Abstract:

Objective　To explore the clinical value of serum lipid coated protein 2 (Perilipin-2) and urine axon-guiding factor 4 (Netrin-4) in the prediction of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods　This was a cross-sectional study. A total of 208 patients with T2DM treated at Xi'an Daxing Hospital from July 2020 to July 2023 were selected as the study objects. According to their urinary albumin excretion rates (UAER), the patients were divided into a simple T2DM group (UAER<30 mg/24 h) and a DN group (30 mg/24 h≤UAER<300 mg/24 h). There were 74 males and 56 females in the simple T2DM group; they were (56.18±7.38) years old; their body mass index was (22.73 ± 4.37) kg/m². There were 42 males and 36 females in the DN group; they were (57.02±7.13) years old; their body mass index was (23.68±4.29) kg/m². A total of 120 healthy examinees during the same period were selected as a healthy control group. Serum Perilipin-2 and urine Netrin-4 were detected in all the subjects. The contents of serum Perilipin-2 and urine Netrin-4 in all the subjects were detected. t and χ² tests were used for the statistical analysis. The receiver operating characteristic curve (ROC) was used to evaluate the clinical value of serum Perilipin-2 combined with urinary Netrin-4 in the prediction of DN in the patients. Multivariate logistic regression analysis was used to explore the related factors of DN. Results　The serum levels of Perilipin-2 in the simple T2DM group [(12.52±3.37) μg/L] and the DN group [(20.84±3.42) μg/L] were higher than that in the healthy control group [(5.13±2.15) μg/L], and the level in the DN group was higher than that in the simple T2DM group, with a statistical difference between the 3 groups (F=15.14; P<0.05). The urinary Netrin-4 levels in the simple T2DM group [(63.93±8.72) μg/L] and the DN group [(41.32±7.04) μg/L] were lower than that in the healthy control group [(98.64±15.37) μg/L], and the level in the DN group was lower than that in the simple T2DM group, with a statistical difference between the 3 groups (F=37.03; P<0.05). The areas under the curves (AUC) of serum Perilipin-2 and urine Netrin-4 for the occurrence of DN in the patients were 0.739 (95%CI 0.694-0.789) and 0.835 (95%CI 0.791-0.884), respectively; and the AUC of their combination was 0.903 (95%CI 0.858-0.954). The number of the patients with grade 2 or above hypertension in the DN group was higher than that in the simple T2DM group (χ²=11.68; P<0.05). The multivariate logistic regression analysis showed that a history of grade II or above hypertension (OR=3.232, 95%CI 1.499-6.968), serum Perilipin-2 (OR=4.252, 95%CI 1.752-10.267), and urinary Netrin-4 (OR=5.145, 95%CI 1.985-13.337) were the influential factors for the occurrence of DN in the patients (all P<0.05). Conclusion　Serum Perilipin-2 and urine Netrin-4 can be used as biomarkers for predicting the occurrence of DN in patients with T2DM, and their combination can improve the clinical diagnostic value.

Key words:

Type 2 diabetes mellitus, Diabetic nephropathy, Lipid droplets coated with protein 2, Urine axon-directing factor 4, Clinical value

摘要：

目的　探讨血清脂滴包被蛋白2（Perilipin-2）联合尿液轴突导向因子4（Netrin-4）预测2型糖尿病（T2DM）患者糖尿病肾病（DN）的临床价值。方法　采用横断面研究，选取2020年7月至2023年7月期间西安大兴医院收治的208例T2DM病患者作为研究对象，依据尿白蛋白排泄率（UAER）将患者分为单纯T2DM组和DN组。单纯T2DM组（UAER<30 mg/24 h）：男74例、女56例，年龄（56.18±7.38）岁，体重指数（22.73±4.37）kg/m²。DN组（30 mg/24 h≤UAER<300 mg/24 h）：男42例、女36例，年龄（57.02±7.13）岁，体重指数（23.68±4.29）kg/m²。选取同期入院健康体检者120名作为健康对照组。检测所有研究对象血清Perilipin-2，尿Netrin-4含量。采用t检验、χ²检验进行统计分析，受试者操作特征曲线（ROC）评估血清Perilipin-2联合尿Netrin-4预测T2DM患者DN的临床价值，多因素logistic回归分析探讨DN的相关因素。结果　单纯T2DM组、DN组血清Perilipin-2水平分别为（12.52±3.37） μg/L、（20.84±3.42） μg/L，均高于健康对照组［（5.13±2.15） μg/L］，且DN组高于单纯T2DM组，3组比较，差异有统计学意义（F=15.14，P<0.05）。单纯T2DM组、DN组尿Netrin-4水平分别为（63.93±8.72） μg/L、（41.32±7.04） μg/L，均低于健康对照组［（98.64±15.37） μg/L］，且DN组低于单纯T2DM组，3组比较，差异有统计学意义（F=37.03，P<0.05）。血清Perilipin-2、尿Netrin-4对T2DM患者发生DN的曲线下面积（AUC）分别为0.739［95%置信区间（CI） 0.694～0.789］、0.835（95%CI 0.791～0.884），两者联合预测的AUC为0.903（95%CI 0.858～0.954）。DN组二级及以上高血压史人数高于单纯T2DM组（χ²=11.68，P<0.05）；多因素logistic逐步回归分析显示，二级及以上高血压史（OR=3.232，95%CI 1.499～6.968）、血清Perilipin-2（OR=4.252，95%CI 1.752～10.267）、尿Netrin-4（OR=5.145，95%CI 1.985～13.337）均是T2DM患者发生DN的影响因素（均P<0.05）。结论　血清Perilipin-2、尿Netrin-4可作为预测T2DM患者DN发生的生物标志物，且二者联合检测能提高临床诊断价值。

关键词:

2型糖尿病, 糖尿病肾病, 脂滴包被蛋白2, 尿液轴突导向因子4, 临床价值