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早期强化胰岛素治疗对新诊断2型糖尿病患者内皮祖细胞的影响

Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes.

作者信息

Zhang Wei, Wang Hongdong, Liu Fangcen, Ye Xiao, Tang Wenjuan, Zhang Pengzi, Gu Tianwei, Zhu Dalong, Bi Yan

机构信息

Department of Endocrinology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

出版信息

Diabetes Ther. 2022 Apr;13(4):679-690. doi: 10.1007/s13300-021-01185-w. Epub 2021 Dec 11.

Abstract

AIM

This study aimed to investigate the alteration of circulating CD34KDRCD133 endothelial progenitor cells (EPCs) in patients with newly diagnosed type 2 diabetes and the mechanism of the effect of early intensive insulin therapy.

METHODS

In this study, 36 patients with newly diagnosed type 2 diabetes and 22 control subjects matched by age and gender were enrolled. All of the patients with diabetes received intensive insulin therapy. The number of EPCs was assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR).

RESULTS

Levels of circulating CD34KDRCD133 EPCs were higher in patients with diabetes compared to control subjects and significantly decreased after intensive insulin therapy. Levels of vascular endothelial growth factor (VEGF), a major contributor to EPC mobilization, were significantly higher in patients with diabetes compared to control subjects, and dramatically decreased after insulin therapy. Importantly, VEGF levels correlated with number of EPCs. Moreover, compared with control subjects, pro-inflammatory cytokines and oxidative stress were significantly higher in patients with diabetes and markedly decreased after intensive insulin therapy.

CONCLUSIONS

These results showed that type 2 diabetes is associated with an increase of circulating CD34KDRCD133 EPCs at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserving effect on EPC level partly through improving inflammation status and oxidative stress, thereby implying a putative long-term beneficial effect on vascular integrity via suspending excessive EPC exhaustion.

CLINICAL TRIAL NUMBER

NCT03710811.

摘要

目的

本研究旨在调查新诊断2型糖尿病患者循环中CD34⁺KDR⁺CD133⁺内皮祖细胞(EPCs)的变化以及早期强化胰岛素治疗的作用机制。

方法

本研究纳入了36例新诊断的2型糖尿病患者和22例年龄及性别匹配的对照者。所有糖尿病患者均接受强化胰岛素治疗。基于CD34、CD133和含激酶插入结构域受体(KDR)的表达,通过流式细胞术评估EPCs数量。

结果

与对照者相比,糖尿病患者循环中CD34⁺KDR⁺CD133⁺EPCs水平更高,强化胰岛素治疗后显著降低。血管内皮生长因子(VEGF)是EPC动员的主要促成因素,与对照者相比,糖尿病患者的VEGF水平显著更高,胰岛素治疗后显著降低。重要的是,VEGF水平与EPCs数量相关。此外,与对照者相比,糖尿病患者的促炎细胞因子和氧化应激显著更高,强化胰岛素治疗后明显降低。

结论

这些结果表明,2型糖尿病在发病时与循环中CD34⁺KDR⁺CD133⁺EPCs增加有关,提示代偿性动员增加。此外,早期强化胰岛素治疗部分通过改善炎症状态和氧化应激对EPC水平发挥保护作用,从而暗示对血管完整性可能有长期有益影响,可防止过度的EPC耗竭。

临床试验编号

NCT03710811。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0ba/8991286/d273d8b12837/13300_2021_1185_Fig1_HTML.jpg

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