Type 1 Diabetes Patients With Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation

Background: Many individuals with type 1 diabetes retain residual beta-cell function. Sustained endogenous insulin and C-peptide secretion is associated with reduced diabetes related complications, but underlying mechanisms remain unclear. Lower circulating numbers of endothelial and hematopoietic progenitor cells (EPCs and HPCs), and the inability to increase the count of these cells in response to exercise, are also associated with increased diabetes complications and cardiovascular disease. It is unknown whether residual beta-cell function influences HPCs and EPCs. Thus, this study examined the influence of residual beta-cell function in type 1 diabetes upon exercise-induced changes in haematopoietic (HPCs) and endothelial progenitor cells (EPCs). Methods: Participants with undetectable stimulated C-peptide (n=11; Cpep(und)), 10 high C-peptide (Cpep(high); > 200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% (V) over dotO(2peak) . Clinically significant HPCs (CD34(+)) and EPCs (CD34(+)VEGFR2(+)) phenotypes for predicting future adverse cardiovascular outcomes, and subsequent cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), were enumerated at rest and immediately post-exercise by flow cytometry. Results: Exercise increased HPCs and EPCs phenotypes similarly in the Cpep(high) and control groups (+34-121% across phenotypes, p < 0.04); but Cpep(und) group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpep(und) counts were still lower than Cpep(high) at rest. Conclusions: Residual beta-cell function is associated with an intact exercise-induced HPCs and EPCs mobilisation. As key characteristics (age, fitness, HbA1c) were similar between groups, the mechanisms underpinning the absent mobilisation within those with negative C-peptide, and the vascular implications, require further investigation.

Automated summary

This study found that residual beta-cell function in individuals with type 1 diabetes is associated with increased production of hematopoietic and endothelial progenitor cells in response to exercise. Despite an increase in these cells after exercise in diabetes patients, those without residual beta-cell function still had lower cell counts compared to those with residual beta-cell function at rest.