Enhanced external counterpulsation improves peripheral artery function and glucose tolerance in subjects with abnormal glucose tolerance

Martin JS, Beck DT, Aranda JM Jr., Braith RW. Enhanced external counterpulsation improves peripheral artery function and glucose tolerance in subjects with abnormal glucose tolerance. J Appl Physiol 112: 868-876, 2012. First published December 22, 2011; doi:10.1152/japplphysiol.01336.2011.-Background: in coronary artery disease patients, enhanced external counterpulsation (EECP) improves peripheral arterial function and nitric oxide (NO) bioavailability, which have been implicated in the pathogenesis of abnormal glucose tolerance (AGT). We sought to evaluate the effects of EECP on outcomes of arterial function, glucose tolerance, and skeletal muscle morphology in subjects with AGT. Methods and Results: 18 subjects with AGT were randomly (2: 1 ratio) assigned to receive either 7 wk (35 1-h sessions) of EECP (n = 12) or 7 wk of standard care (control; n = 6). Peripheral vascular function, biochemical assays, glucose tolerance, and skeletal muscle morphology were evaluated before and after EECP or control. EECP increased normalized brachial artery (27%) and popliteal artery (52%) flow-mediated dilation. Plasma nitrite/nitrate (NOx) increased (30%) and 8-isoprostane-PGF-F2(alpha), a marker of lipid peroxidation in the plasma, decreased (-23%). Fasting plasma glucose declined (-16.9 +/- 5.4 mg/dl), and the homeostasis model assessment of insulin resistance (HOMA-IR) decreased (31%) following EECP. Plasma glucose 120 min after initiation of oral glucose tolerance testing decreased (-28.3 +/- 7.3 mg/dl), and the whole body composite insulin sensitivity index (C-ISI) increased (21%). VEGF concentrations increased (75%), and vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density following EECP. No change was observed in cellular signaling pathways, but there was a significant increase GLUT-4 protein expression (47%) following EECP. Conclusions: our findings provide novel evidence that EECP has a beneficial effect on peripheral arterial function and glucose tolerance in subjects with AGT.