Abstract 1719: Pioglitazone Improves Aerobic Capacity and Skeletal Muscle High-Energy Phosphate Metabolism in Patients With Metabolic Syndrome
Background: Lowered aerobic capacity is a strong predictor for cardiovascular morbidity and mortality. The aerobic capacity is impaired in patients with metabolic syndrome (MetS) which is associated with the abnormal skeletal muscle high-energy phosphate metabolism. Pioglitazone ameliorates glucose intolerance in these patients via its insulin sensitizing action. However, the effects of pioglitazone on skeletal muscle energy metabolism remain largely unexplored.
Hypothesis: We thus hypothesized that pioglitazone could increase the aerobic capacity in relation to the improvement of skeletal muscle energy metabolism in MetS.
Methods: The incremental exercise tests with a cycle ergometer were performed in 8 male patients with MetS, and 8 age-, sex-, and activity-matched control subjects. Peak oxygen uptake (peak VO2) and anaerobic threshold (AT) were adjusted by lean body mass to exclude the differences of body weight between groups. 31P-magnetic resonance spectroscopy was performed to measure skeletal muscle high-energy phosphate metabolites including phosphocreatine (PCr) during unilateral plantar flexion (0.67Hz for 4 min) with a constant load of 20% one-repetition-maximum. These measurements were repeated after 4 months of pioglitazone (15 mg/day) treatment in MetS.
Results: Peak VO2 (33.0 ± 5.7 vs 42.4 ± 8.7 mL/kg/min, P < 0.05) and AT (18.6 ± 3.0 vs 24.1 ± 3.6 mL/kg/min, P < 0.01) were significantly lower in MetS than control in association with an increase in PCr loss (38 ± 11 vs 18 ± 6%, P < 0.01). Pioglitazone significantly decreased fasting blood glucose (115 ± 16 vs. 103 ± 12 mg/dl, P < 0.05) and plasma insulin (12.4 ± 5.7 vs. 6.5 ± 3.0 μIU/ml, P < 0.05) without affecting body weight and percent body fat. It also increased peak VO2 (36.2 ± 5.9 mL/kg/min) and AT (20.3 ± 3.4 mL/kg/min) and decreased PCr loss (31 ± 9%). There was an inverse correlation between peak VO2 and PCr loss (r = −0.58, P < 0.01), and between AT and PCr loss (r = −0.41, P < 0.05) obtained from MetS and control subjects.
Conclusions: Pioglitazone improved the aerobic capacity and skeletal muscle high-energy phosphate metabolism in MetS. Pioglitazone could improve not only the insulin sensitivity but also the mitochondrial energy production regulated by the skeletal muscle.