A Six-Week Home Exercise Program Improves Endothelial Function and CD34+ Circulating Progenitor Cells in Patients With Pre-Diabetes

Abstract

Background: Pre-diabetes is associated with endothelial dysfunction and affects endothelium-associated stem cells. Lifestyle modification has been shown to prevent the progression from pre-diabetes to overt type 2 diabetes; however, the effect of such interventions on CD34⁺ progenitor cells in pre-diabetes participants has not been tested. The purpose of this study was to determine whether a home-based 6-week exercise intervention improved vascular function, circulating number, function, and gene expression of circulating CD34⁺ progenitor cells in patients with pre-diabetes.

Methods: Patients (40 - 70 years, BMI of 25 - 39.9, n = 11) were enrolled in a 16-week randomized crossover study that consisted of 6 weeks each of an exercise (150 minutes/week) and non-exercise phase with a 4-week washout between phases. Adherence to the exercise regimen was monitored by accelerometry. All participants were encouraged to follow a low fat/low calorie diet throughout the 16 weeks. Endothelial function was assessed via brachial artery flow mediated dilatation (FMD) and CFU-Hill colony formation. CD34⁺ cell number, migratory function, gene expression, and serum inflammatory markers were evaluated.

Results: With the intervention, endothelial function improved (FMD, 5.70.6% to 11.20.9%, CFU-Hill, 3.30.2% to 8.20.6%, both P < 0.05). There was a significant reduction in cholesterol, triglyceride, insulin, leptin, interleukin-6 (IL-6), low density lipoprotein (LDL), apolipoprotein B (ApoB) and increase in apolipoprotein A1 (ApoA1) with the lifestyle intervention (all P < 0.05). An increase in circulating CD34⁺ cells (P < 0.005), decrease in CD34⁺ endothelin-1, IL-6, tumor necrosis factor (TNF)-alpha, p53, and p21 gene expression (all P < 0.05), and improved migration toward stromal cell derived factor (SDF)-1alpha occurred with the intervention.

Conclusion: The improvements in endothelial function and CD34⁺ circulating progenitor cells in patients with pre-diabetes indicate that pre-diabetes may be a clinical window of therapeutic opportunity for lifestyle interventions.




J Endocrinol Metab. 2015;5(1-2):163-171
doi: http://dx.doi.org/10.14740/jem273w