Endothelial progenitor cells are related to glycemic control in children with type 1 diabetes over time

Abstract

Objective: The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control.

Research design and methods: Children (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated.

Results: EPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = -0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of -4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period.

Conclusions: This is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.

Figure 1

CPCs and EPCs in patients with T1DM. CO, control subjects. An α level of P < 0.05 (two-tailed) is considered statistically significant.

Figure 2

Association of all EPC data with all HbA_1c data. An α level of P < 0.05 (two-tailed) is considered statistically significant. Middle line is line of fit. The two additional lines are 95% CIs.

Figure 3

Association of ΔEPCs with ΔHbA_1c. An α level of P < 0.05 (two-tailed) is considered statistically significant. Middle line is line of fit. The two additional lines are 95% CIs.