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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2024, Vol. 13 ›› Issue (03) : 145 -151. doi: 10.3877/cma.j.issn.2095-3216.2024.03.004

论著

2型糖尿病患者血清SMAD2和SOX6表达及其与蛋白尿的关系
陆文琪1,†(), 赵艳茹1, 李焕娣2, 樊欣娜1, 王佳1, 李萍1   
  1. 1. 066000　秦皇岛市第一医院营养科
    2. 066000　秦皇岛市第一医院肾内科
  • 收稿日期:2023-08-10 出版日期:2024-06-28
  • 通信作者: 陆文琪
  • 基金资助:
    秦皇岛市科学技术研究与发展计划(202101A216)

Serum expression of SMAD2 and SOX6 in patients with type 2 diabetes mellitus and their relationship with proteinuria

Wenqi Lu1,†(), Yanru Zhao1, Huandi Li2, Xinna Fan1, Jia Wang1, Ping Li1   

  1. 1. Department of Nutrition; Qinhuangdao First Hospital, Qinhuangdao 066000, Hebei Province, China
    2. Department of Nephrology; Qinhuangdao First Hospital, Qinhuangdao 066000, Hebei Province, China
  • Received:2023-08-10 Published:2024-06-28
  • Corresponding author: Wenqi Lu
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引用本文：

陆文琪, 赵艳茹, 李焕娣, 樊欣娜, 王佳, 李萍. 2型糖尿病患者血清SMAD2和SOX6表达及其与蛋白尿的关系[J]. 中华肾病研究电子杂志, 2024, 13(03): 145-151.

Wenqi Lu, Yanru Zhao, Huandi Li, Xinna Fan, Jia Wang, Ping Li. Serum expression of SMAD2 and SOX6 in patients with type 2 diabetes mellitus and their relationship with proteinuria[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(03): 145-151.

目的

探讨2型糖尿病患者(T2DM)血清SMAD2和SOX6表达及其与蛋白尿的关系。

方法

回顾性分析2022年3月至2023年4月我院收治的T2DM患者临床资料。根据尿白蛋白/肌酐比值(UACR)分为正常蛋白尿组(NA组，UACR <30 mg/g)、微量蛋白尿组(MA组，UACR 30～299 mg/g)和大量蛋白尿组(LA组，UACR≥300 mg/g)。收集患者一般资料和血清SMAD2、SOX6等实验室检测指标，Pearson方法分析T2DM患者血清SMAD2和SOX6水平与UACR、估算肾小球滤过率(eGFR)的相关性。受试者工作特征(ROC)曲线方法分析血清SMAD2、SOX诊断大量蛋白尿的作用。采用Logistic回归分析蛋白尿的影响因素。

结果

共纳入164例T2DM患者，其中NA组70例、MA组43例、LA组51例。NA组、MA组和LA组患者血清的SMAD2和SOX6水平逐次升高(F＝81.645、45.069，P均<0.001)。多因素Logistic回归分析显示高水平的SMAD2(OR＝2.015，95%CI：1.244～3.263)、SOX6(OR＝2.467，95%CI：1.476～4.122)、UACR(OR＝2.840，95%CI：1.605～5.023)和eGFR(OR＝0.799，95%CI：0.680～0.938)是蛋白尿的影响因素(P均<0.05)。相关性分析显示SMAD2、SOX6与UACR呈正相关(r＝0.559、0.628，P均<0.001)，与eGFR呈负相关(r＝－0.550、－0.474，P<0.001)。ROC曲线分析显示，血清SMAD2、SOX6诊断大量蛋白尿发生的曲线下面积(AUC)分别为0.844和0.765，截断值11.71 μg/L和3.67 ng/L。SMAD2和SOX6二者联合检测时AUC为0.912，优于SMAD2(Z/P＝2.995/0.002)或SOX6(Z/P＝3.861/<0.001)单独检测。

结论

T2DM患者血清的SMAD2和SOX6水平与蛋白尿具有一定相关性，其意义有待深入探讨。

关键词: 2型糖尿病, SMAD2, SOX6, 尿白蛋白/肌酐比值, 糖尿病肾脏病
Objective

To investigate the relationship of serum expression of SMAD2 and SOX6 with proteinuria in patients with type 2 diabetes mellitus (T2DM).

Methods

Clinical data of T2DM patients admitted to our hospital from March 2022 to April 2023 were analyzed retrospectively. According to urinary albumin/creatinine ratio (UACR), the patients were divided into three groups: normal albuminuria group (NA group, UACR <30 mg/g), microalbuminuria group (MA group, UACR 30-299 mg/g), and large albuminuria group (LA group, UACR≥300 mg/g). General information, serum expression of SMAD2 and SOX6, and other laboratory indicators were collected. Pearson correlation method was applied to analyze the correlation of serum SMAD2 and SOX6 levels with UACR and estimated glomerular filtration rate (eGFR) in the T2DM patients. The receiver operating characteristic (ROC) curve method was used to analyze the roles of serum SMAD2 and SOX in the diagnosis of macroproteinuria. The influencing factors of proteinuria were analyzed by logistic regression method.

Results

A total of 164 patients with T2DM were enrolled, including 70 in the NA group, 43 in the MA group, and 51 in the LA group. Serum levels of SMAD2 and SOX6 in the NA, MA and LA groups gradually increased (F=81.645, 45.069, all P<0.05). Multifactor logistic regression analysis showed that high levels of SMAD2 (OR=2.015, 95%CI: 1.244-3.263), SOX6 (OR=2.467, 95%CI: 1.476-4.122), UACR (OR=2.840, 95%CI: 1.605-5.023), and eGFR (OR=0.799, 95%CI: 0.680-0.938) were influencing factors of proteinuria (P<0.05). Correlation analysis showed that SMAD2 (r=0.559, P<0.001) and SOX6 (r=0.628, P<0.001) were positively correlated with UACR, while SMAD2 (r=-0.550, P<0.001) and SOX6 (r=-0.474, P<0.001) were negatively correlated with eGFR. ROC curve analysis showed that the areas under the curve (AUC) of serum SMAD2 and SOX6 for diagnosing large albuminuria were 0.844 and 0.765, and the cut-off values were 11.71 μg/L and 3.67 ng/L, respectivey. The AUC of combined SMAD2 and SOX6 for detection was 0.912, being better than that of SMAD2 (Z/P=2.995/0.002) or SOX6 (Z/P=3.861/<0.001) alone.

Conclusion

Serum levels of SMAD2 and SOX6 in T2DM patients were correlated with proteinuria, whose significance needs further study.

Key words: Type 2 diabetes mellitus, SMAD2, SOX6, Urinary albumin/creatinine ratio, Diabetic kidney disease
表1 一般资料及实验室检测指标比较
项目 NA组(70例) MA组(43例) LA组(51例) F/χ2值 P值
年龄(岁) 54.05±7.69 53.94±8.01 54.33±7.58 0.033 0.968
男/女 36/34 25/18 27/24 0.498 0.780
BMI(kg/m2) 24.46±1.94 24.73±2.52 24.29±2.16 0.483 0.618
吸烟 21 14 16 0.084 0.959
高血压 19 16 15 1.314 0.518
高血脂症 9 7 8 0.315 0.854
T2DM家族史 28 17 19 0.100 0.951
降糖治疗          
口服降糖药 22 13 16 0.656 0.957
胰岛素皮下注射 26 17 22    
联合用药 22 13 13    
T2DM病程(年) 5.92±1.40 8.89±2.35a 12.31±3.28ab 107.363 <0.001
SBP(mmHg) 121.79±8.95 130.14±9.5a 135.67±10.35ab 32.271 <0.001
DBP(mmHg) 77.64±7.06 79.26±8.34 77.72±7.91 0.679 0.509
DAO(U/L) 3.48±1.02 5.77±1.26a 7.09±1.53ab 127.041 <0.001
ET(EU/ml) 0.27±0.05 0.36±0.07a 0.41±0.05ab 97.967 <0.001
D-Lac(mmol/L) 4.61±0.56 5.72±0.67a 6.50±0.59ab 150.868 <0.001
FPG(mmol/L) 8.69±1.35 9.08±1.90 9.55±3.02 2.398 0.094
TC(mmol/L) 4.53±1.54 4.99±1.65 4.91±1.73 1.339 0.265
TG(mmol/L) 1.73±0.41 1.80±0.49 1.76±0.55 0.286 0.751
Scr(μmol/L) 83.07±14.63 85.49±11.08 185.62±17.20ab 841.947 <0.001
BUN(mmol/L) 5.69±1.42 6.34±1.15 35.27±6.31ab 1114.082 <0.001
HbA1c(%) 8.54±1.65 9.02±1.47 9.70±2.16a 6.243 0.002
FINS(mU/L) 10.53±1.77 11.46±2.15 12.19±2.55a 9.083 <0.001
HOMA-IR 3.47±1.24 4.19±1.38a 4.55±1.49a 9.928 <0.001
UACR(mg/g) 16.09±3.50 98.76±17.49a 367.18±39.40ab 3325.513 <0.001
eGFR[ml/(min·1.73 m2] 94.36±14.14 80.58±13.07 69.47±6.52ab 64.904 <0.001
表2 血清SMAD2和SOX6水平比较
指标 NA组(70例) MA组(43例) LA组(51例) F值 P值
SMAD2(μg/L) 9.13±1.57 11.05±1.82a 13.79±2.54ab 81.645 <0.001
SOX6(ng/L) 2.69±0.55 3.12±0.75a 3.88±0.78ab 45.069 <0.001
表3 影响蛋白尿的单因素Logistic回归分析
项目 B值 标准误 Wald P值 OR值 95%CI
T2DM病程 0.400 0.217 3.411 0.065 1.493 0.975～2.284
SBP 0.420 0.274 2.349 0.125 1.522 0.889～2.604
DAO 0.017 0.255 0.005 0.944 1.018 0.617～1.678
ET 0.614 0.341 3.248 0.071 1.849 0.947～3.607
D-Lac 0.265 0.179 2.198 0.138 1.304 0.918～1.852
HbA1c 0.063 0.162 0.155 0.693 1.066 0.775～1.464
BUN 0.712 0.365 3.810 0.051 2.039 0.997～4.169
Scr 1.084 0.284 14.572 <0.001 2.957 1.694～5.159
FINS 0.825 0.426 3.755 0.053 2.283 0.991～5.261
HOMA-IR 0.894 0.458 3.814 0.051 2.446 0.996～6.002
UACR 1.168 0.342 11.561 0.001 3.199 1.636～6.253
eGFR －0.207 0.076 7.421 0.006 0.813 0.700～0.943
SMAD2 1.059 0.291 13.248 <0.001 2.884 1.630～5.101
SOX6 0.941 0.275 11.705 0.001 2.562 1.494～4.392
表4 影响蛋白尿的多因素Logistic回归分析
项目 B值 标准误 Wald P值 OR值 95%CI
Scr 0.464 0.277 2.817 0.093 1.592 0.925～2.738
UACR 1.043 0.291 12.866 <0.001 2.840 1.605～5.023
eGFR －0.224 0.082 7.488 0.006 0.799 0.680～0.938
SMAD2 0.700 0.246 8.111 0.004 2.015 1.244～3.263
SOX6 0.903 0.262 11.878 0.001 2.467 1.476～4.122
图1 T2DM患者SMAD2水平与UACR和eGFR的相关性分析
图2 2型糖尿病患者SOX6水平与UACR和eGFR的相关性分析
图3 血清SMAD2、SOX6诊断大量蛋白尿发生的ROC曲线
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