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1型糖尿病患儿细胞外(血清)基质金属蛋白酶水平及其与糖尿病酮症酸中毒和脑水肿的关系

Extracellular(Serum) Levels of Matrix Metalloproteinases in Pediatric Type 1 Diabetes Mellitus and Association with Diabetic Ketoacidosis and Cerebral Edema.

作者信息

Xu Qingbo, Yang Yu, Huang Qiang, Xie Liling, Feng Yaqin, Yang Li

机构信息

Department of Endocrinology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, 330038, People's Republic of China.

The Affiliated Children's Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330038, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2025 Mar 20;18:819-830. doi: 10.2147/DMSO.S507337. eCollection 2025.

DOI:10.2147/DMSO.S507337
PMID:40129484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11932032/
Abstract

BACKGROUND

Type 1 diabetes mellitus (T1DM) in children is associated with acute complications such as diabetic ketoacidosis (DKA) and the severe risk of diabetic ketoacidosis-related cerebral edema (DKACE). Matrix metalloproteinases (MMPs) are implicated in inflammation and tissue remodeling, potentially contributing to these complications. This study explores the role of MMPs as biomarkers in pediatric T1DM patients with DKA and DKACE.

METHODS

We conducted a systematic cross-sectional study at Jiangxi Children's Hospital, enrolling 56 pediatric patients with T1DM, categorized into three groups: T1DM without complications, DKA, and DKACE. Serum levels of MMP-2, MMP-3, and MMP-9 were measured through ELISA. Statistical analyses assessed correlations between MMPs, glucose metabolism, and inflammatory markers, evaluating potential biomarker utility in disease characterization.

RESULTS

MMP-3 and MMP-9 levels were significantly elevated in the DKACE group compared to the T1DM and DKA groups, exhibiting strong correlations with decreased pH and bicarbonate levels (both p < 0.001). MMP-2 levels were reduced in DKACE, correlating positively with pH and bicarbonate levels. Post-clinical improvement analyses demonstrated no significant differences in MMP levels between DKA and DKACE groups, suggesting stabilization post-treatment regardless of initial acidosis severity.

CONCLUSION

The distinct patterns of MMP-3 and MMP-9 elevations in DKACE highlight their potential as biomarkers for identifying and monitoring severe DKA complications. The findings suggest these enzymes play a significant role in cerebral edema pathophysiology, making them viable targets for future therapeutic interventions.

摘要

背景

儿童1型糖尿病(T1DM)与急性并发症如糖尿病酮症酸中毒(DKA)以及糖尿病酮症酸中毒相关脑水肿(DKACE)的严重风险相关。基质金属蛋白酶(MMPs)参与炎症和组织重塑,可能导致这些并发症。本研究探讨MMPs作为生物标志物在患有DKA和DKACE的儿科T1DM患者中的作用。

方法

我们在江西省儿童医院进行了一项系统性横断面研究,纳入56例儿科T1DM患者,分为三组:无并发症的T1DM、DKA和DKACE。通过酶联免疫吸附测定法(ELISA)测量血清中MMP-2、MMP-3和MMP-9的水平。统计分析评估了MMPs、葡萄糖代谢和炎症标志物之间的相关性,评估了在疾病特征描述中潜在的生物标志物效用。

结果

与T1DM组和DKA组相比,DKACE组的MMP-3和MMP-9水平显著升高,与pH值降低和碳酸氢盐水平降低呈强相关(均p < 0.001)。DKACE组的MMP-2水平降低,与pH值和碳酸氢盐水平呈正相关。临床改善后分析表明,DKA组和DKACE组之间的MMP水平无显著差异,表明无论初始酸中毒严重程度如何,治疗后均趋于稳定。

结论

DKACE中MMP-3和MMP-9升高的独特模式突出了它们作为识别和监测严重DKA并发症生物标志物的潜力。研究结果表明这些酶在脑水肿病理生理学中起重要作用,使其成为未来治疗干预的可行靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/15c5a0fa057d/DMSO-18-819-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/d68c584468ff/DMSO-18-819-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/0b1d2e120466/DMSO-18-819-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/15c5a0fa057d/DMSO-18-819-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/d68c584468ff/DMSO-18-819-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/0b1d2e120466/DMSO-18-819-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99ea/11932032/15c5a0fa057d/DMSO-18-819-g0003.jpg

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