Insulin resistance and endothelial function in children and adolescents.

AIMS: Insulin resistance (IR) impairs cellular response to insulin due to a dysfunction in glucose metabolism, associated with an increased cardiovascular risk. The aim of our study was to investigate the relationship among homeostasis model assessment index (HOMA index), endothelial function and vascular morphology in order to better stratify cardiovascular risk in children and adolescents. METHODS: A total of 150 children and adolescents (55 pre-pubertal, mean age 10.4 ± 3.1 years) were enrolled. Anthropometric [body mass index (BMI), waist circumference (WC)], laboratory [blood lipids, inflammatory markers, insulinemia, glycemia], HOMA index and ultrasound parameters [flow-mediated dilatation (FMD), common carotid intima-media thickness (cIMT) and antero-posterior diameter of infra-renal abdominal aorta (APAO)] were assessed. RESULTS: cIMT was positively related to age (r=0.274, p<0.01), BMI (r=0.318, p<0.01), WC (r=0.315, p<0.01) and triglycerides (r=0.230, p<0.01). APAO measurements showed a linear positive correlation with age (r=0.435, p<0.01), BMI (r=0.505, p<0.01), WC (r=0.487, p<0.01), triglycerides (r=0.280, p<0.01), C-reactive protein (r=0.209, p<0.05), fasting insulin (r=0.378, p<0.01) and HOMA index (r=0.345, p<0.01). FMD was inversely related to age (r=-0.251, p<0.01), rough BMI (r=-0.318, p<0.01), WC (r=-0.340, p<0.01), fasting insulin (r=-0.281, p<0.01) and HOMA index (r=-0.282, p<0.01). Multiple regression analysis found no influence of HOMA index on APAO and cIMT. HOMA index was an independent predictor for brachial artery FMD worsening after the statistical adjustment. CONCLUSION: HOMA index increase induced a worsening in endothelial function since childhood.

Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.

BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.