Anna Di Sessa

Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children

Bisphenol A (BPA) exposure has been associated with increased incidence of diabetes and obesity in adults.

Bioavailable Vitamin D in Obese Children: The Role of Insulin Resistance.

CONTEXT Studies examining vitamin D levels in association with childhood obesity usually do not consider the effect of insulin on vitamin D-binding protein and do not calculate the unbound, bioavailable vitamin D. OBJECTIVE This study aimed to evaluate in a group of children 1) the concentrations of both total 25-hydroxyvitamin D and bioavailable fraction, and 2) the potential role of insulin resistance in modulating the concentrations of bioavailable vitamin D. Design, Setting, and Patients or Other Participants: This was a cross-sectional study at a University Pediatric Department in which 63 obese children and 21 lean controls were enrolled. MAIN OUTCOME MEASURES Total 25-hydroxyvitamin D and vitamin D-binding protein were measured, two single-nucleotide polymorphisms in the coding region of the vitamin D-binding protein (rs4588 and rs7041) were studied, and the vitamin D bioavailable fraction was calculated. RESULTS Obese children showed total 25-hydroxyvitamin D levels lower compared with nonobese children (21.3 ± 6.7 ng/mL vs 29.6 ± 11.7 ng/mL; P = .0004). Bioavailable 25-hydroxyvitamin D levels were not different among the two groups (3.1 ± 1.6 ng/mL vs 2.6 ± 1.2 ng/mL; P > .05). Insulin-resistant children showed higher bioavailable levels of 25-hydroxyvitamin D compared with noninsulin-resistant children (3.4 ± 1.4 ng/mL vs 2.0 ± 0.9 ng/mL; P = .013) and an inverse correlation between insulin resistance and vitamin D-binding protein was found (r:= -0.40; P = .024). CONCLUSIONS Obese children present levels of bioavailable 25-hydroxyvitamin D similar to those of normal-weight children due to reduced concentration of vitamin D-binding protein. The insulin resistance could play a role in this reduced concentration.

From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction.

Novel association between the nonsynonymous A803G polymorphism of the N‐acetyltransferase 2 gene and impaired glucose homeostasis in obese children and adolescents

The N‐acetyltransferase 2 ( NAT2 ) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin‐resistance‐related traits.

The rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth

Objectives:Non alcoholic fatty liver disease (NAFLD) is a leading cause of liver damage in childhood, its occurrence is influenced by genetic and environmental factors. Recently, the rs626283 polymorphism in the MBOAT7 gene has been found to be associated with alcoholic liver disease and NAFLD in adults.Methods:In a multiethnic cohort of obese children and adolescents we genotyped the rs626283 polymorphism in the MBOAT7 gene, evaluated insulin sensitivity by an oral glucose tolerance test, and measured the intra-hepatic fat content (HFF%) by magnetic resonance imaging.Results:In Caucasian youth, the minor allele (C) was associated with HFF% in (P=0.003), fasting insulin (P=0.03), area under the curve of glucose (P=0.03), and lower degree of whole-body insulin sensitivity (P=0.01) independent of age, gender, and body mass index z-score. A partial correlation showed that the association between the rs626283 variant and insulin resistance was driven by the presence of hepatic steatosis (P=0.009). However, there was no association between the rs626283 and hepatic steatosis among Hispanic and African American children and youth. The association between the rs626283 in the MBOAT7 gene among Caucasians was independent of the PNPLA3 rs738409, GCKR 1260326, and TM6SF2 rs58542926 (P=0.01). The four polymorphisms combined explained~19% of the HFF% in Caucasian obese children and adolescents.Conclusions:The rs626283 variant in the MBOAT7 gene is associated with NAFLD and may affect glucose metabolism by modulating intra-hepatic fat content in Caucasian obese children and adolescents.

Association between 14 bp insertion/deletion HLA-G functional polymorphism and insulin resistance in a cohort of Italian children with obesity

The non‐classical HLA‐class I molecule‐g (HLA‐G) gene shows a deletion/insertion (del/ins) polymorphism of a 14‐base‐pair sequence (14 bp) in the exon 8 at the 3′ untranslated region. The presence of the 14 bp insertion allele has been associated to lower soluble HLA‐G protein production, a protein with anti‐inflammatory activities. So far, no studies have investigated the relationship between HLA‐G 14 bp del/ins polymorphism and metabolic features of obese children and adolescents. We aimed to assess if the HLA‐G ins/del polymorphism, and in particular the HLA‐G ins/ins genotype determining lower sHLA‐G production, is associated to insulin resistance (evaluated by homeostasis model assessment [HOMA]) in a population of obese children.

Atopy as a risk factor for subclinical hypothyroidism development in children.

Abstract Background: Increased thyroid stimulating hormone (TSH) serum concentration can be a marker of subclinical hypothyroidism (SCH) or transient hyperthyrotropinemia. The aim of our study was to evaluate whether high serum TSH concentrations in allergic children could represent true SCH or isolated and transient hyperthyrotropinemia. Methods: We enrolled 620 allergic children (1.11–12.8 years) consecutively attending to our department. They were classified as atopics and non-atopics on the basis of the atopy work-up and, at baseline, they were investigated for thyroid function and low-grade inflammation state. Further, TSH was evaluated after 6 (T1) and 12 (T2) months. Results: Both atopics and non-atopics showed higher SCH prevalence compared to controls (p=0.0055 and p=0.02, respectively), and a significant association between atopy and SCH (OR 10.11, 95% CI 1.36–75.12) was found. Both at T1 and T2, atopics had a significant risk of developing severe SCH compared to non-atopics (RR 1.8, 95% CI 1.39–2.34 and 1.61, 95% CI 1.21–2.14; respectively). Conclusions: Our data may suggest that hyperthyrotropinemia in atopic children could be used as a marker of true SCH.

The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.