摘要
目的 探讨2型糖尿病肾病(T2DN)患者血清miR-92b-5p及高迁移率族蛋白Box1(HMGB1)水平的变化及其临床意义.方法 回顾性选取2022年1月至2024年1月大庆龙南医院(齐齐哈尔医学院第五附属医院)收治入院的150例2型糖尿病(T2DM)患者,参考有无合并肾病分为T2DM组(n=75)与T2DN组(n=75),并将同期入院进行体检的75名健康者设为健康组.比较3组研究对象的3组一般资料(性别、年龄、体重指数、吸烟史、饮酒史、高血压史)与常规化验指标[低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯、总胆固醇、肌酐、24 h尿蛋白(24 hpro)、空腹血糖、糖化血红蛋白(HbA1c)、肾小球滤过率(GFR)]、血清HMGB1、miR-92b-5p水平;采用多因素Logistic回归分析影响T2DM进展至T2DN的危险因素;采用Pearson分析GFR、24 hpro与HMGB1、miR-92b-5p的相关性;采用受试者操作特征(ROC)曲线评估HMGB1、miR-92b-5p单独及联合检测预测T2DN的价值.结果 3组研究对象的性别、年龄、体重指数、吸烟史、饮酒史、高血压史及LDL-C、HDL-C、甘油三酯、总胆固醇水平比较,差异均无统计学意义(P>0.05);3组研究对象的肌酐、24 hpro、空腹血糖、HbA1c、GFR、HMGB1、miR-92b-5p比较,差异均有统计学意义(P<0.05).多因素Logistic回归分析结果显示,T2DM进展至T2DN这一过程中GFR、miR-92b-5p下降与24 hpro、HMGB1上升为独立危险因素(P<0.05).相关性分析结果显示,T2DM患者HMGB1与估算GFR呈负相关(P<0.05),与 24 hpro 呈正相关(P<0.05);miR-92b-5p 与 GFR 呈正相关(P<0.05),与 24 hpro、HMGB1呈负相关(P<0.05).ROC分析结果显示,T2DN预测中单一 HMGB1检测ROC曲线下面积(AUC)为0.801(95%CI:0.736~0.859),单一 miR-92b-5p 检测 AUC 为 0.753(95%CI:0.687~0.820),联合检测 AUC 为 0.857(95%CI:0.799~0.907);T2DN 预测中 HMGB1 联合 miR-92b-5p 检测的 AUC 大于 HMGB1 或者 miR-92b-5p单一检测.结论 T2DM进展至T2DN的过程中miR-92b-5p水平下降、HMGB1水平上升起着关键性作用,属于独立危险因素,早期阶段联合测定血清HMGB1、miR-92b-5p水平可辅助诊断T2DN.
Abstract
Objective To investigate the changes and dinical significance of serum levels of miR-92b-5p and high mobility group pro-tein Box1(HMGB1)in patients with type 2 diabetic nephropathy(T2DN).Methods A total of 150 patients with type 2 diabetes mellitus(T2DM)admitted to Daqing Longnan Hospital(The Fifth Affiliated Hospital of Qiqihar Medical College)from January 2022 to January 2024 were retrospectively selected and divided into the T2DM group(n=75)and the T2DN group(n=75)according to whether they were complicated with kidney disease.Seventy-five healthy patients admitted for physical examination during the same period were divided into the healthy group.The general data(gender,age,body mass index,smoking history,drinking history,hypertension history)and routine laboratory indexes[low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglyceride,total cholesterol,creatinine,24 h urine protein(24 hpro),fasting blood glucose,glycosylated hemoglobin(HbA1c),glomerular filtration rate(GFR)],serum HMGB1 and miR-92b-5p levels were compared among the three groups.The risk factors affecting the progression of T2DM to T2DN was analyzed by Multivariate Logistic regression analysis.The correlation between GFR,24 hpro and HMGB1,miR-92b-5p was analyzed by Pearson analysis.The value of HMGB1,miR-92b-5p alone and combined detection in predicting T2DN was evaluated by the receiver operating characteristic(ROC)curve.Results There were no significant differences in gender,age,body mass index,smoking history,drinking history,hypertension history,LDL-C,HDL-C,triglyceride and total cholesterol levels among the three groups(P>0.05).There were statistically significant differences in creati-nine,24 hpro,fasting blood glucose,HbA1c,GFR,HMGB1 and miR-92 b-5p among the three groups(P<0.05).Multivariate Logistic re-gression analysis showed that the decrease of GFR and miR-92b-5p and the increase of 24 hpro and HMGB1 were independent risk factors in the process of T2DM progressing to T2DN(P<0.05).Correlation analysis showed that HMGB1 in T2 DM patients was negatively correlated with es-timated GFR(P<0.05)and positively correlated with 24 hpro(P<0.05).MiR-92b-5p was positively correlated with GFR(P<0.05),and negatively correlated with 24 hpro and HMGB1(P<0.05).The results of ROC analysis showed that the area under the ROC curve(AUC)of single HMGB1 detection in T2DN prediction was 0.801(95%CI:0.736-0.859),the AUC of single miR-92b-5p detection was 0.753(95%CI:0.687-0.820),and the AUC of combined detection was 0.857(95%CI:0.799-0.907).The AUC of HMGB1 combined with miR-92b-5p in T2DN prediction was greater than that of HMGB1 or miR-92b-5p alone.Conclusion The decrease of miR-92b-5p and the increase of HMGB1 play a key role in the progression of T2DM to T2DN,and they are independent risk factors.Combined determination of HMGB1 and miR-92b-5p at the early stage can assist in the diagnosis of T2DN.