肠道菌群及血清sdLDL-C、LPS与糖尿病视网膜病变的相关性研究

Correlation Between Intestinal Flora, Serum sdLDL-C, LPS, and Diabetic Retinopathy

摘要

目的 探讨肠道菌群、血清小而密低密度脂蛋白胆固醇（small and dense low-density lipoprotein cholesterol，sdLDL-C）、脂多糖（lipopolysaccharide，LPS）与糖尿病视网膜病变（diabetic retinopathy，DR）的相关性。方法 选取2021年10月至2023年10月就诊于喀什地区第一人民医院的102例2型糖尿病（type 2 diabetes，T2DM）患者，根据是否合并视网膜病变分为非DR组（n = 72）与DR组（n = 30）。比较两组一般资料、实验室指标、肠道菌群及血清sdLDL-C、LPS水平；多因素Logistic回归分析DR的影响因素；斯皮尔曼秩相关系数分析（Spearman's correlation analysis，Spearman）秩相关分析肠道菌群、血清sdLDL-C、LPS与DR相关性；受试者工作特征曲线（receiver operating characteristic curve，ROC）评估血清sdLDL-C、LPS水平对DR的预测效能。结果 与非DR组比较，DR组拟杆菌属（31.28±7.70）含量显著升高（t = 9.905，P < 0.05）；血清sdLDL-C（1.51±0.37）mmol/L、LPS（117.45±9.39）pg/mL水平显著升高（t = 4.422、25.160，P < 0.05）；双歧杆菌属和普雷沃菌属含量显著降低（t = 19.886、11.883，P < 0.05）；乳酸杆菌属、普拉梭菌属、肠球菌属、直肠真杆菌属、韦荣球菌属、柔嫩梭菌属、罗氏菌属差异无统计学意义（P > 0.05）。单因素分析显示，DR组糖尿病病程、收缩压（systolic pressure，SBP）、血肌酐（Serum creatinine，SCr）、空腹血糖（fasting blood glucose，FPG）、三酰甘油（triglyceride，TG）、低密度脂蛋白胆固醇（low density lipoprotein-C，LDL-C）、糖化血红蛋白（glycosylated hemoglobin，HbA1c）及高血压史占比显著高于非DR组（P < 0.05）；年龄、体质量指数（body mass index，BMI）、性别、舒张压（diastolic pressure，DBP）、吸烟史占比、饮酒史占比、总胆固醇（total cholesterol，TC）、高密度脂蛋白胆固醇（high density lipoprotein-C，HDL-C）差异无统计学意义（P > 0.05）。多因素Logistic回归显示，糖尿病病程、SCr、TG、HbA1c、sdLDL-C、LPS、拟杆菌属升高为DR的危险因素（P < 0.05），普雷沃菌属降低为DR的保护因素（P < 0.05）。相关性分析显示，拟杆菌属含量、sdLDL-C、LPS水平与DR呈正相关（P < 0.05）；双歧杆菌属、普雷沃菌属含量与DR呈负相关（均P < 0.05）。ROC曲线显示，sdLDL-C+LPS联合预测DR的AUC为0.811（95%CI: 0.719～0.893），灵敏度为86.72%，特异度为79.83%。结论 T2DM合并DR患者存在肠道菌群紊乱及血清sdLDL-C、LPS水平异常升高，sdLDL-C、LPS、拟杆菌属为DR的危险因素，普雷沃菌属为DR的保护因素，sdLDL-C联合LPS对DR有一定预测作用。

Abstract

Objective To explore the correlations between gut microbiota, serum small and dense low-density lipoprotein cholesterol (sdLDL-C), lipopolysaccharide (LPS), and diabetic retinopathy (DR). Methods A total of 102 patients with type 2 diabetes (T2DM) who attended the First People's Hospital of Kashgar from October 2021 to October 2023 were selected. According to the presence or absence of diabetic retinopathy, patients were divided into non-DR group (n = 72) and DR group (n = 30). General information, laboratory indices, intestinal flora, and serum levels of sdLDL-C and LPS were compared between the two groups. Multivariate Logistic regression analysis was conducted to identify risk factors for DR. Spearman's correlation analysis was used to analyze the rank correlation between intestinal flora, serum sdLDL-C, LPS and DR. Receiver operating characteristic curves (ROC) was used to evaluate the predictive performance of serum sdLDL-C and LPS levels for DR. Results Compared with the non-DR group, the DR group exhibited significantly elevated Bacteroides abundance (31.28±7.70) (t = 9.905, P < 0.05); significantly elevated serum sdLDL-C (1.51±0.37) mmol/L and LPS (117.45±9.39) pg/mL levels (t = 4.422, 25.160, P < 0.05); and significantly reduced Bifidobacterium and Prevotella abundance (t = 19.886, 11.883, P < 0.05). There were no significant differences in Lactobacillus, Plasmodicoccus, Enterococcus, Eubacterium rectale, Veillonella, Clostridium tenellum, and Roseburia species (P > 0.05). Univariate analysis showed that the duration of diabetes, systolic pressure (SBP), serum creatinine (SCr), fasting blood glucose (FPG), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (HbA1c), and history of hypertension in the DR group were significantly higher than those in the non-DR group (P < 0.05). Age, body mass index (BMI), gender, diastolic pressure (DBP), smoking history, drinking history, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) showed no statistically significant difference (P > 0.05). Multivariate Logistic regression showed that the duration of diabetes, SCr, TG, HbA1c, sdLDL-C, LPS, and elevated Bacteroides were risk factors for DR (P < 0.05), while reduced Prevotella was a protective factor for DR (P < 0.05). Correlation analysis showed that Bacteroides abundance, sdLDL-C, and LPS levels were positively correlated with DR (P < 0.05); while Bifidobacterium and Prevotella abundance were negatively correlated with DR (P < 0.05). ROC curve showed that combination of sdLDL-C and LPS had an area under the curve (AUC) (95%CI: 0.719～0.893), with a sensitivity of 86.72% and a specificity of 79.83%. Conclusion Patients with T2DM complicated by DR exhibit gut dysbiosis and abnormally elevated serum sdLDL-C and LPS levels. sdLDL-C, LPS, and elevated Bacteroides are risk factors for DR, while Prevotella is a protective factor.

关键词

2型糖尿病 / 糖尿病视网膜病变 / 肠道菌群 / 小而密低密度脂蛋白胆固醇 / 脂多糖 / 相关性

Key words

Type 2 diabetes / Diabetic retinopathy / Intestinal flora / Small and dense LDL cholesterol / Lipopolysaccharide / Relevance

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基金资助

国家自然科学基金(81870544)