Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands.
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Centraal Bureau voor de Statistiek, Heerlen, The Netherlands.
J Diabetes Complications. 2018 Mar;32(3):325-329. doi: 10.1016/j.jdiacomp.2017.12.011. Epub 2018 Jan 3.
Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes.
In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes, and additionally for other potential confounders and presence of vascular complication.
After full adjustment, levels of CML were positively associated with levels of MMP-2 and inversely with MMP-9. CEL was positively associated with MMP-3 and TIMP-1. MG-H1 was only associated with TIMP-1, whereas pentosidine was not associated with MMPs or TIMP-1.
We showed independent associations between several AGEs and markers of the MMP-TIMP system, which indicate specific AGE-MMP/TIMP-1 interactions potentially contributing to vascular complications in patients with type 1 diabetes.
晚期糖基化终产物（AGEs）和细胞外基质金属蛋白酶（MMPs）和基质金属蛋白酶抑制剂（TIMP）的改变重塑与 1 型糖尿病的血管并发症有关。实验研究表明，AGEs 调节 MMPs 和/或 TIMP-1 的产生。因此，我们研究了 1 型糖尿病个体中特定 AGEs 与 MMP-1、-2、-3、-9 和 -10 以及 TIMP-1 之间的相关性。
在 670 名 1 型糖尿病患者中，我们测定了血清蛋白结合 AGEs N-（羧甲基）赖氨酸（CML）、N-（羧乙基）赖氨酸（CEL）、5-羟-5-甲基咪唑酮（MG-H1）和戊糖的水平，以及 MMP-1、-2、-3、-9 和 -10 以及 TIMP-1。我们进行线性回归分析，以研究 AGEs 与 MMP-TIMP 系统标志物之间的相关性。分析调整了年龄、性别、HbA1c 和糖尿病病程，以及其他潜在的混杂因素和血管并发症的存在。
在充分调整后，CML 水平与 MMP-2 呈正相关，与 MMP-9 呈负相关。CEL 与 MMP-3 和 TIMP-1 呈正相关。MG-H1 仅与 TIMP-1 相关，而戊糖与 MMPs 或 TIMP-1 无关。
我们显示了几种 AGEs 与 MMP-TIMP 系统标志物之间的独立相关性，这表明特定的 AGE-MMP/TIMP-1 相互作用可能导致 1 型糖尿病患者的血管并发症。
