Introduction

This study aimed to investigate circulating biomarkers associated with the risk of developing diabetic peripheral neuropathy (DPN) and nephropathy in type 1 diabetes (T1D).

Materials and methods

Patients with childhood-onset T1D (n = 49, age 38.3 ± 3.8 yrs.) followed prospectively were evaluated after 30 years of diabetes duration. DPN was defined as an abnormality in nerve conduction tests. Matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1, neutrophil gelatinase-associated lipocalin-2 (NGAL), soluble P-selectin (sP-selectin), estimated GFR (eGFR), micro/macroalbuminuria and routine biochemistry were assessed. For comparison, control subjects were included (n = 30, age 37.9 ± 5.5 yrs.).

Results

In all, twenty-five patients (51 %) were diagnosed with DPN, and nine patients (18 %) had nephropathy (five microalbuminuria and four macroalbuminuria). Patients with DPN had higher levels of TIMP-1 (p = 0.036) and sP-selectin (p = 0.005) than controls. Patients with DPN also displayed higher levels of TIMP-1 compared to patients without DPN (p = 0.035). Patients with macroalbuminuria had kidney disease stage 3 with lower eGFR, higher levels of TIMP-1 (p = 0.038), and NGAL (p = 0.002). In all patients, we found only weak negative correlations between eGFR and TIMP-1 (rho = −0.304, p = 0.040) and NGAL (rho = −0.277, p = 0.062, ns), respectively. MMP-9 was higher in patients with microalbuminuria (p = 0.021) compared with normoalbuminuric patients.

Conclusions

Our findings indicate that TIMP-1 and MMP-9, as well as sP-selectin and NGAL, are involved in microvascular complications in T1D. Monitoring and targeting these biomarkers may be a potential strategy for treating diabetic nephropathy and neuropathy.

中文翻译：

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1 型糖尿病相关神经病和肾病微血管改变的全身生物标志物 - 一项前瞻性长期随访研究

介绍

本研究旨在调查与 1 型糖尿病 (T1D) 发生糖尿病周围神经病变 (DPN) 和肾病风险相关的循环生物标志物。

材料和方法

对儿童期发病的 T1D 患者（n  = 49，年龄 38.3 ± 3.8 岁）进行前瞻性随访，并在糖尿病病程 30 年后进行评估。DPN 被定义为神经传导测试异常。基质金属蛋白酶-9 (MMP-9) 及其组织抑制剂 TIMP-1、中性粒细胞明胶酶相关脂质运载蛋白-2 (NGAL)、可溶性 P-选择素 (sP-选择素)、估计 GFR (eGFR)、微量/大量白蛋白尿和常规生化进行了评估。为了进行比较，纳入了对照受试者（n  = 30，年龄 37.9 ± 5.5 岁）。

结果

总共有 25 名患者 (51%) 被诊断为 DPN，9 名患者 (18%) 患有肾病（5 名微量白蛋白尿和 4 名大量白蛋白尿）。DPN 患者的 TIMP-1 ( p  = 0.036) 和 sP-选择素 ( p  = 0.005)水平高于对照组。与无 DPN 的患者相比，DPN 患者的 TIMP-1 水平也较高 ( p  = 0.035)。大量白蛋白尿患者患有 3 期肾脏疾病，其 eGFR 较低，TIMP-1 ( p  = 0.038) 和 NGAL ( p  = 0.002) 水平较高。在所有患者中，我们发现 eGFR 与 TIMP-1（rho = -0.304， p  = 0.040）和 NGAL（rho = -0.277，p = 0.062，ns）之间仅存在微弱负相关 。 与白蛋白尿正常的患者相比，微量白蛋白尿患者的 MMP-9 较高 ( p = 0.021)。

结论

我们的研究结果表明 TIMP-1 和 MMP-9 以及 sP-选择素和 NGAL 与 T1D 的微血管并发症有关。监测和靶向这些生物标志物可能是治疗糖尿病肾病和神经病的潜在策略。