Abstract 230: Effect of aerobic exercise on Endothelial Progenitor Cells (EPCs) in patients with prediabetes

Abstract

Introduction At least 79 million Americans have pre-diabetes. Though life-style modification prevents progression from Pre-diabetes to overt diabetes, the effect on vascular endothelial progenitor cells (EPC) stem cells is unknown. Methods This is a crossover study of 16-week duration, using exercise-naive pre-diabetes patients, n=12, aged 45-65 yrs with a BMI of 25-34.9. We studied flow mediated dilatation (FMD), EPC function and gene expression and serum endothelial inflammatory levels after 6 weeks each of aerobic exercise (150min/week) and non exercise phase, in a cross over design with 4 week wash-out period between the 2 phases. EPC migration was noted in response to chemotactic factors such as Vascular Endothelial Growth Factor (VEGF-A, 0- 50ng/ml) and Stromal Cell-Derived Factor-1(SDF1α, 0-100 ng/ml). Exercise compliance was monitored by regular phone calls and downloadable accelerometers. Results FMD studies (undertaken by 3 observers) showed mean FMD in non-exercise group of 5.7+0.6% which improved to 11.2+0.9% post-exercise. No significant weight loss noted between the 2 groups, however, significant reduction in leptin, IL-6, TNFα, hs-CRP, Triglyceride, and ApoB levels was noted. EPC gene expression analysis showed decrease of eNOS (5 fold) and increase of PECAM-1 (4-fold), Endothelin-1 (3-fold), IL-6 (2-fold), TNFα (3-fold) in non-exercise which improved following exercise. EPC migration improved post exercise, particularly in response to SDF-1α as did CD34+ cell number and EPC colony formation improved significantly also. Conclusion We demonstrate that pre-diabetic state is associated with poor vascular reactivity and impaired EPC stem cell function. Pre-diabetes may be a clinical window of therapeutic intervention opportunity when short course of aerobic exercise may allow improvement of vascular reactivity and EPC function despite no statistically significant weight loss. This study also indicates EPCs may act as an important biomarker for vascular function.