1型糖尿病患儿尿液中基质金属蛋白酶及金属蛋白酶组织抑制剂的水平

Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus.

作者信息

Yürük Yıldırım Zeynep, Yılmaz Alev, Pehlivanoğlu Cemile, Gedikbaşı Asuman, Yıldız Mehmet, Dirican Ahmet, Bundak Rüveyde, Darendeliler Feyza, Emre Sevinç, Nayır Ahmet

机构信息

İstanbul University İstanbul Faculty of Medicine, Department of Pediatric Nephrology, İstanbul, Turkey

Bakırköy Dr. Sadi Konuk Training and Research Hospital, Clinic of Biochemistry, İstanbul, Turkey

出版信息

J Clin Res Pediatr Endocrinol. 2019 May 28;11(2):157-163. doi: 10.4274/jcrpe.galenos.2018.2018.0221. Epub 2018 Nov 6.

Abstract

OBJECTIVE

Histopathological changes in the kidney in type 1 diabetes mellitus (T1DM) begin before detection of microalbuminuria. Therefore, there is interest in finding a better biomarker for the early detection of diabetic kidney injury. The aim of this present study was to determine whether urinary indicators of fibrosis are detectable early in the development of T1DM in children and if they may predict progressive renal injury.

METHODS

Urinary matrix metalloproteinase 2 and 9 (MMP2 and MMP9), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2) and transforming growth factor-β1 (TGF-β1) were assessed in 33 patients with T1DM with normal renal functions and in 24 healthy controls. Microalbuminuria was not present in the patient group with the exception of three patients. The results were adjusted to urine creatinine (Cr) and the differences between patients and controls were evaluated. These measurements were repeated after one year and the results were compared with the first year results.

RESULTS

Urine MMP2/Cr, MMP9/Cr, TIMP1/Cr, TIMP2/Cr, TGF-β1/Cr were not different between the patient and control groups (p>0.05). There were also no significant differences between the first and second year results for these biomarkers (p>0.05). None of these parameters were correlated with hemoglobin A1c, body mass index and duration of T1DM. Interestingly, all parameters were negatively correlated to age of onset of T1DM (p<0.05).

CONCLUSION

Our findings suggest that urinary biomarkers of fibrosis do not show an increase in diabetic children without microalbuminuria. The results also indicate that the risk of early fibrosis may increase as age of onset of T1DM decreases.

摘要

目的

1型糖尿病(T1DM)患者肾脏的组织病理学改变在微量白蛋白尿被检测出之前就已开始。因此,人们希望找到一种更好的生物标志物来早期检测糖尿病肾损伤。本研究的目的是确定在儿童T1DM发展早期是否可检测到纤维化的尿液指标,以及它们是否可以预测进行性肾损伤。

方法

对33例肾功能正常的T1DM患者和24例健康对照者的尿液基质金属蛋白酶2和9(MMP2和MMP9)、金属蛋白酶组织抑制剂1和2(TIMP1和TIMP2)以及转化生长因子-β1(TGF-β1)进行评估。除3例患者外,患者组均无微量白蛋白尿。将结果校正为尿肌酐(Cr),并评估患者与对照组之间的差异。一年后重复这些测量,并将结果与第一年的结果进行比较。

结果

患者组和对照组之间的尿MMP2/Cr、MMP9/Cr、TIMP1/Cr、TIMP2/Cr、TGF-β1/Cr无差异(p>0.05)。这些生物标志物在第一年和第二年的结果之间也无显著差异(p>0.05)。这些参数均与糖化血红蛋白、体重指数和T1DM病程无关。有趣的是,所有参数均与T1DM发病年龄呈负相关(p<0.05)。

结论

我们的研究结果表明,在无微量白蛋白尿的糖尿病儿童中,纤维化的尿液生物标志物没有增加。结果还表明,随着T1DM发病年龄的降低,早期纤维化的风险可能增加。

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