Relationships between three islet autoantibodiesand renal damage in children with type 1 diabetes mellitus
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摘要:目的 探讨血清锌转运体8自身抗体（ZnT8A）、谷氨酸脱羧酶抗体（GADA）及蛋白酪氨酸磷酸酶抗体（IA-2A）水平与1型糖尿病患儿并发肾损害的关系。方法 选取123例1型糖尿病患儿纳入研究组，另选取同期体检的105例健康儿童纳入对照组，检测并比较2组血清ZnT8A、GADA及IA-2A水平。评估研究组患儿肾功能状态，根据肾损害并发情况将患儿分为并发组与未并发组，比较2组患儿血清ZnT8A、GADA、IA-2A阳性率，并采用Logistic多元回归分析法分析血清ZnT8A、GADA、IA-2A以及其他因素与1型糖尿病患儿并发肾损害的关系。结果 研究组血清ZnT8A、GADA、IA-2A阳性率（41.46%、60.98%、45.53%）均高于对照组，差异有统计学意义（P < 0.05）；研究组肾损害并发率为38.21%（47/123），并发组血清ZnT8A、GADA、IA-2A阳性率（74.47%、85.11%、78.72%）均高于未并发组，差异有统计学意义（P < 0.05）；多因素Logistic回归分析显示，1型糖尿病病程、胱抑素C（CysC）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、舒张压、血尿酸、血红蛋白（Hb）以及血清ZnT8A、GADA、IA-2A均是1型糖尿病患儿并发肾损害的影响因素（P < 0.05）。结论 1型糖尿病患儿血清ZnT8A、GADA、IA-2A阳性率高于健康儿童，且并发肾损害患儿的阳性率较未并发患儿高。血清ZnT8A、GADA、IA-2A阳性和糖尿病病程偏长、高CysC、高FBG、高HbA1c、高NAG、高血尿酸、高舒张压、低Hb均可增加1型糖尿病患儿并发肾损害的风险，临床医生需据此加强防控。
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关键词:
- 锌转运体8自身抗体 /
- 谷氨酸脱羧酶抗体 /
- 蛋白酪氨酸磷酸酶抗体 /
- 1型糖尿病 /
- 肾损害
Abstract:Objective To explore the relationships between serum zinc transporter 8 autoantibody (ZnT8A), glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A) and renal damage in children with type 1 diabetes mellitus.Methods A total of 123 children with type 1 diabetes mellitus (study group) and 105 healthy children (control group) at same period were selected as study subjects, and the levels of serum ZnT8A, GADA and IA-2A were detected and compared between the two groups. The renal function of the children in the study group was evaluated, and the children were divided into complicated group and the non-complicated group according to the concurrent conditions of renal damage, and the positive rates of serum ZnT8A, GADA and IA-2A were compared between the complicated group and the non-complicated group. The relationships between the positive of serum ZnT8A, GADA, IA-2A and renal damage in children with type 1 diabetes mellitus were analyzed by Logistic multiple regression analysis.Results The positive rates of ZnT8A, GADA and IA-2A in the study group were 41.46%, 60.98% and 45.53%, respectively, and were significantly higher than those in the control group (P < 0.05). The complication rate of renal damage in the study group was 38.21% (47/123), and the positive rates of serum ZnT8A, GADA and IA-2A in the complicated group were 74.47%, 85.11% and 78.72%, respectively, which were higher than those in non-complicated group (P < 0.05). Multivariate Logistic regression analysis showed that the course of type 1 diabetes, cystatin C (CysC), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), urinary N-acetyl-β-d-glucosaminidase (NAG), diastolic blood pressure, serum uric acid, hemoglobin (Hb) and serum ZnT8A, GADA and IA-2A were all risk factors for renal damage in children with type 1 diabetes (P < 0.05).Conclusion The positive rates of serum ZnT8A, GADA and IA-2A in children with type 1 diabetes mellitus are significantly higher than those in normal children, and positive rates of children with renal damage complicating renal injury are higher than those in children without renal damage. The positive results of serum levels of ZnT8A, GADA and IA-2A, longer course of diabetes, higher CysC, higher FBG, higher HbA1c, higher NAG, higher serum uric acid, higher diastolic blood pressure and lower Hb can also increase the risk of renal damage in children with type 1 diabetes, so prevention and control should be strengthened accordingly. -
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表 1 研究组与对照组血清ZnT8A、GADA、IA-2A阳性情况比较[n(%)]
组别 n ZnT8A阳性 GADA阳性 IA-2A阳性 对照组 105 2(1.90) 5(4.76) 3(2.86) 研究组 123 51(41.46) * 75(60.98) * 56(45.53) * ZnT8A: 锌转运体8自身抗体; GADA: 谷氨酸脱羧酶抗体;
IA-2A: 蛋白酪氨酸磷酸酶抗体。
与对照组比较, *P <0.05。
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表 2 并发组与未并发组血清ZnT8A、GADA、IA-2A阳性情况比较[n(%)]
组别 n ZnT8A阳性 GADA阳性 IA-2A阳性 并发组 47 33(70.21) 39(82.98) 35(74.47) 未并发组 76 18(23.68) 36(47.37) 21(27.63) 与对照组比较, *P <0.05。
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表 3 并发组与未并发组指标比较(x±s)[n(%)]
指标 并发组(n=47) 未并发组(n=76) t/ χ 2 P 1型糖尿病病程/年 2.95±0.34 1.98±0.39 14.060 < 0.001 CysC/(mg/L) 1.46±0.21 1.04±0.20 11.103 < 0.001 FBG/(mmol/L) 11.65±1.32 9.59±1.68 7.148 < 0.001 HbA1c/% 10.89±1.56 8.42±1.83 7.684 < 0.001 NAG/(U/mmol·Cr) 33.25±5.17 21.32±3.86 14.598 < 0.001 TC/(mmol/L) 4.59±0.91 4.28±0.84 1.926 0.056 舒张压/mmHg 82.61±12.04 76.59±9.47 3.083 0.003 收缩压/mmHg 126.95±21.06 122.84±18.65 1.130 0.261 血尿酸/(μmol/L) 304.11±57.58 265.37±48.29 4.013 < 0.001 Hb/(g/L) 115.33±18.54 132.14±24.11 4.088 < 0.001 TG/(mmol/L) 1.08±0.19 1.03±0.16 1.566 0.120 ALB/(g/L) 37.13±6.24 39.46±7.35 1.807 0.073 ZnT8A阳性 33(70.21) 18(23.68) 25.903 < 0.001 GADA阳性 39(82.98) 36(47.37) 15.476 < 0.001 IA-2A阳性 35(74.47) 21(27.63) 25.688 < 0.001 CysC: 胱抑素C; FBG: 空腹血糖; HbA1c: 糖化血红蛋白; NAG: 尿N-乙酰-β-D-氨基葡萄糖苷酶; TC: 总胆固醇; Hb: 血红蛋白;
TG: 三酰甘油; ALB: 白蛋白; ZnT8A: 锌转运体8自身抗体; GADA: 谷氨酸脱羧酶抗体; IA-2A: 蛋白酪氨酸磷酸酶抗体。
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表 4 1型糖尿病患儿并发肾损害的影响因素Logistic多元回归分析
因素 β SE Wald χ2 P OR 95%CI 1型糖尿病病程 1.365 0.384 12.636 < 0.001 3.916 3.720~4.112 CysC 1.209 0.376 10.339 < 0.001 3.350 3.183~3.518 FBG 0.971 0.363 7.155 0.028 2.641 2.509~2.773 HbA1c 1.012 0.366 7.645 0.023 2.751 2.613~2.889 NAG 1.371 0.385 12.681 < 0.001 3.939 3.742~4.136 舒张压 0.932 0.367 6.449 0.036 2.540 2.413~2.667 血尿酸 0.958 0.362 7.003 0.030 2.606 2.476~2.736 Hb -0.526 0.197 7.129 0.029 0.591 0.561~0.621 ZnT8A阳性 1.679 0.394 18.159 < 0.001 5.360 5.092~5.628 GADA阳性 1.405 0.386 13.249 < 0.001 4.076 3.872~4.280 IA-2A阳性 1.653 0.392 17.782 < 0.001 5.223 4.962~5.484 CysC: 胱抑素C; FBG: 空腹血糖; HbA1c: 糖化血红蛋白; NAG: 尿N-乙酰-β-D-氨基葡萄糖苷酶; Hb: 血红蛋白;
ZnT8A: 锌转运体8自身抗体; GADA: 谷氨酸脱羧酶抗体; IA-2A: 蛋白酪氨酸磷酸酶抗体。
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