680-P: Residual ß-Cell Function in Long-Term Type 1 Diabetes Is Associated with a Fivefold Greater Mobilization of Endothelial Progenitor Cells after Exercise

Aims: β-cells can function for years after diagnosis in people with type 1 diabetes (T1D). It is unknown how C-peptide secretion impacts upon rare blood vessel protecting Endothelial and Hematopoietic Progenitor Cells (EPCs and HPCs), particularly in response to cardiovascular stress, such as exercise. We compared EPC and HPC counts at rest and after acute exercise in clinically diagnosed people with T1D with undetectable and high C-peptide.

Methods: After quantification of stimulated C-peptide, 11 participants with undetectable C-peptide (Cpep_und <3 pmol/L) and 10 with high C-peptide (Cpep_high >200 pmol/L) were recruited, with no differences in age, fitness or HbA1c, while the Cpep_high group had shorter diabetes duration (27±13 vs. 11±3 years, p=0.01). After a maximal exercise test, participants attended a third visit to complete 45mins of walking at 60%VO_2peak. Blood samples were taken at rest, immediately and 1 hour post exercise. Two HPC and five EPC phenotypes were enumerated by flow cytometry. Data (mean±SD) were analysed by two-way ANOVA and t-test with significance accepted at p≤0.05.

Results: The Cpep_high group displayed higher rest values of HPCs than the Cpep_und group, and increased rest to post exercise mobilization (p<0.05). While resting counts were similar, exercise mobilized all EPC phenotypes in the Cpep_high group with no significant changes in the Cpep_und group. CD34⁺CD45^dimVEGFR2⁺ EPCs did not differ at rest (Cpep_high 28±13 vs. Cpep_low 22±7 cells/ml, p=0.22), while Cpep_high increased from rest to post exercise by 25±22 vs. 5±15 cells/ml in the Cpep_und group (p=0.02).

Conclusion: People with T1D who maintained a high residual β-cell function had increased counts of HPCs and EPCs, and sustained a >5 fold exercise mobilization of EPCs compared to people with no C-peptide. Future research needs to understand if these differences are due to clinical characteristics or the potential direct impact of C-peptide upon vasculature.