Cosimo Giannini

Yale University, New Haven, Connecticut, United States

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Publications (65)268.52 Total impact

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    ABSTRACT: The innate immune cell sensor, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome controls activation of caspase-1 and release of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is implicated in adipose tissue inflammation and pathogenesis of insulin resistance. Herein we tested the hypothesis that adipose tissue inflammation and NLRP3-inflammasome are linked to downregulation of subcutaneous adipose tissue (SAT) adipogenesis/lipogenesis in obese adolescents with altered abdominal fat partitioning.We performed abdominal subcutaneous adipose tissue biopsies on 58 obese adolescents and grouped them by MRI derived visceral to subcutaneous ratio (VAT/VAT+SAT) (cut-off 0.11). Adolescents with the high VAT/VAT+SAT showed higher SAT macrophage infiltration and higher expression of the NLRP3-inflammasome related genes, i.e. TLR4, NLRP3, IL1B and CASP1. The increase in inflammation markers was paralleled by a decrease in genes related to insulin sensitivity (ADIPOQ, GLUT4, PPARG2, SIRT1) and lipogenesis (SREBP1c, ACC, LPL, FASN). Furthermore, SAT ceramide concentrations correlated with the expression of CASP1 and IL1Β.Infiltration of macrophages and upregulation of the NLRP3-inflammasome together with the associated high ceramide content in plasma and SAT of obese adolescents with a high VAT/VAT+SAT ratio may contribute to the limited expansion of the subcutaneous abdominal adipose depot and the development of insulin resistance.
    No preview · Article · Dec 2015 · Diabetes
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    ABSTRACT: Human plasma is a biofluid that is high in information content, making it an excellent candidate for metabolomic studies. (1)H NMR has been a popular technique to detect several dozen metabolites in blood plasma. In order for (1)H NMR to become an automated, high-throughput method, challenges related to (1) the large signal from lipoproteins and (2) spectral overlap between different metabolites have to be addressed. Here diffusion-weighted (1)H NMR is used to separate lipoprotein and metabolite signals based on their large difference in translational diffusion. The metabolite (1)H NMR spectrum is then quantified through spectral fitting utilizing full prior knowledge on the metabolite spectral signatures. Extension of the scan time by 3 minutes or 15% per sample allowed the acquisition of a (1)H NMR spectrum with high diffusion weighting. The metabolite (1)H NMR spectra could reliably be modeled with 28 metabolites. Excellent correlation was found between results obtained with diffusion NMR and ultrafiltration. The combination of minimal sample preparation together with minimal user interaction during processing and quantification provides a metabolomics technique for automated, quantitative (1)H NMR of human plasma.
    No preview · Article · Dec 2015 · Metabolomics
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    ABSTRACT: Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 μmol/l, p < 0.001). Values of 24-h systolic and diastolic BP SDS (0.86 ± 0.79 vs 0.42 ± 0.83, p = 0.001; -0.45 ± 0.82 vs 0.08 ± 0.51, p = 0.001) were significantly increased at visit_2 compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (p < 0.05). Changes in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.
    No preview · Article · Jul 2015 · Journal of endocrinological investigation
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    ABSTRACT: Objective Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity.Methods Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes.ResultsBaseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose.Conclusions Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating.
    No preview · Article · Feb 2015 · Obesity
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    ABSTRACT: Impaired glucose effectiveness (GE) plays a role in the deterioration of glucose metabolism. Our aim was to validate a surrogate of GE derived from an oral glucose tolerance test (OGTT), and to assess the impact of degrees of obesity and of glucose tolerance on it. The OGTT-derived surrogate of GE (oGE) was validated in obese adolescents who underwent an OGTT and an intravenous glucose tolerance test (IVGTT). We then evaluated anthropometric determinants of the oGE and its impact on the dynamics of glucose tolerance in a cohort of children with varying degrees of obesity. The correlation of oGE and IVGTT-derived GE in 98 obese adolescents was r = 0.35 (P < 0.001) as a whole, and r = 0.51 (P < 0.001) in subjects with normal glucose tolerance. In a cohort of 1,418 children, the adjusted GE was associated with increasing obesity (P < 0.001 for each category of obesity). Quartiles of oGE and the oral disposition index were associated with 2-h glucose levels (P < 0.001 for both). Among 421 nondiabetic obese subjects (276 subjects with normal glucose tolerance/145 subjects with impaired glucose tolerance who repeated their OGTT after a mean time of 28 ± 16 months), oGE changes were tightly associated with weight (r = 0.85, P < 0.001) and waist circumference changes (r = 0.67, P < 0.001). Baseline oGE and changes in oGE over time emerged as significant predictors of the change in 2-h glucose levels (standardized Β = -0.76 and Β = -0.98 respectively, P < 0.001 for both). The oGE is associated with the degree of and changes in weight and waist circumference, and is an independent predictor of glucose tolerance dynamics. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    No preview · Article · Jan 2015 · Diabetes Care
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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
    Preview · Article · Aug 2014 · Diabetologia
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    ABSTRACT: Objective: 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. Research design and methods: Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Results: Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). Conclusions: This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D.
    Full-text · Article · Aug 2014 · Diabetes Care
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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.
    Full-text · Article · May 2014 · Allergy, asthma & immunology research
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    Cosimo Giannini · Angelika Mohn · Francesco Chiarelli
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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.
    Full-text · Article · Feb 2014 · International Journal of Endocrinology
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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.
    No preview · Article · Dec 2013 · Antioxidants & Redox Signaling
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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.
    Preview · Article · Oct 2013 · European Journal of Endocrinology
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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.
    Preview · Article · Sep 2013 · Diabetes care
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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.
    No preview · Article · Jul 2013 · Antioxidants & Redox Signaling
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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.
    No preview · Article · Jun 2013 · Nutrition, metabolism, and cardiovascular diseases: NMCD
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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.
    No preview · Article · Apr 2013 · The Journal of Clinical Endocrinology and Metabolism
  • Cosimo Giannini · Sonia Caprio
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    ABSTRACT: Type 2 diabetes (T2D), once considered an illness restricted to adults, is progressively affecting more and more adolescents as population rates of obesity increase. Estimates suggest that T2D represents 20–25% of new-onset cases in adolescents and that certain ethnic or racial groups are ­disproportionately affected. Its onset during adolescence represents a serious health burden as T2D shortens life expectancy and is associated with serious medical complications. Thus, effective treatments are urgently needed for youths who face the possibility of experiencing these complications at an earlier age than their adult counterpart. Therefore, the complete characterization of the pathophysiology of the disease represents a key element for assessing its risks and determining factors.
    No preview · Chapter · Jan 2013
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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.
    No preview · Article · Dec 2012 · Free Radical Research
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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.
    Preview · Article · Dec 2012 · Diabetes
  • 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.
    No preview · Article · Nov 2012 · Current Diabetes Reports
  • 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.
    No preview · Article · Oct 2012 · Diabetes Obesity and Metabolism

Publication Stats

942 Citations
268.52 Total Impact Points

Institutions

  • 2011-2015
    • Yale University
      • Department of Pediatrics
      New Haven, Connecticut, United States
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2004-2015
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • • Pediatric Clinic
      • • Clinical Research Center CRC
      Chieta, Abruzzo, Italy
  • 2012
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States