phosphocreatine and Metabolic-Syndrome

Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients.. Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [(18)F]-2-fluoro-2-deoxy-D-glucose and [(11)C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (P<0.001).. In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.

Topics: Adenosine Triphosphate; Aged; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Acids; Glycated Hemoglobin; Heart; Humans; Hypoglycemic Agents; Insulin Resistance; Liver; Male; Metabolic Syndrome; Metformin; Middle Aged; Myocardium; Phosphocreatine; Pioglitazone; PPAR alpha; Radionuclide Imaging; Stroke Volume; Sulfonylurea Compounds; Thiazolidinediones; Triglycerides; Ventricular Dysfunction, Left; Ventricular Remodeling

Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex- and activity-matched control subjects to assess the aerobic capacity. We performed (31)phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO(2); 34.1±6.2 vs. 41.4±8.4 ml kg(-1) min(-1), P<0.05) and anaerobic threshold (AT; 18.0±2.4 vs. 23.1±3.7 ml kg(-1) min(-1), P<0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO(2) (r=-0.64) and AT (r=-0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO(2) (r=-0.47) and AT (r=-0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r=0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism.

Topics: Adult; Body Mass Index; Energy Metabolism; Exercise; Exercise Test; Humans; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Middle Aged; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine; Waist Circumference

Topics: Adenosine Triphosphate; Adult; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Energy Metabolism; Fourier Analysis; Humans; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Middle Aged; Myocardium; Phosphocreatine; Phosphorus Isotopes; Signal Processing, Computer-Assisted