TY - JOUR
T1 - Type 1 Diabetes Patients With Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation
AU - Taylor, Guy S.
AU - Shaw, Andy
AU - Scragg, Jadine H.
AU - Smith, Kieran
AU - Campbell, Matthew D.
AU - McDonald, Timothy J.
AU - Shaw, James A.
AU - Ross, Mark D.
AU - West, Daniel J.
N1 - Funding Information:
The authors thank the study participants for their time, effort, and commitment, as well as the research teams at the Newcastle National Institute for Health Research Clinical Research Facility, Newcastle-upon-Tyne, for their assistance with data collection, and the Newcastle University Flow Cytometry Core Facility (FCCF) for assistance with the generation of Flow Cytometry data.
Funding Information:
This study was funded by the Diabetes Research and Wellness Foundation (SCA/OF/12/15) award to DW. Funding was also provided by philanthropic award to DW from the Francis James Bell Endowment Fund, Country Durham Community Foundation. The study funders was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report
Publisher Copyright:
Copyright © 2022 Taylor, Shaw, Scragg, Smith, Campbell, McDonald, Shaw, Ross and West.
PY - 2022/2/11
Y1 - 2022/2/11
N2 - 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; Cpepund), 10 high C-peptide (Cpephigh; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% (Formula presented.). 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 Cpephigh and control groups (+34-121% across phenotypes, p<0.04); but Cpepund group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpepund counts were still lower than Cpephigh 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.
AB - 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; Cpepund), 10 high C-peptide (Cpephigh; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% (Formula presented.). 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 Cpephigh and control groups (+34-121% across phenotypes, p<0.04); but Cpepund group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpepund counts were still lower than Cpephigh 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.
KW - endothelial progenitor cells
KW - exercise
KW - exercise-induced mobilisation
KW - haematopoietic progenitor cells
KW - residual beta-cell function
UR - http://www.scopus.com/inward/record.url?scp=85125253936&partnerID=8YFLogxK
U2 - 10.3389/fendo.2022.797438
DO - 10.3389/fendo.2022.797438
M3 - Article
C2 - 35222269
AN - SCOPUS:85125253936
SN - 1664-2392
VL - 13
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 797438
ER -
