Correlation between Blood UA，Smad1 Protein，Urine mALB Levels and the Therapeutic Effect of Dapagliflozin in Patients with Type 2 Diabetes Nephropathy
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摘要:
目的 观察2型糖尿病肾病患者血尿酸（uric acid，UA）、Smad同源物1（recombinant mothers against decapentaplegic homolog 1，Smad1）蛋白、尿微量白蛋白（urine microalbumin，mALB）含量，并分析三者与达格列净治疗2型糖尿病肾病效果的相关性。 方法 选取2021年6月至2022年9月皖南医学院第二附属医院2型糖尿病肾病患者纳入糖尿病肾病组（n = 170），另取同期单纯2型糖尿病患者纳入单纯糖尿病组（n = 120），所有患者入院时均接受血UA、Smad1蛋白、尿mALB检测，对比糖尿病肾病组与单纯糖尿病组上述3项指标水平。所有2型糖尿病肾病患者均采用达格列净治疗，随访3个月，观察患者治疗效果。依据治疗效果分为有效组（n = 142）与无效组（n = 28），对比有效组与无效组血UA、Smad1蛋白、尿mALB含量，分析3项指标与达格列净治疗2型糖尿病肾病效果的相关性，绘制受试者工作特征曲线（ROC）分析上述3项指标对达格列净治疗2型糖尿病肾病效果的预测价值。 结果 糖尿病肾病组血UA、Smad1蛋白、尿mALB水平高于单纯糖尿病组（t = 8.843、12.097、8.858，P < 0.05）；治疗3个月后，170例2型糖尿病肾病患者中有效142例（83.53%），无效28例（16.47%）；无效组血UA、Smad1蛋白、尿mALB水平高于有效组（t = 3.508、4.622、3.563，P < 0.05）；经点二列相关性分析结果显示，血UA、Smad1蛋白、尿mALB水平与达格列净治疗2型糖尿病肾病效果呈负相关（r = -0.261、-0.336、-0.265，P < 0.05）；经Logistic回归分析，结果显示，血UA（95%CI：1.001～1.021）、Smad1蛋白（95%CI：1.167～1.610）、尿mALB（95%CI：1.011～1.048）水平升高是达格列净治疗2型糖尿病肾病无效的危险因素（OR=1.011、1.371、1.029，P < 0.05）；绘制受试者工作特征曲线（receiver operator characteristic curve，ROC），结果显示，血UA（95%CI：0.622～0.793）、Smad1蛋白（95%CI：0.685～0.841）、尿mALB（95%CI：0.630～0.803）水平对达格列净治疗2型糖尿病肾病效果具有一定预测价值（AUC=0.707、0.763、0.716），联合检测（95%CI：0.734～0.881）预测价值更高（AUC=0.808）。 结论 血UA、Smad1蛋白、尿mALB水平与达格列净治疗2型糖尿病肾病效果密切相关，可用于预测其治疗效果。 -
关键词:
- 2型糖尿病肾病 /
- 血尿酸 /
- Smad同源物1蛋白 /
- 达格列净
Abstract:Objective To observe the levels of uric acid, Smad1 protein, and urine microalbumin in patients with type 2 diabetic nephropathy, and to analyze the correlation between these three factors and the effectiveness of dapagliflozin in treating type 2 diabetic nephropathy. Methods From June 2021 to September 2022, 170 patients with type 2 diabetic nephropathy in our hospital were included in the diabetic nephropathy group. Another 120 patients with only type 2 diabetes during the same period were included in the simple diabetes group. All patients underwent blood UA, Smad1 protein, and urine mALB tests upon admission, and the levels of these three indicators were compared between the diabetic nephropathy group and the simple diabetes group. All type 2 diabetic nephropathy patients were treated with dapagliflozin and followed up for three months to observe the treatment effect. Based on the treatment effect, they were divided into the effective group （n = 142） and the ineffective group （n = 28）. The blood UA, Smad1 protein and urine mALB contents of the effective group and ineffective group were compared, and the correlation between the three indexes and the therapeutic effect of Dapagliflozin on type 2 diabetic nephropathy was analyzed. A receiver operating characteristic curve （ROC） was plotted to analyze the predictive value of the above three indicators for the effect of dapagliflozin treatment for type 2 diabetic nephropathy. Results Diabetic nephropathy group had higher levels of blood UA, Smad1 protein, and urine mALB compared to the simple diabetic group （t = 8.843, 12.097, 8.858, P < 0.05）. After 3 months of treatment, out of 170 type 2 diabetic nephropathy patients, 142 cases were effectively treated （83.53%）, while 28 cases were not （16.47%）. The ineffective group had higher levels of blood UA, Smad1 protein, and urine mALB compared to the effective group （t = 3.508, 4.622, 3.563, P < 0.05）. Correlation analysis showed that blood UA, Smad1 protein, and urine mALB levels were negatively correlated with the efficacy of Dapagliflozin treatment for type 2 diabetic nephropathy （r = -0.261, -0.336, -0.265, P < 0.05）. Logistic regression analysis indicated that elevated levels of blood UA （95%CI: 1.001～1.021）, Smad1 protein （95%CI: 1.167～1.610）, and urine mALB （95%CI: 1.011～1.048） were risk factors for the ineffectiveness of Dapagliflozin treatment for type 2 diabetic nephropathy （OR=1.011, 1.371, 1.029, P < 0.05）. The receiver operator characteristic curve （ROC） analysis showed that blood UA （95%CI: 0.622～0.793）, Smad1 protein （95%CI: 0.685～0.841）, and urine mALB （95%CI: 0.630～0.803） levels had some predictive value for the efficacy of Dapagliflozin treatment for type 2 diabetic nephropathy （AUC = 0.707, 0.763, 0.716）, with higher predictive value when combined （95%CI: 0.734～0.881, AUC = 0.808）. Conclusion The levels of serum UA, Smad1 protein and urine mALB are closely related to the therapeutic effect of Dapagliflozin on type 2 diabetic nephropathy, which can be used to predict its therapeutic effect. -
Key words:
- Type 2 diabetic nephropathy /
- Blood uric acid /
- Smad homologue 1 protein /
- Dapagliflozin
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图 1 血UA、Smad1蛋白、尿mALB水平预测达格列净治疗2型糖尿病肾病效果的ROC图
Figure 1. ROC diagram of predicting the effect of Dapagliflozin on type 2 diabetic nephropathy by blood UA，Smad1 protein and urine mALB levels
表 1 糖尿病肾病组与单纯糖尿病组一般资料比较[（$\bar x \pm s $）/n（%）]
Table 1. Comparison of general data between diabetic nephropathy group and simple diabetes group [（$\bar x \pm s $）/n（%）]
指标 糖尿病肾病组（n=170） 单纯糖尿病组（n=120） χ2/t P 性别 男 104（61.18） 71（59.17） 0.119 0.730 女 66（38.82） 49（40.83） 年龄（岁） 59.04±6.37 58.79±6.82 0.320 0.750 体重指数（kg/m2） 26.93±2.36 27.06±2.43 0.456 0.649 糖尿病病程（a） 10.42±3.58 10.21±3.76 0.482 0.630 吸烟史 39（22.94） 31（25.83） 0.321 0.571 饮酒史 34（20.00） 28（23.33） 0.465 0.495 高血压 122（71.76） 78（65.00） 1.504 0.220 
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表 2 糖尿病肾病组与单纯糖尿病组血UA、Smad1蛋白、尿mALB水平比较（$\bar x \pm s $）
Table 2. Comparison of serum UA，Smad1 protein and urinary mALB levels between diabetic nephropathy group and simple diabetic group（$ \bar x \pm s$）
组别 血UA（μmol/L） Smad1蛋白（ng/L） 尿mALB（mg/L） 糖尿病肾病组（n=170） 392.58±69.78 13.28±4.29 118.93±34.74 单纯糖尿病组（n=120） 323.66±58.54 8.02±2.46 86.32±24.36 t 8.843 12.097 8.858 P <0.001* <0.001* <0.001* *P < 0.05。
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表 3 有效组与无效组基线资料及血UA、Smad1蛋白、尿mALB水平比较[（$\bar x \pm s $）/n（%）]
Table 3. Comparison of baseline data，blood UA，Smad1 protein and urinary mALB levels between the effective and ineffective groups [（$\bar x \pm s $）/n（%）]
指标 有效组（n=142） 无效组（n=28） χ2/t P 性别 男 85（59.86） 19（67.86） 0.630 0.427 女 57（40.14） 9（32.14） 年龄（岁） 58.93±6.51 59.68±3.29 0.594 0.553 体重指数（kg/m2） 26.89±2.32 27.16±2.03 0.574 0.567 糖尿病病程（a） 10.21±3.46 10.95±3.12 1.050 0.295 平均动脉压（mmHg） 113.08±11.86 109.72±9.53 1.411 0.160 空腹血糖（mmol/L） 7.25±0.92 7.34±1.07 0.460 0.646 eGFR 55.39±7.23 53.76±6.67 1.104 0.271 2型糖尿病肾病分期 Ⅰ-Ⅱ期 97（68.31） 17（60.71） 0.611 0.435 Ⅲ-Ⅳ期 45（31.69） 11（39.29） 血UA（μmol/L） 385.52±62.43 428.37±36.92 3.508 0.001* Smad1蛋白（ng/L） 12.74±3.61 16.02±2.29 4.622 <0.001* 尿mALB（mg/L） 115.48±29.57 136.41±21.35 3.563 0.001* *P < 0.05。
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表 4 血UA、Smad1蛋白、尿mALB水平与达格列净治疗2型糖尿病肾病效果的相关性
Table 4. Correlation between serum UA，Smad1 protein and urinary mALB levels and the effect of dagaglipzin on type 2 diabetic nephropathy
指标 r P 血UA −0.261 0.001* Smad1蛋白 −0.336 <0.001* 尿mALB −0.265 <0.001* *P < 0.05。
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表 5 血UA、Smad1蛋白、尿mALB水平对达格列净治疗2型糖尿病肾病效果的影响
Table 5. Effects of serum UA，Smad1 protein and urinary mALB levels on the efficacy of daglipzin in the treatment of type 2 diabetic nephropathy
自变量 β 标准误 Waldχ2 P OR 95%CI 血UA 0.011 0.005 5.101 0.024* 1.011 1.001～1.021 Smad1蛋白 0.315 0.082 14.733 <0.001* 1.371 1.167～1.610 尿mALB 0.029 0.009 10.003 0.002* 1.029 1.011～1.048 *P < 0.05。
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表 6 血UA、Smad1蛋白、尿mALB水平对达格列净治疗2型糖尿病肾病效果的预测价值
Table 6. The predictive value of serum UA，Smad1 protein and urinary mALB levels in the treatment of type 2 diabetic nephropathy with daglipzin
检验变量 AUC 标准误 P 95%CI cut-off 敏感度 特异度 约登指数 血UA 0.707 0.043 0.001* 0.622～0.793 404.040 0.786 0.542 0.328 Smad1蛋白 0.763 0.040 <0.001* 0.685～0.841 14.025 0.821 0.592 0.413 尿mALB 0.716 0.044 <0.001* 0.630～0.803 121.695 0.786 0.563 0.349 联合 0.808 0.038 <0.001* 0.734～0.881 - 0.893 0.542 0.435 *P < 0.05。
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