Abstract MP74: Use of Cd34+ Cells as a Cellular Biomarker in Prediabetes Subjects, Post Aerobic Exercise
Introduction: Pre-diabetes has been associated with endothelial dysfunction that may affect both endothelium and stem cells. We hypothesized that aerobic exercise can improve function and gene expression of hemopoetic stem cells (CD34+ cells)in pre-diabetes. Though life-style modification has been shown to prevent progression from Pre-diabetes to overt diabetes, the effect of exercise on endothelium in pre-diabetes has not been tested. Also use of CD34+ cells as biomarker is novel.
Methods: This is a crossover study of 16-week duration, using exercise-naive pre-diabetes patients, aged 40-70 yrs with a BMI of 25-39.9, n=11. We studied their flow mediated dilatation (FMD), CD34+ cell function, gene expression and serum endothelial inflammatory markers after 6 weeks each of aerobic exercise (150min/week) and non-exercise phase, with 4 week wash-out period between the 2 phases. We tested migration in response to chemotactic factors VEGF-A(50ng/ml) and SDF1alpha(0,10 and 100 ng/ml). We also assessed Hill colony formation. Adherence to exercise regimen was monitored by regular phone calls and downloadable accelerometers (actigraphs).
Results: There was no statistically significant weight loss in post exercise phase. FMD studies (by 3 observers) showed mean FMD of 5.7±0.6% which improved to 11.2±0.9% post-exercise. Biochemistry showed significant reduction in leptin, Triglyceride, Apo-B, ApoA1 levels and inflammatory markers, IL-6, TNF alpha & hs-CRP. CD34+ cell gene expression analysis showed increase in eNOS (2.5 fold)and VEGF-A (2 fold)and reduction in Endothelin-1 (3-fold), IL-6 (2.4-fold reduction), TNF (3-fold ) following exercise. CD34+ migration improved post exercise, particularly in response to 10ng/ml SDF-1. Hill Colony Counts doubled post exercise.
Conclusion: We demonstrate that pre-diabetic state is associated with poor vascular reactivity and impaired CD34+ cell number, function and gene expression. However, significant improvement in FMD may indicate that Pre-diabetes state may also be the clinical window of therapeutic opportunity when interventions such as aerobic exercise can prevent progression of endothelial dysfunction.
The study also demonstrates that CD34+ cell can serve as a useful cellular bio-marker in pre-diabetes and possibly early diabetes patients.
Author Disclosures: S. Sen: None. A. Islam: None.
- © 2015 by American Heart Association, Inc.