文献类型：期刊文献

中文题名：血清EPS-15相互作用蛋白1与2型糖尿病患者视网膜病变的关联性:基于亚组分析的异质性

英文题名：Association between serum EPS-15 interacting protein 1 and type 2 diabetic retinopathy:a subgroup-based heterogeneity analysis

作者：刘芊[1];贾巧芳[1];毛华博[1];邹艳[1];王钰鼎[1];王伊楠[1];权金星[2]

第一作者：刘芊

机构：[1]甘肃中医药大学第一临床医学院,兰州730000;[2]甘肃省人民医院内分泌科,兰州730000

第一机构：甘肃中医药大学临床医学院

年份：2026

卷号：18

期号：3

起止页码：228

中文期刊名：中华糖尿病杂志

外文期刊名：CHINESE JOURNAL OF DIABETES MELLITUS

收录：;北大核心:【北大核心2023】；

基金：甘肃省科技计划(25YFFA047)。

语种：中文

中文关键词：糖尿病,2型;糖尿病视网膜病变;EPS-15相互作用蛋白1;疾病严重程度

外文关键词：Diabetes mellitus,type 2;Diabetic retinopathy;EPS-15-interacting protein 1;Disease severity grading

摘要：目的探讨血清EPS-15相互作用蛋白1(EPSIN1)与2型糖尿病(T2DM)患者糖尿病视网膜病变(DR)的关联及人群异质性。方法本研究为横断面研究。参与者来源于两个独立的横断面数据集,包括发现集与验证集。发现集:连续纳入2024年3月至2025年3月于甘肃省人民医院内分泌科住院的268例T2DM患者,同期纳入该院137例健康体检者作为正常对照(NC)组。将T2DM患者分为单纯T2DM组(144例)和DR组(124例);DR组再分为非增殖期DR(NPDR)组(64例)和增殖期DR(PDR)组(60例)。验证集:为了评估EPSIN1在T2DM患者内部的区分能力,自2025年4至10月纳入同科室T2DM患者102例。检测发现集和验证集T2DM患者血清EPSIN1及以下临床生化指标:甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血肌酐(Scr)、血尿酸(SUA)、超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、空腹血糖(FPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA 1c)。计算估算的肾小球滤过率(eGFR)和稳态模型评估胰岛素抵抗指数(HOMA-IR)。采用Pearson相关分析法分析EPSIN1与一般资料、生化指标的相关性,单因素及多因素logistic逐步回归分析法分析DR的影响因素,受试者工作特征(ROC)曲线评估EPSIN1对DR的诊断效能,并通过亚组分析及交互作用检验探索异质性。结果在发现集中,EPSIN1与年龄(r=0.21)、病程(r=0.43)、SUA(r=0.27)呈正相关,与eGFR呈负相关(r=-0.25)(均P<0.001)。多因素logistic回归分析结果显示,SUA(OR=1.02,95%CI 1.01~1.03)、eGFR(OR=0.96,95%CI 0.92~0.98)、EPSIN1(OR=1.05,95%CI 1.04~1.07)是DR的影响因素。EPSIN1随DR进展梯度升高(F=366.867,P<0.001)。ROC曲线显示,EPSIN1诊断DR的曲线下面积(AUC)为0.82(95%CI 0.75~0.89),灵敏度80.90%,特异度82.10%,最佳截断值519.76 ng/L。该效能在验证集中得到确认(AUC=0.80,95%CI 0.69~0.90)。亚组分析显示,EPSIN1与DR的关联在女性(OR=1.08,95%CI 1.04~1.11)、病程≤7年(OR=1.08,95%CI 1.04~1.13)、年龄≥55岁(OR=1.08,95%CI 1.04~1.13)及HbA 1c<8.58%(OR=1.09,95%CI 1.04~1.13)的T2DM患者中效应更强。结论血清EPSIN1是T2DM患者发生DR的影响因素,与DR严重程度呈正相关。EPSIN对于DR的诊断价值良好且经独立队列验证,在女性、病程≤7年、年龄≥55岁及HbA 1c<8.58%的T2DM患者中EPSIN1与DR的关联更显著。
ObjectiveTo investigate the association between serum EPS-15-interacting protein 1(EPSIN1)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM),and to explore population heterogeneity.MethodsThis was a cross-sectional study.Participants were from two independent cross-sectional datasets(a discovery set and a validation set).Discovery set:from March 2024 to March 2025,a total of 268 hospitalized T2DM patients from the Department of Endocrinology of Gansu Provincial Hospital were consecutively enrolled.During the same period,137 healthy individuals from the hospital′s health check-up center were included as a normal control(NC)group.T2DM patients were divided into the T2DM-only group(144 cases)and the DR group(124 cases).The DR group was further divided into non-proliferative DR(NPDR,64 cases)and proliferative DR(PDR,60 cases)subgroups.Validation set:to evaluate the discriminative ability of EPSIN1 among T2DM patients,102 T2DM patients from the same department were enrolled from April to October 2025.Serum levels of EPSIN1 and the following clinical biochemical indicators were measured:triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(Scr),serum uric acid(SUA),high-sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),fasting plasma glucose(FPG),fasting insulin(FINS),and glycated hemoglobin A 1c(HbA 1c).The estimated glomerular filtration rate(eGFR)was calculated using a formula,and the homeostasis model assessment of insulin resistance(HOMA-IR)was computed.Pearson correlation analysis was used to examine the associations between EPSIN1 and general characteristics/biochemical indicators.Univariate and multivariate logistic stepwise regression analyses were performed to identify influencing factors for DR.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of EPSIN1 for DR.Subgroup analysis and interaction tests were conducted to explore heterogeneity.ResultsIn the discovery set,EPSIN1 levels were positively correlated with age(r=0.21),diabetes duration(r=0.43),and SUA(r=0.27),and negatively correlated with eGFR(r=-0.25)(all P<0.001).Multivariate logistic regression showed that SUA(OR=1.02,95%CI 1.01-1.03),eGFR(OR=0.96,95%CI 0.92-0.98),and EPSIN1(OR=1.05,95%CI 1.04-1.07)were influencing factors for DR.EPSIN1 levels increased progressively with DR progression(F=366.867,P<0.001).The ROC curve showed that the area under the curve(AUC)of EPSIN1 for diagnosing DR was 0.82(95%CI 0.75-0.89),with a sensitivity of 80.90%,a specificity of 82.10%,and an optimal cutoff value of 519.76 ng/L.This efficacy was confirmed in the validation set(AUC=0.80,95%CI 0.69-0.90).Subgroup analysis revealed that the association between EPSIN1 and DR was stronger in females(OR=1.08,95%CI 1.04-1.11),patients with diabetes duration≤7 years(OR=1.08,95%CI 1.04-1.13),aged≥55 years(OR=1.08,95%CI 1.04-1.13),and patients with HbA 1c<8.58%(OR=1.09,95%CI 1.04-1.13).ConclusionsSerum EPSIN1 is an influencing factor for DR in T2DM patients and is positively correlated with DR severity.EPSIN1 demonstrates good diagnostic performance,which was validated in an independent set.Moreover,the association between EPSIN1 and DR is more significant in female T2DM patients,those with a disease duration≤7 years,aged≥55 years,and with HbA 1c<8.58%.