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Manco M.,Research Unit for Multifactorial Disease | Morandi A.,University of Verona | Marigliano M.,University of Verona | Rigotti F.,University of Verona | And 2 more authors.
Atherosclerosis | Year: 2013

Objective: To assess the cross-sectional association of epicardial fat with insulin resistance, major abdominal adipose depots, and cardiovascular disease (CVD) risk factors in obese pre-pubertal and early pubertal children. Methods: By using magnetic resonance imaging in 30 pre-pubertal and early pubertal patients [21 males, Tanner Stage I-II, median age 11.2 (2.95) y, BMI z-score 2.56 ± 0.11 SDS], visceral (VAT), subcutaneous (SAT), epicardial adipose tissues (EAT) and hepatic fat fraction (HFF) were estimated. Lipid profile, liver function tests, circulating adipokines and markers of inflammation [leptin, adiponectin, tumor necrosis factors-alpha (TNF-alpha), C-reactive protein (CRP), interleukins 6 and 10 (IL-6, IL-10)] were assayed. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Body composition was measured by dual-energy X-ray absorptiometry. Results: In 14 insulin resistant children (HOMA-IR >2.5), median values of EAT were significantly higher than in insulin sensitive mates [54.0 (35.45) cm3 vs. 27.2 (17.03) cm3; p = 0.03]. Moreover, EAT performed no differently in identifying insulin resistant patients (AUC 0.737; 95% CI 0.538-0.936; p = 0.028) from VAT (AUC 0.772; 95% CI 0.599-0.945; p = 0.011); SAT (AUC 0.795; 95% CI 0.628-0.0.962; p = 0.006); and HFF (AUC 0.777; 95% CI 0.607-0.947; p = 0.010). Stepwise regression analysis showed that EAT (β = 0.025; 95% CI 0.012-0.038, p = 0.001) and CRP (β = 0.622; 95% CI 0.069-0.238, p = 0.002) predicted HOMA-IR (R2 = 0.71; p = 0.001), while VAT, SAT and HFF were excluded from the model. Conclusions: In pre-pubertal and early pubertal obese children, EAT is a significant marker of increased insulin resistance and associated cardiovascular risk. © 2012 Elsevier Ireland Ltd.

Brufani C.,Endocrinology and Diabetes Unit | Crino A.,Endocrinology and Diabetes Unit | Fintini D.,Endocrinology and Diabetes Unit | Patera P.I.,Endocrinology and Diabetes Unit | And 2 more authors.
Hormone Research in Paediatrics | Year: 2013

Objective: Childhood obesity has become epidemic and has been accompanied by an increase in prevalence of type 2 diabetes (T2DM) in youth. Addressing obesity and insulin resistance by drug treatment represents a rational strategy for the prevention of T2DM. A systematic review was performed to evaluate the effectiveness of metformin in reducing weight and ameliorating insulin resistance in obese nondiabetic children. Methods: A PubMed database search was conducted, using 'metformin', 'obesity', 'insulin resistance', 'children', 'adolescents' as search terms. Results: Eleven trials were included in the present review. Metformin was administered for 6-12 months at a dosage of 1,000-2,000 mg/daily, decreasing BMI by 1.1-2.7 compared with placebo or lifestyle intervention alone. Concomitantly, fasting insulin resistance improved after metformin therapy. Posttreatment follow-up was performed in one study, showing that after 1 year of discontinuation of therapy the decrease in BMI disappears. Conclusions: Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents, with a concomitant improvement in fasting insulin sensitivity. Further studies with longer treatment period are needed to establish how much metformin can reduce weight and its real utility in preventing T2DM development in pediatric patients. Copyright © 2013 S. Karger AG, Basel.

Iesari S.,Catholic University | Le Roux C.W.,University College Dublin | De Gaetano A.,National Research Council Italy | Manco M.,Research Unit for Multifactorial Disease | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Obesity is characterized by decreased insulin-stimulated glucose uptake in muscle and shift from glucose to lipid oxidation, the so-called metabolic inflexibility. Biliopancreatic diversion (BPD), a mainly malabsorptive bariatric operation, determines a prompt improvement of insulin resistance, but the mechanisms are still unclear. Objective: We aimed to estimate the response of glucose transporter 4 (GLUT4) and hexokinase-II (HKII) gene expression to hyperinsulinemia before and after surgical treatment with a BPD or dietary-induced weight loss. The association with 24-hour energy expenditure and its different components-diet-induced thermogenesis (DIT), resting energy expenditure, physical activity (PA) of daily living, and physical exercise-was also determined. Design, Setting, and Main Outcome Measures: Case-control study: 20 subjects, BPD vs diet-induced weight loss. Four subjects withdrew in the surgical arm and 1 subject withdrew in the dietary arm. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp. Energy expenditure was assessed by indirect calorimetry over 24 hours. Muscle biopsies were obtained during the clamp to measure gene expression: GLUT4 and HKII. Results: Insulin sensitivity increased significantly (P <.01) only after BPD (0.101 ± 0.012 to 0.204 ± 0.033 μmol/kg/min/pM). Enhanced GLUT4 and HKII mRNA levels were observed after surgery (P < .0001 and P = .021, respectively), whereas they were not affected by diet-induced weight loss. Carbohydrate oxidation (P = .0027), DIT (P = .033), PA (P = .036), and energy expenditure during the exercise (P = .017) increased only in the BPD group. Conclusions: BPD improved impaired glucose metabolism and insulin resistance through increased glucose uptake, glycogen synthesis, and glucose oxidation. Furthermore, the concomitant increase in DIT, PA, and exercise in BPD patients may partly explain their ability to sustained long-term weight loss and may contribute to the improved insulin sensitivity. Copyright © 2013 by The Endocrine Society.

Pietrantoni E.,San Camillo Forlanini Hospital | Del Chierico F.,Unit of Metagenomics | Rigon G.,San Camillo Forlanini Hospital | Vernocchi P.,Unit of Metagenomics | And 5 more authors.
International Journal of Molecular Sciences | Year: 2014

Polyunsaturated fatty acids (PUFAs) are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA) are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM) and preterm-PROM (pPROM), are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Masotti A.,Gene expression Microarrays Laboratory Bambino Gesu Childrens Hospital | Baldassarre A.,Gene expression Microarrays Laboratory Bambino Gesu Childrens Hospital | Fabrizi M.,Research Unit for Multifactorial Disease | Manco M.,Research Unit for Multifactorial Disease
Pediatric Obesity | Year: 2016

Background: Circulating microRNAs (miRNAs) may act as biomarkers of metabolic disturbances. Objective: The aim of this study was to identify serum miRNAs signature of early insulin resistance in obese preschoolers. Methods: Twelve obese children, aged 2-6years, six insulin resistant (IR) and six controls were selected being age-matched, sex-matched and body mass index-matched. Profiling of 179 circulating miRNAs, known to be widely expressed in the bloodstream, was investigated by quantitative polymerase chain reaction at fasting and 120min following a standard oral glucose tolerance test (OGTT). Results: Twenty-one miRNAs were differentially regulated in IR obese preschoolers. miR-200c-3p, miR-190a and miR-95 were differently regulated both at fasting and 120min after the OGTT. In controls, the fold changes of some miRNAs were correlated with Δglucose0-120 (miR-660, miR-26b-5p and miR-22-3p: p=0.005 for all) and Δinsulin0-120 (miR-660 and miR-22-3p: p=0.02 for both and miR-423-5p: p=0.042). In IR patients, miR-1 fold changes were correlated with Δglucose0-120 (r=-0.786; p=0.036) and Δinsulin0-120 (r=-0.821; p=0.023). Conclusions: Our study identifies circulating miR-200c-3p, miR-190a and miR-95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers. © 2016 World Obesity.

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