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

Abstract

Aim

This study aimed to investigate the alteration of circulating CD34⁺KDR⁺CD133⁺ 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 CD34⁺KDR⁺CD133⁺ 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 CD34⁺KDR⁺CD133⁺ 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.