外周血β2微球蛋白、TFF3、Lp-PLA2对老年2型糖尿病患者早期肾功能损害及蛋白尿进展的评估价值

Evaluation value of peripheral blood β2-microglobulin, TFF3, and Lp-PLA2 in assessing early renal impairment and proteinuria progression in elderly patients with type 2 diabetes mellitus

摘要:

目的 分析外周血β2微球蛋白、三叶因子3（TFF3）、脂蛋白相关磷脂酶A2（Lp-PLA2）对老年2型糖尿病患者早期肾功能损害及蛋白尿进展的价值。方法 选择2021年3月—2024年5月邯郸市第一医院收治的97例老年2型糖尿病患者，根据Mogensen糖尿病肾病（DN）分期标准分为Ⅲ期组（35例）、Ⅳ期组（20例）、Ⅴ期组（11例）及非DN组（31例）。比较早期肾功能损害患者与非DN患者血清β2微球蛋白、TFF3、Lp-PLA2水平。采用Spearman法分析血清β2微球蛋白、TFF3、Lp-PLA2与老年2型糖尿病患者早期肾功能损害的相关性。根据老年2型糖尿病患者是否发生蛋白尿进展分为发生组（23例）与非发生组（74例）。多因素一般Logistic回归模型分析老年2型糖尿病患者发生蛋白尿进展的影响因素，绘制受试者工作特征（ROC）曲线评估β2微球蛋白、TFF3、Lp-PLA2的预测价值。结果 Ⅴ期组血清β2微球蛋白、TFF3、Lp-PLA2水平均高于Ⅲ期组、Ⅳ期组及非DN组（P <0.05），Ⅳ期组血清β2微球蛋白、TFF3和Lp-PLA2水平均高于Ⅲ期组和非DN组（P <0.05），Ⅲ期组血清β2微球蛋白、TFF3和Lp-PLA2水平高于非DN组（P <0.05）。Spearman相关性分析结果显示，血清β2微球蛋白、TFF3、Lp-PLA2与老年2型糖尿病患者早期肾功能损害均呈正相关（r_s = 0.573、0.625和0.594，P <0.05）。发生组二甲双胍使用率、血肌酐、血清β2微球蛋白、TFF3和Lp-PLA2水平均高于非发生组（P <0.05）。多因素一般Logistic回归分析结果显示，使用二甲双胍［O^R =4.821（95% CI：2.119，10.967）］、血清β2微球蛋白水平高［O^R =5.217（95% CI：2.294，11.869）］、血清TFF3水平高［O^R =4.112（95% CI：1.808，9.355）］、血清Lp-PLA2水平高［O^R =3.777（95% CI：1.660，8.593）］均为老年2型糖尿病患者发生蛋白尿进展的危险因素（P <0.05）。ROC曲线分析结果显示，血清β2微球蛋白、TFF3、Lp-PLA2水平及三者联合预测老年2型糖尿病患者发生蛋白尿进展的敏感性分别为78.26%（95% CI：0.725，0.874）、82.61%（95% CI：0.818，0.935）、91.30%（95% CI：0.856，0.991）、91.30%（95% CI：0.851，0.996）；特异性分别为85.14%（95% CI：0.783，0.961）、83.78%（95% CI：0.764，0.946）、72.97%（95% CI：0.654，0.816）、93.24%（95% CI：0.883，0.998）；曲线下面积分别为0.799（95% CI：0.682，0.915）、0.843（95% CI：0.721，0.967）、0.796（95% CI：0.679，0.912）、0.909（95% CI：0.778，1.043），联合预测价值更高。结论 血清β2微球蛋白、TFF3、Lp-PLA2水平与老年2型糖尿病患者早期肾功能损害均有相关性，三者在预测老年2型糖尿病患者蛋白尿进展中具有重要价值，且三者联合的预测价值更高。

Abstract:

Objective To evaluate the value of peripheral blood β2-microglobulin (β2-m), trefoil factor 3 (TFF3), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in assessing early renal function impairment and proteinuria progression in elderly patients with type 2 diabetes mellitus (T2DM).Methods Ninety-seven elderly T2DM patients admitted to Handan First Hospital from March 2021 to May 2024 were enrolled. According to the Mogensen diabetic nephropathy (DN) staging criteria, patients were divided into stage III group (n = 35), stage IV group (n = 20), stage V group (n = 11), and non-DN group (n = 31). Serum levels of β2-m, TFF3, and Lp-PLA2 were compared between patients with early renal impairment (stages III-V) and the non-DN group. Spearman correlation analysis was used to assess the relationships between serum β2-m, TFF3, Lp-PLA2 levels and early renal impairment. Patients were further divided into a progression group (n = 23, developed proteinuria progression) and a non-progression group (n = 74). Multivariate logistic regression was performed to identify factors influencing proteinuria progression. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of β2-m, TFF3, and Lp-PLA2.Results Serum β2-m, TFF3, and Lp-PLA2 levels in the stage V group were significantly higher than those in the stage III, stage IV, and non-DN groups (P < 0.05). Levels in the stage IV group were significantly higher than those in the stage III and non-DN groups (P < 0.05). Levels in the stage III group were significantly higher than those in the non-DN group (P < 0.05). Spearman analysis revealed positive correlations between serum β2-m, TFF3, Lp-PLA2 levels and early renal impairment (r = 0.512, 0.508, 0.594 respectively, P < 0.05). The progression group had a higher metformin usage rate, serum creatinine (Scr), β2-m, TFF3, and Lp-PLA2 levels compared to the non-progression group (P < 0.05). Multivariate logistic regression identified metformin use [O^R = 4.821 (95% CI: 2.119, 10.967) ], high β2-m [O^R = 5.217 (95% CI: 2.294, 11.869) ], high TFF3 [O^R = 4.112 (95% CI: 1.808, 9.355) ], and high Lp-PLA2 [O^R = 3.777 (95% CI: 1.660, 8.593) ] as independent risk factors for proteinuria progression (P < 0.05). ROC analysis showed that the sensitivities of β2-m, TFF3, Lp-PLA2, and their combination for predicting progression were 78.26% (95% CI: 0.725, 0.874), 82.61% (95% CI: 0.818, 0.935), 91.30% (95% CI: 0.856, 0.991), and 91.30% (95% CI: 0.851, 0.996), respectively; specificities were 85.14% (95% CI: 0.783, 0.961), 83.78% (95% CI: 0.764, 0.946), 72.97% (95% CI: 0.654, 0.816), and 93.24% (95% CI: 0.883, 0.998), respectively. The areas under the curve were 0.799 (95% CI: 0.682, 0.915), 0.843 (95% CI: 0.721, 0.967), 0.796 (95% CI: 0.679, 0.912), and 0.909 (95% CI: 0.778, 1.043), respectively, indicating higher predictive value for the combination.Conclusion Serum β2-m, TFF3, and Lp-PLA2 levels are positively correlated with early renal impairment in elderly T2DM patients. These biomarkers hold significant value in predicting proteinuria progression, with the combination demonstrating superior predictive efficacy.