆肠道菌群百分比升高，肠道菌群易位是老年糖尿病患者发生MACE的影响因素；与ΔTMAO、ΔD-乳酸、Z评分单独预测相比，Z评分+hs-CRP+CD14+CD16+单核细胞计数预测老年糖尿病患者发生MACE的价值较高。

Abstract：

　Objective To explore the relationship between intestinal flora translocation and major adverse cardiovascular events (MACE) in elderly patients with diabetic mellitus. Methods A total of 100 elderly patients with diabetic mellitus treated in the First People's Hospital of Zhaoqing from January 2019 to January 2021 were selected as the research objects, and they were divided into MACE (+) group (23 cases) and MACE (-) group (77 cases) according to whether the patients developed MACE during the follow-up period. In addition, 50 non-diabetic subjects who received health examination in the First People's Hospital of Zhaoqing during the same period were selected as the control group. The total number of operational taxonomic units (OTU) , Shannon index and percentage of intestinal flora in plasma were compared among control group, MACE (-) group and MACE (+) group. The clinical data, laboratory examination indexes and left ventricular ejection fraction (LVEF) were compared between MACE (-) group and MACE (+) group. Multivariate Cox proportional hazard regression analysis was used to analyze the influencing factors of MACE in elderly patients with diabetic mellitus, and ROC curve was drawn to evaluate the predictive value of Δtrimethylamine N-oxide (TMAO) , ΔD-lactic acid, Z score (new variable based on ΔTMAO and ΔD?lactic acid) and Z score+high-sensitivity C-reactive protein (hs-CRP) +CD14+ CD16+ monocyte count in predicting MACE in elderly patients with diabetic mellitus. Spearman rank correlation analysis was used to analyze the correlation between ΔTMAO and ΔD-lactic acid and ΔCD14+ CD16+ monocyte count. Results The total number of OTU, Shannon index and percentage of intestinal flora in plasma in MACE (+) group were higher than those in control group and MACE (-) group (P < 0.05) . The results of principal coordinate analysis showed that the blood bacterial characteristics of MACE (+) group were obviously different from those of control group or MACE (-) group (both P values were < 0.001) . hs-CRP, CD14+ CD16+ monocyte count, TMAO, D-lactic acid, ΔCD14+ CD16+ monocyte count, ΔTMAO, ΔD-lactic acid and Z score in MACE (+) group were higher than those in MACE (-) group, and LVEF was lower than that in MACE (-) group (P < 0.05) . Multivariate Cox proportional hazard regression analysis results showed that hs-CRP, CD14+ CD16+ monocyte count and Z score were independent influencing factors of MACE in elderly patients with diabetic mellitus (P < 0.05) . The ROC curve analysis results showed that the AUC of ΔTMAO, ΔD-lactic acid, Z score, Z score+hs-CRP+CD14+ CD16+ monocyte count in predicting the MACE in elderly patients with diabetic mellitus were 0.647 [95%CI (0.533, 0.761) ] , 0.630 [95%CI (0.527, 0.725) ] , 0.681 [95%CI (0.567, 0.794) ] , 0.822 [95%CI (0.738, 0.906) ] , respectively. Spearman rank correlation analysis results showed that ΔTMAO was positively correlated with ΔCD14+ CD16+ monocyte count in elderly patients with diabetic mellitus (rs=0.200, P=0.047) , and ΔTMAO and ΔD-lactic acid were positively correlated with ΔCD14+ CD16+ monocyte count in patients in MACE (+) group (rs values were 0.322, 0.290, P values were 0.028, 0.048, respectively) . Conclusion In elderly diabetic meiiltus patients with MACE, the systemic microbial diversity and the percentage of intestinal flora in plasma increase, and the translocation of intestinal flora is the influencing factor of MACE in elderly patients with diabetic mellitus. Compared with ΔTMAO, ΔD-lactic acid and Z score alone, Z score+hs-CRP+ CD14+ CD16+ monocyte count are more valuable in predicting the MACE in elderly patients with diabetic mellitus.

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