The Role of Endothelial Progenitor Cells (EPCs) and Circulating Endothelial Cells (CECs) as Early Biomarkers of Endothelial Dysfunction in Children with Newly Diagnosed Type 1 Diabetes

Abstract

The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients' clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients' condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D.

Keywords: children; endothelial function; type 1 diabetes; vascular complications.

Figure 1

Gating strategy of endothelial progenitors and circulating cells. Selection of CD34+ cells within cells, with the morphology of mononuclear cells based on FSC and SSC properties. Subsequent gates set on CD309+ and CD133+ (for EPCs) or CD144+ (for CECs) using Boolean gating were implemented. All necessary fluorescence minus one (FMO) (red) or unstained controls are demonstrated.

Figure 2

Comparison of (a,b) CECs—circulating endothelial cells, (c,d) EPCs—endothelial progenitor cells, and (e) EPC/CEC ratio between T1D patients and the control group. Statistically significant p values are presented. (T1D—type 1 diabetes, Control—control group).

Figure 3

Comparison of (a) CECs—circulating endothelial cells, (b) EPCs—endothelial progenitor cells, and (c) EPC/CEC ratio depending on T1D patients’ clinical conditions at the disease onset. Statistically significant p values are presented.

Figure 4

Representation of the mechanism by which elevated levels of EPCs may serve as a potential early indicator of endothelial dysfunction in individuals with type 1 diabetes.