晚期糖基化终产物甲基乙二醛衍生的氢化咪唑酮-1与儿童糖尿病患者动脉粥样硬化的早期迹象

The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes.

作者信息

Heier Martin, Margeirsdottir Hanna Dis, Torjesen Peter Abusdal, Seljeflot Ingebjørg, Stensæth Knut Haakon, Gaarder Mario, Brunborg Cathrine, Hanssen Kristian Folkvord, Dahl-Jørgensen Knut

机构信息

Department of Pediatrics, Oslo University Hospital, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway

Faculty of Medicine, University of Oslo, Oslo, Norway Oslo Diabetes Research Centre, Oslo, Norway Akershus University Hospital, Lørenskog, Norway.

出版信息

Diab Vasc Dis Res. 2015 Mar;12(2):139-45. doi: 10.1177/1479164114560910. Epub 2015 Jan 23.

DOI:10.1177/1479164114560910

PMID:25616705

Abstract

BACKGROUND

Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma.

AIM

To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls.

METHODS

A total of 314 diabetes patients aged 8-18 years were compared with 120 healthy controls. Serum methylglyoxal-derived hydroimidazolone-1 was measured by immunoassay. Atherosclerosis was evaluated by assessing carotid intima-media thickness by ultrasound, arterial stiffness by Young's modulus and inflammation by C-reactive protein.

RESULTS

Methylglyoxal-derived hydroimidazolone-1 was significantly increased in the diabetes group compared with controls, 155.3 (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, p = 0.003, as was C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, p < 0.001. There was no significant difference between the groups regarding carotid intima-media thickness or Young's modulus. Multiple regression analysis showed a significant positive association between methylglyoxal-derived hydroimidazolone-1 and C-reactive protein in the diabetes group.

CONCLUSION

Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes.

摘要

背景

晚期蛋白质糖基化是包括动脉粥样硬化在内的晚期糖尿病并发症发生发展的重要机制。甲基乙二醛衍生的1-氢咪唑啉酮是人体血浆中最丰富的晚期糖基化终产物。

目的

研究1型糖尿病儿童和青少年及健康对照者中甲基乙二醛衍生的1-氢咪唑啉酮与动脉粥样硬化早期征象之间的关系。

方法

将314例8-18岁的糖尿病患者与120例健康对照者进行比较。采用免疫分析法测定血清甲基乙二醛衍生的1-氢咪唑啉酮。通过超声评估颈动脉内膜中层厚度、用杨氏模量评估动脉僵硬度以及用C反应蛋白评估炎症反应来评价动脉粥样硬化。

结果

与对照组相比，糖尿病组甲基乙二醛衍生的1-氢咪唑啉酮显著升高，分别为155.3（标准差（SD）=41.0）U/mL和143.0（SD = 35.1）U/mL，p = 0.003，C反应蛋白也是如此，中位数分别为0.51（0.27，1.83）mg/L和0.31（0.19，0.67）mg/L，p < 0.001。两组在颈动脉内膜中层厚度或杨氏模量方面无显著差异。多元回归分析显示糖尿病组中甲基乙二醛衍生的1-氢咪唑啉酮与C反应蛋白之间存在显著正相关。