A randomized trial of exercise for blood pressure reduction in type 2 diabetes: effect on flow-mediated dilation and circulating biomarkers of endothelial function.
OBJECTIVE
To investigate the effect of an exercise intervention on flow-mediated dilation (FMD) and circulating endothelial biomarkers in adults with type 2 diabetes (T2DM).


METHODS
Sedentary adults (n = 140), aged 40-65, with T2DM and untreated pre or Stage I hypertension or treated hypertension were randomized to a 6-month, supervised, exercise program (3× week) or a sedentary control. Assessments included BMI, body and visceral fat, blood pressure, lipids, HbA1c, insulin sensitivity (QUICKI), fitness, FMD, E-selectin, P-selectin, intracellular and vascular cellular adhesion molecules (ICAM, VCAM), and tissue plasminogen activator (tPA). Intervention effects were compared by t-tests. Pearson's correlations were calculated between changes in cardiovascular risk factors and endothelial outcomes.


RESULTS
Exercisers significantly improved BMI (-0.6 kg/m(2)), body fat % (-1.4%), HbA1c (-0.5%), and fitness (2.9 mL/kg min) vs. controls (p < 0.05). However, there were no differences between groups in changes in FMD, E-selectin, P-selectin, ICAM, VCAM, or tPA. Among exercisers, changes in cardiovascular risk factors correlated with several biomarkers. Decreased P-selectin correlated with decreased BMI (r = 0.29, p = 0.04) and increased HDL cholesterol (r = -0.36, p = 0.01). Decreased ICAM correlated with decreased triglycerides and HbA1c (r = 0.30, p = 0.04; r = 0.31, p = 0.03) and increased QUICKI (r = - 0.28, p = 0.05). Decreased tPA correlated with decreased total body and visceral fat (r = 0.28, p = 0.05; r = 0.38, p = 0.008) and increased QUICKI (r = -0.38, p = 0.007).


CONCLUSIONS
While exercise resulted in improved fitness, body composition, and glycemic control, there were no changes in FMD or circulating endothelial biomarkers. The associations of changes in cardiovascular risk factors and endothelial biomarkers suggest that improvement in risk factors could mediate the exercise-induced improvements in endothelial function seen in prior studies.
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. bbarone@pitt.edu
Bethany
B
Barone Gibbs
Devon A
DA
Dobrosielski
Susanne
S
Bonekamp
Kerry J
KJ
Stewart
Jeanne M
JM
Clark
D050154:Adiposity; D015142:Baltimore; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005081:Exercise Therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D050152:Intra-Abdominal Fat / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010809:Physical Fitness; D012307:Risk Factors; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation
D015415:Biomarkers; D019040:E-Selectin; D006442:Glycated Hemoglobin; D018799:Intercellular Adhesion Molecule-1; D008055:Lipids; D019007:P-Selectin; D010959:Tissue Plasminogen Activator; D019010:Vascular Cell Adhesion Molecule-1; C546936:SELE protein, human; C546937:SELP protein, human; C517652:hemoglobin A1c protein, human