Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Front Endocrinol (Lausanne). 2022 Feb 11;13:797438. doi: 10.3389/fendo.2022.797438. eCollection 2022.
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).
Participants with undetectable stimulated C-peptide (n=11; Cpep), 10 high C-peptide (Cpep; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% . Clinically significant HPCs (CD34) and EPCs (CD34VEGFR2) 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.
Exercise increased HPCs and EPCs phenotypes similarly in the Cpep and control groups (+34-121% across phenotypes, p<0.04); but Cpep group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpep counts were still lower than Cpep at rest.
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.
许多 1 型糖尿病患者仍保留有β细胞功能。持续的内源性胰岛素和 C 肽分泌与减少糖尿病相关并发症有关，但潜在机制尚不清楚。循环中内皮和造血祖细胞（EPCs 和 HPCs）数量较低，以及在运动刺激下无法增加这些细胞的数量，也与增加糖尿病并发症和心血管疾病有关。目前尚不清楚残余β细胞功能是否会影响 HPC 和 EPC。因此，本研究检测了 1 型糖尿病患者残余β细胞功能对运动诱导的造血（HPC）和内皮祖细胞（EPC）变化的影响。
本观察性运动研究纳入了 11 名 C 肽刺激后无法检测到（Cpep）、10 名 C 肽高（Cpep；>200pmol/L）和 11 名非糖尿病对照组的参与者，他们完成了 45 分钟 60%最大步行强度的剧烈运动。通过流式细胞术，在休息和运动后即刻检测预测未来不良心血管结局的临床显著 HPC（CD34）和 EPC（CD34VEGFR2）表型，以及趋化因子受体 4（CXCR4）和 7（CXCR7）的细胞表面表达。
Cpep 组和对照组的运动均可使 HPC 和 EPC 表型相似地增加（各表型增加 34-121%，p<0.04）；但 Cpep 组在休息时并未显著增加，即使在控制糖尿病病程后也是如此。值得注意的是，运动后的 Cpep 计数仍低于休息时的 Cpep。
残余β细胞功能与完整的运动诱导 HPC 和 EPC 动员有关。由于组间的关键特征（年龄、体能、HbA1c）相似，因此需要进一步研究那些 C 肽阴性患者中缺乏动员的潜在机制及其对血管的影响。
