Cosimo Giannini

Yale University, New Haven, Connecticut, United States

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Publications (57)239.43 Total impact

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    ABSTRACT: Aims/hypothesis With the increase in gestational diabetes mellitus (GDM), there is a growing need to understand the effects of intrauterine glucose exposure on the newborn at birth and later in life. The risk of developing impaired glucose tolerance (IGT) in individuals exposed to diabetes in utero has not been adequately investigated. Methods We studied 255 obese adolescents with normal glucose tolerance. All of them were investigated for in utero exposure to GDM and underwent an OGTT, which was repeated after approximately 2.8 years. Results 210 (82.3%) participants were not exposed to GDM (NGDM group), and 45 (17.7%) were exposed to GDM (EGDM group). In the NGDM group, only 8.6% (n=18) developed either IGT or type 2 diabetes compared with 31.1% (n=14) of the EGDM group who developed either IGT or type 2 diabetes (p<0.001). Exposure to GDM was the most significant predictor of developing IGT or type 2 diabetes (OR 5.75, 95% CI 2.19, 15.07, p<0.001). At baseline and at follow-up, the EGDM group showed a reduction in beta cell function determined by the oral disposition index (p=0.03 and p=0.01, respectively), and, at follow-up, they also displayed a reduction in insulin sensitivity compared with the NGDM group (p=0.05). Conclusions/interpretation Obese youth exposed in utero to GDM show early inability of the beta cell to compensate adequately in response to decreasing levels of insulin sensitivity.
    Diabetologia 08/2014; 57(11). DOI:10.1007/s00125-014-3345-2 · 6.88 Impact Factor
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    ABSTRACT: In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors.
    Diabetes Care 08/2014; 37(11). DOI:10.2337/dc14-0525 · 8.57 Impact Factor
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    ABSTRACT: Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype.
    Allergy, asthma & immunology research 05/2014; 6(3):252-6. DOI:10.4168/aair.2014.6.3.252 · 3.08 Impact Factor
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    ABSTRACT: Children and adolescents with chronic diseases are commonly affected by a variable degree of growth failure, leading to an impaired final height. Of note, the peculiar onset during childhood and adolescence of some chronic diseases, such as type 1 diabetes, juvenile idiopathic arthritis, and asthma, underlines the relevant role of healthcare planners and providers in detecting and preventing growth abnormalities in these high risk populations. In this review article, the most relevant common and disease-specific mechanisms by which these major chronic diseases affect growth in youth are analyzed. In addition, the available and potential targeting strategies to restore the physiological, hormonal, and inflammatory pattern are described.
    International Journal of Endocrinology 02/2014; 2014:265954. DOI:10.1155/2014/265954 · 1.52 Impact Factor
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    ABSTRACT: Low and high birth weight have been linked to increased susceptibility to cardiovascular and metabolic alterations. However, the natural history of cardio-metabolic disturbances in children born small (SGA) and large (LGA) for gestational age is still unclear and no reliable biomarker of cardiovascular risk has definitively been identified in these subjects. Interestingly asymmetric dimethylarginine (ADMA), antagonist of nitric oxide (NO) production, has been recognized as novel cardio-vascular marker able to identify subjects at higher risk of health disturbances. Despite the well-described role of ADMA as predictor of degenerative disease in adults, its potential application in pediatrics, and specifically in SGA and LGA children, has not been explored as only few data in preterm infants and SGA newborns are available. Therefore, we investigated potential alterations in circulating ADMA and NO levels in SGA and LGA children compared with those born appropriate (AGA) for gestational age. Of note, ADMA was significantly higher in SGA and LGA children than AGA peers. Intriguingly, SGA and LGA categories as well as IR were independently related to ADMA. Our observations lead to the intriguing hypothesis that ADMA could be involved in the development of cardio-metabolic alterations in SGA and LGA children already during the prepubertal age.
    Antioxidants & Redox Signaling 12/2013; DOI:10.1089/ars.2013.5787 · 8.20 Impact Factor
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    ABSTRACT: To investigate whether there is an association of the tryglyceride-to-high density lipoprotein (TG/HDL-C) ratio with cardiovascular risk factors and early signs of vascular damage in obese prepubertal children. In 50 obese (27 boys, 7.8±1.4years) and 37 normal weight (20 boys; 7.3±1.5 years) prepubertal children, anthropometric measurements, oxidative stress markers (urinary prostaglandin F2α [PGF-2], soluble receptor for advanced glycation [sRAGE]) and insulin sensitivity (HOMA-IR and WBISI) were evaluated. Lipids profile was assessed and the TG/HDL-C ratio was calculated. In addition, high-resolution ultrasound was performed to assess carotid intima-media thickness (cIMT). Obese children showed significantly higher values of the TG/HDL-C ratio (1.9±1.1 vs. 1.2±0.6, p=0.004, p=0.004) compared to controls. After dividing the population in tertiles of the TG/HDL-C ratio (<1.04, 1.04-1.67, >1.67), cIMT (p=0.0003) and HOMA-IR (p=0.0001) progressively increased from the lower to the upper tertile, whereas WBISI (p=0.0003) and sRAGE (p=0.05) progressively decreased. In a regression model, the TG/HDL ratio was significantly and positively associated with cIMT (r= 0.493; p= 0.0005). A cutoff point for TG/HDL-C ratio of 1.12 had a 81% sensitivity and 49% specificity in the identification of children with values of cIMT in the upper quartile (AUC-ROC=0.633±0.065, p=0.045). This study confirms the realiability of the TG/HDL-C ratio as a useful marker of cardiovascular risk. Interestingly, our results underline that the TG/HDL-C ratio is directly related with early signs of vascular damage already in prepubertal children.
    European Journal of Endocrinology 10/2013; DOI:10.1530/EJE-13-0452 · 3.69 Impact Factor
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    ABSTRACT: Background and aimsParalleling the rise of pediatric obesity, the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) is increasing among youths. In this study we asked whether the co-occurrence of risk alleles in or near 5 genes modulating insulin secretion (TCF7L2 rs7903146, IGF2BP2 rs4402960, CDKAL1 rs7754840, HHEX rs1111875, and HNF1A rs1169288) is associated with a higher risk of IGT/ T2D in obese children and adolescents.Methods We studied 714 obese subjects (290 boys and 424 girls; mean age 13.6±3.1 years; mean z-score BMI 2.2±0.4), evaluated the insulin secretion by using the oral minimal model and, in a subgroup of 37 subjects, the hyperglycemic clamp. Also, 203 were followed-up for a mean of 2.1 years.ResultsWe observed that the increase of risk alleles was associated with a progressive worsening of insulin secretion (P<.001) mainly due to an impairment of the dynamic phase of insulin secretion (p=0.004). The higher was the number of the risk alleles the higher was the chance of progression from NGT to IGT/T2D (p=0.022), also for those who were IGT at baseline, a higher risk score was associated with a lower odds to revert to NGT (p=0.026).Conclusion Obese children and adolescents developing IGT/T2D have a higher genetic predisposition than those who do not show these diseases and this predisposition is mainly related to gene variants modulating the early phase of insulin secretion. Although these data are very interesting, they need to be replicated in other cohorts.
    Diabetes care 09/2013; 37(2). DOI:10.2337/dc13-1458 · 7.74 Impact Factor
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    ABSTRACT: In this study we sought to investigate the putative association of the oxidized metabolites derived from linoleic acid (OXFAs) with pediatric non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We studied 80 obese adolescents (age 13.3 ± 3.31 years; BMI 33.0± 6.79 Kg/m2), who underwent an oral glucose tolerance test (OGTT), a MRI to measure hepatic fat content, the measurement of OXFAs and CK-18, a robust biomarker of liver injury. Here we show that only in subjects with hepatic steatosis OXFAs are associated with CK-18 and that this association is modulated by the PNPLA3 rs738409 variant. We also show that most of the OXFAs are associated with a lower insulin secretion, and that adolescents with T2D have higher levels of OXFAs than subjects with impaired or normal glucose tolerance. These observations lead to the hypothesis that the OXFAs may be the pathogenic link between liver injury and T2D, and that novel therapeutic opportunities targeting OXFAs are possible in adolescents with early onset NAFLD and T2D.
    Antioxidants & Redox Signaling 07/2013; DOI:10.1089/ars.2013.5466 · 8.20 Impact Factor
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    ABSTRACT: The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children. We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05). The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 06/2013; DOI:10.1016/j.numecd.2013.04.005 · 3.52 Impact Factor
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    ABSTRACT: Objective Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF%<5.5 % and HFF%≥5.5 %, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis and insulin sensitivity.MethodsA total of 217 lean and obese adolescents with both low and high HFF% (Lean=31; Obese low HFF%=107; and obese high HFF%=79) underwent an Oral Glucose Tolerance Test (OGTT), a fast gradient Magnetic Resonance Imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels (CK18) were measured as biomarker of liver apoptosis. A subset of adolescents underwent a two-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N=14), to assess insulin sensitivity and steatohepatitis, respectively.ResultsCompared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (p<0.001). FGF-21 significantly correlated with adiposity indexes (P<0.001), Visceral Fat (r(2)=0.240, P<0.001), hepatic fat content (r(2)=0.278, P<0.001), CK18 (r(2)=0.217, P<0.001) and Alanine Aminotransferase (r(2)=0.164, P<0.001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the non-alcoholic fatty liver disease activity (NAS) score (r(2)=0.27, P=0.04). Stepwise regression analysis indicated that these relationships are independent of Body Mass Index, visceral fat and insulin sensitivity. An inverse correlation was documented with insulin, hepatic and adipose resistance indexes which disappeared after adjusting for hepatic fat content.Conclusions Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.
    The Journal of Clinical Endocrinology and Metabolism 04/2013; 98(7). DOI:10.1210/jc.2013-1250 · 6.31 Impact Factor
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    ABSTRACT: Abstract In obese adults with non alcoholic fatty liver disease (NAFLD), treatment with vitamin E has resulted in an improvement in liver histology, whereas variable and limited results are available in children. Our aim was to assess whether lifestyle combined with supplementation with Vitamin E might reduce oxidative stress and improve cardio-metabolic status in obese children with NAFLD. 24 obese prepubertal children (16M) followed a 6-month lifestyle intervention combined with vitamin E supplementation (600 mg/day) and compared with 21 age and sex-matched obese peers who underwent lifestyle intervention only. At baseline and after 6-month urinary prostaglandin F2α (PGF-2α); endogenous secretory receptor for advanced glycation end products (esRAGE), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferases (ALT), lipid profile, glucose and insulin were assessed. The two groups were comparable for age (8.3±1.6 vs 8.4±1.3 yr), sex and BMI SDS (2.16±0.29 vs 2.13±0.28). At the beginning of the study, PGF2-α, esRAGE and hsCRP, ALT, lipid profile and HOMA-IR levels were similar between the two groups (all p>0.05). After 6-month treatment, levels of PGF2-α (p<0.001) significantly decreased and esRAGE significantly increased (p<0.001) in children treated with vitamin E. A significant reduction was also found in ALT (p=0.001), lipid profile and HOMA-IR (p<0.001). In contrast, no significant change in any of these markers was detected in the lifestyle only group. In conclusion, vitamin E supplementation was associated with a significant reduction in oxidative stress and improved cardio-metabolic alterations. These data suggest that Vitamin E supplementation could represent a valuable treatment in obese children affected by NAFLD.
    Free Radical Research 12/2012; DOI:10.3109/10715762.2012.755262 · 3.28 Impact Factor
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    ABSTRACT: Insulin resistance associated with altered fat partitioning in liver and adipose tissues is a prediabetic condition in obese adolescents. We investigated interactions between glucose tolerance, insulin sensitivity, and the expression of lipogenic genes in abdominal subcutaneous adipose and liver tissue in 53 obese adolescents. Based on their 2-h glucose tests they were stratified in the following groups: group 1, 2-h glucose level <120 mg/dL; group 2, 2-h glucose level between 120 and 140 mg/dL; and group 3, 2-h glucose level >140 mg/dL. Liver and adipose tissue insulin sensitivity were greater in group 1 than in group 2 and group 3, and muscle insulin sensitivity progressively decreased from group 1 to group 3. The expression of the carbohydrate-responsive element-binding protein (ChREBP) was decreased in adipose tissue but increased in the liver (eight subjects) in adolescents with impaired glucose tolerance or type 2 diabetes. The expression of adipose ChREBPα and ChREBPβ was inversely related to 2-h glucose level and positively correlated to insulin sensitivity. Improvement of glucose tolerance in four subjects was associated with an increase of ChREBP/GLUT4 expression in the adipose tissue. In conclusion, early in the development of prediabetes/type 2 diabetes in youth, ChREBPβ expression in adipose tissue predicts insulin resistance and, therefore, might play a role in the regulation of glucose tolerance.
    Diabetes 12/2012; DOI:10.2337/db12-0889 · 7.90 Impact Factor
  • Cosimo Giannini, Sonia Caprio
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    ABSTRACT: The epidemic of childhood obesity has led to a remarkable increase in the prevalence of type 2 diabetes (T2D) among youth worldwide. The decreasing age at onset of T2D has alarming public health implications. In particular, the longer duration of the disease, as well as the faster onset and progression of T2D related complications, will present a considerable burden for young adults and a strain on public health. Therefore, it is important to understand the pathophysiology of early phases of disruption of glucose tolerance and identify those critical points in which diabetes may be prevented. β-Cell dysfunction has been shown to represent one of the key pathogenetic defects underlying the progression to diabetes in obese youth. In the present review, we describe longitudinal and cross-sectional studies of changes in insulin sensitivity and secretion across the spectrum of glucose tolerance in obese adolescents. Further, the role of ectopic fat accumulation is discussed in relation to its association with both β-cell dysfunction and insulin resistance.
    Current Diabetes Reports 11/2012; DOI:10.1007/s11892-012-0347-7 · 3.38 Impact Factor
  • C Giannini, S Caprio
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    ABSTRACT: Concurrent with the epidemic of childhood obesity, an unprecedented increase in the prevalence of several adiposity-related complications in this age group has emerged. In particular, type 2 diabetes (T2D), once considered an illness restricted to adulthood, is progressively affecting more and more adolescents, and represents now roughly 20-45% of new-onset cases in this age group. To unravel the pathogenesis of diabetes development during adolescence, many studies have focused on defining early defects in both insulin sensitivity and secretion that might be implicated in the natural history of the disease. Although a lot still need to be clarified, studies have shown that the progression from normal glucose tolerance to T2D involves intermediate stages of impaired fasting glucose and/or impaired glucose tolerance, also known as prediabetes. Insulin resistance and β-cell dysfunction represent the two major key pathogenetic defects underlying the progression to diabetes in obese youth. In this review, we have sought to mainly describe the role of β-cell function in relation to the ambient insulin resistance in the development of T2D in obese adolescents.
    Diabetes Obesity and Metabolism 10/2012; 14 Suppl 3:40-5. DOI:10.1111/j.1463-1326.2012.01643.x · 5.18 Impact Factor
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    ABSTRACT: OBJECTIVE We used fast-gradient magnetic resonance imaging (MRI) to determine the longitudinal associations between the hepatic fat content (HFF), glucose homeostasis, and a biomarker of hepatocellular apoptosis in obese youth.RESEARCH DESIGN AND METHODS Baseline and longitudinal liver and abdominal MRI were performed with an oral glucose tolerance test in 76 obese youth followed for an average of 1.9 years. Cytokeratin-18 (CK-18) was measured at baseline and follow-up as a biomarker of hepatic apoptosis. The relationship between baseline HFF and metabolic parameters and circulating levels of CK-18 at follow-up were assessed using a bivariate correlation.RESULTSAt baseline, 38% had hepatic steatosis based on %HFF ≥5.5% with alterations in indices of insulin sensitivity and secretion. At follow-up, BMI increased in both groups and baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group. Baseline HFF correlated with 2-h glucose (r = 0.38, P = 0.001), whole-body insulin sensitivity (r = -0.405, P = 0.001), adiponectin (r = -0.44, P < 0.001), CK-18 levels, (r = 0.63, P < 0.001), and disposition index (r = -0.272, P = 0.021) at follow-up. In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.CONCLUSIONS In obese youth, the phenotype of MRI-measured hepatic steatosis is persistent. Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.
    Diabetes care 08/2012; 36(1). DOI:10.2337/dc12-0277 · 7.74 Impact Factor
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    ABSTRACT: Background. Insulin resistance (IR), a link of paramount importance between obesity and cardiovascular/metabolic complications, seems to be implicated in weight changes. Objective. To determine whether IR could influence weight status during a 1-year intervention program in obese prepubertal children. Methods. Forty-four children with IR (IR group) and 42 children without IR (NIR group) were enrolled. Body mass index standard deviation score (BMI-SDS), waist circumference (WC), and homeostasis model assessment (HOMA-IR) were evaluated. Results. NIR children showed a significant reduction of BMI-SDS and WC at final assessment (p = 0.009 and p = 0.001, respectively), whereas IR children presented unchanged values. HOMA-IR decreased after intervention in the NIR group (p = 0.0008), but was exacerbated in IR children (p = 0.004). A positive and significant association between HOMA-IR at baseline and BMI at follow-up was found (B ± SE = 0.87 ± 0.24, p = 0.001). HOMA-IR at baseline was also significantly associated with WC at follow-up (B ± SE = 2.12 ± 0.69, p = 0.003). Conclusions. IR seems to influence adiposity changes in obese prepubertal children. Further longitudinal studies are needed to verify the relationship between IR and weight loss during childhood.
    Endocrine Research 08/2012; DOI:10.3109/07435800.2012.713424 · 1.41 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate the presence of possible early atherosclerotic changes in a group of prepubertal children with juvenile idiopathic arthritis (JIA) and to establish the potential beneficial effects of 1-year treatment. MATERIALS AND METHODS: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), proinflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α), lipid profile and oxidant-antioxidant status (urinary isoprostanes [PGF-2α]) were assessed in 38 JIA children (12M/26F, mean age 7.05 ± 2.39 years) and compared with 40 controls (18M/22F, mean age 6.34 ± 2.25 years). Carotid intima-media wall thickness (cIMT) was obtained and blood pressure was measured. All parameters were reassessed in JIA children after 1 year of therapy. RESULTS: At baseline JIA children presented compared to controls higher levels of inflammatory markers, proinflammatory cytokines, total cholesterol, LDL cholesterol, and PGF-2α (all p ≤ 0.01). Furthermore, blood pressure and cIMT were significantly increased (both p ≤ 0.01). After a 1-year treatment with non-steroid anti-inflammatory (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), a significant reduction of all parameters was detected (all p ≤ 0.01). This was associated with a significant reduction in blood pressure and cIMT (both p ≤ 0.01). Within the JIA group, patients requiring etanercept presented worse laboratory values and cIMT measurements at baseline. Nevertheless, the same improvement of all parameters was obtained after a 1-year treatment. In stepwise multiple regression, LDL cholesterol and IL-1β were mainly related to cIMT. CONCLUSION: Chronic and systemic inflammation seems to lead to early atherosclerotic abnormalities even in pre-pubertal JIA children. Substantial improvement can be obtained with 1-year of appropriate therapy.
    Clinical Research in Cardiology 08/2012; 102(1). DOI:10.1007/s00392-012-0496-3 · 4.17 Impact Factor
  • The Journal of pediatrics 05/2012; 161(4):769-769.e1. DOI:10.1016/j.jpeds.2012.04.034 · 4.02 Impact Factor
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    ABSTRACT: To assess potential alterations in soluble and endogenous secretory receptors for advanced glycation end products (sRAGE and esRAGE) in normal-weight (NW) and obese (Ob) children born small (SGA) and large (LGA) compared with appropriate for gestational age (AGA) subjects and to explore if birth weight (BW), insulin resistance (IR), and obesity represent independent risk factors. We categorized 130 prepubertal children into six groups according to BW and obesity and evaluated sRAGE, esRAGE, and homeostasis model assessment of IR. sRAGE and esRAGE were lower in Ob SGA and LGA children than Ob AGA subjects (all P < 0.05), and in NW SGA and LGA children than NW AGA subjects (all P < 0.05). Interestingly, BW and IR were significantly and independently related to RAGE. sRAGE and esRAGE are decreased in SGA and LGA children, and BW and IR seem to play an important role in the reduction of RAGE.
    Diabetes care 04/2012; 35(6):1361-3. DOI:10.2337/dc11-2302 · 7.74 Impact Factor
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    ABSTRACT: There is a worsening high prevalence of global obesity. Special attention has been paid to the gut-endocrine system, represented by the regulators of appetite. In particular, it has been suggested that ghrelin ("hunger" peptide), and obestatin and glucagon-like peptide-1 (GLP-1) ("satiety" peptides) could play important roles in the pathogenesis of obesity. The aims of this study were to compare fasting plasma ghrelin, obestatin, and GLP-1 levels between obese and nonobese prepubertal children, and to assess their relations with fatness indexes and insulin resistance (IR). Fifty-two prepubertal obese children and 22 controls were enrolled. Fasting levels of gastrointestinal hormones (ghrelin, obestatin, and GLP-1), glucose, and insulin were evaluated. IR was assessed using the homeostasis model assessment of IR (HOMA-IR) index. Analysis was performed by Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation. Obese prepubertal children and normal-weight controls had similar age distribution. Obese children were more insulin resistant when compared to controls (HOMA-IR: p < 0.01 ). GLP-1 levels were significantly lower in obese children than in controls (p < 0.01). Obestatin was significantly higher in obese than normal-weight children (p < 0.01), while ghrelin was not different. There was a negative correlation between GLP-1 and standard deviation score-body mass index (r = -0.36, p = 0.009) and between GLP-1 and waist circumference (r = -0.45, p = 0.001), while no association was observed with HOMA-IR. GLP-1 levels have been shown to be correlated with adiposity indexes, but not with HOMA-IR, suggesting that this hormone could play an important role in the early development of obesity.
    Journal of pediatric endocrinology & metabolism: JPEM 04/2012; 25(3-4):255-60. DOI:10.1515/jpem-2011-0478 · 0.71 Impact Factor

Publication Stats

667 Citations
239.43 Total Impact Points


  • 2014
    • Yale University
      • Department of Pediatrics
      New Haven, Connecticut, United States
  • 2005–2014
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • • Pediatric Clinic
      • • Clinical Research Center CRC
      Chieta, Abruzzo, Italy
  • 2013
    • University of New Haven
      New Haven, Connecticut, United States
  • 2012
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States