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

Abstract

Objective: Reduced level of endothelial progenitor cells (EPCs) is a critical event in the pathogenesis of vasculopathy in type 2 diabetes. This study aimed to investigate circulating EPCs alteration in newly diagnosed type 2 diabetic patients and how they are affected by early intensive insulin therapy. Methods: Twenty-one newly diagnosed type 2 diabetic patients and 22 control subjects matched by age, gender, and BMI were enrolled. All of the diabetic patients received intensive insulin therapy. EPC numbers were assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor. Results: Level of EPC was higher in diabetic patients compared to control subjects (0.071±0.08% vs. 0.016±0.017%, P<0.001). Notably, EPC number was significantly decreased after therapy (0.007±0.005%, P<0.001 vs. pre-treatment). Level of vascular endothelial growth factor (VEGF), a major contributor of EPC mobilization, was significantly higher in diabetic patients compared to control subjects (26.34±9.15 vs. 17.91±6.6, P=0.002), and decreased dramatically after insulin therapy (21.01±4.64, P=0.0039). Moreover, compared with control subjects, pro-inflammatory cytokines were significantly higher in diabetic patients (TNF-α: 18.74±1.65 vs. 15.7±2.16, P<0.001; IL-1β: 14.04±5.6 vs. 9.41±1.94, P=0.017; IFN-γ: 16.47±3.37 vs. 11.71±3.39, P=0.013) and decreased markedly after insulin therapy (17.27±1.78, P=0.009; 10.81±1.35, P<0.001; 13.72±3.21, P<0.001). Conclusions: These results showed that type 2 diabetes is associated with increased circulating EPC level at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserved effect on EPC level partly through improving inflammation status, thereby implying a putative long term beneficial effect on vascular integrity via suspending excessive EPC exhaustion. Disclosure H. Wang: None. Y. Bi: None. F. Liu: None.