11/11/2016 1 Gustavo Waclawovsky Beatriz D. Schaan 

11/11/2016 2 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 3 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 4 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 5 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 6 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 7 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. 

11/11/2016 8 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. Flow Mediated Dilatation (%) Control Microalbuminuria Normoalbuminuria Type 1 Diabetes 

11/11/2016 9 Type 1 Diabetes (T1DM) Mortality from Ischemic Heart Disease Atherosclerosis Endothelial dysfunction CD34+ CD45dim KDR+ Endothelial progenitor cells Replaces endothelial cells injured Laing SP et al. Diabetologia 2003;46:760-5. Cé GV. J Clin Endocrinol Metab 2011;96:1493-9. Hörtenhuber T. Diabetes Care 2013, 36:1647–1653. CD34+/CD133+/KDR+ (Cells/ 1x106 WBC) Control T1DM 

11/11/2016 10 Fuchsjager-Mayrl G. et al. Diabetes Care 25:1795–1801, 2002. • Bike; • 40 min; • 60-70% HR reserve; • 3 x week. • Bike; • 30 min; • 80% VO2max; • Blood: 20 min. Cubbon RM et al. Arterioscler Thromb Vasc Biol. 2010;30:878-884. Aerobic Exercise: endothelial function in T1DM and progenitor cells in healthy subjects Before training After 4 months * P<0,05 Flow-mediated dilation (% change) * P<0,05 CD34+ CD34+/KDR+ 

11/11/2016 11 To evaluate the acute effect of aerobic exercise (AE) and resistance exercise (RE) on the release of endothelial progenitor cell (EPCs, CD34+/KDR+/CD45dim) and vascular function in T1DM. Purpose Hypothesized Aerobic and resistance exercises would induce a rise in circulating EPCs but lower in patients with diabetes when compared with healthy controls. 

11/11/2016 12 Crossover Clinical Trial T1 DM (n= 14) Healthy subjects (n= 5) Aerobic exercise Resistance exercise Methods Inclusion criteria: • Male sex, • ≥ 18 years old; • Without regular exercise. Exclusion criteria: • Severe autonomic neuropathy; • Diabetic nephropathy; • End stage renal disease; • Disabling peripheral arterial disease; • Proliferative diabetic retinopathy; • Coronary artery disease; • Heart failure; • Limb amputation; • Cancer; • Smoking. randomization (7 days) Cardiopulmonary exercise testing Maximal strength testing (1-RM) 

11/11/2016 13 4 lower-limb exercises; 4 x 12 repetitions; 60% 1-RM; 90 sec (between sets and exercises); 2 sec/phase (concentric and eccentric). 2) Kneed flexion 1) Knee extension 3) Leg press 4) Calf press Resistance exercise session 

11/11/2016 14 4 lower-limb exercises; 4 x 12 repetitions; 60% 1-RM; 90 sec (between sets and exercises); 2 sec/phase (concentric and eccentric). 2) Kneed flexion 1) Knee extension 3) Leg press 4) Calf press Cycle ergometer; 60% VO2peak ; Heart rate monitor and Borg scale 6 to 20. Resistance exercise session Aerobic exercise session 

11/11/2016 15 4 lower-limb exercises; 4 x 12 repetitions; 60% 1-RM; 90 sec (between sets and exercises); 2 sec/phase (concentric and eccentric). • 40 min; • Capillary blood glucose (Baseline and every 10 min); • Glucose levels > 150 mg.dL-1 and e < 250 mg.dL-1. 2) Kneed flexion 1) Knee extension 3) Leg press 4) Calf press Cycle ergometer; 60% VO2peak ; Heart rate monitor and Borg scale 6 to 20. Resistance exercise session Aerobic exercise session 

11/11/2016 16 Flow cytometer (FACSCalibur, BD Biosciences) Progenitor cells (10 min before and 10 min after): • CD34+/CD45dim • CD34+/KDR+/CD45dim 20-mL Analyses 

11/11/2016 17 Venous occlusion plethysmography (DE Hokanson) • Blood flow (10 min before and 5 min after) Vascular resistance (10 min before and 5 min after) • Reactive hyperemia (10 min before and 10 min after) Flow cytometer (FACSCalibur, BD Biosciences) Progenitor cells (10 min before and 10 min after): • CD34+/CD45dim • CD34+/KDR+/CD45dim 20-mL Analyses 

11/11/2016 18 Results 

11/11/2016 19 Results 

11/11/2016 20 Results 

11/11/2016 21 Results 

11/11/2016 22 Results 

11/11/2016 23 Progenitor cells Endothelial progenitor cells * P < 0,05 vs. versus baseline in the same group; † P < 0,05 vs. versus after RE session (group-session interaction); ‡ P < 0,05 vs. versus after AE exercise session. Mean ± SEM; GEE for repeated adjusted for baseline values. 

11/11/2016 24 Forearm blood flow Forearm vascular resistance * P < 0,05 vs. versus baseline in the same group; ‡ P < 0,05 vs. versus after AE exercise session. Mean ± SEM; GEE for repeated adjusted for baseline values. 

11/11/2016 25 Forearm reactive hyperemia * P < 0,05 vs. versus baseline in the same group; Mean ± SEM; GEE for repeated adjusted for baseline values. 

11/11/2016 26 SUMMARY • Exercise did not induce changes in the levels of EPCs in patients with T1DM; • In controls, EPCs were decreased after AE (- 10.7 %, P = 0.017) and increased after RE (+ 12.2 %, P = 0.004); • Blood flow increased and vascular resistance decreased after RE in both groups; • Reactive hyperemia was increased 10 min after AE and RE sessions in patients with T1DM (36.5% and 42.0%, respectively) and in controls (35.4% and 74.3%), but no differences were observed between groups in response to exercise. 

11/11/2016 27 Conclusions The unchanged EPC number in patients with DM1 after exercise sessions may reveal impaired capacity for endothelium regeneration and consequent early deterioration which was not observed by vascular parameters used. 

11/11/2016 28 Gustavo Waclawovsky Beatriz D’ Schaan Obrigado! [email protected] [email protected] FIPE