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Background and aim: To compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines. Methods and results: This cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP >= 90th to = 120/80 to

Cardiovascular disease is the leading cause of morbidity and mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk is higher in women with diabetes than in men. With this study, we wanted to determine whether female children and adolescents with T1DM are more prone to cardiovascular risk factors (CVRFs) and an atherogenic diet than boys.For this cross-sectional study, anthropometric, clinical, biochemical, and dietary intake data of 314 children with diabetes (3-18 years; 178 boys) were analysed according to age and sex. Linear and binary logistic regression was performed to test independent associations between sex, dietary intake, and CVRFs. Low-density lipoprotein -cholesterol (LDL-c), triglyceride (TG), fibre, monounsaturated fatty acid levels (all p 0.01), and lipid (p = 0.022) intake were higher in the girls than in the boys. Multiple regression analysis showed that LDL was associated with sex, glycated haemoglobin (HbA1c), and lipid intake percentage (R (Kannel, 1979) [2] = 0.130; p = 0.0004) independent of age, pubertal stage, body mass index (BMI), duration of diabetes, energy, and fibre intake. Logistic regression analysis showed that high LDL-c levels were present more often in girls [odds ratio, OR; confidence interval, CI = 2.569 (1.178-5.604); p = 0.018] who had a higher dietary lipid intake percentage [OR (CI) = 1.089 (1.011-1.173); p = 0.025].Girls with diabetes have higher LDL-c levels associated with higher dietary lipid intake. Our findings suggest that young people with diabetes, especially girls, may benefit from early dietary interventions to reduce their cardiovascular risk.

Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D).Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid–femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage.Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT.Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.

Aims We assessed whether oxidative stress (OS) is increased in children/adolescents with type 1 diabetes (T1D) compared to healthy peers. Moreover, we searched for OS predictors in the T1D population. Methods We compared the concentration of serum derivatives of reactive oxygen metabolites (d-ROMs) in 412 children/adolescents with T1D (3.6–23.5 years old) to that of 138 healthy children/adolescents (1.2–19.2 years old) by ANOVA adjusted for age, gender, and BMI z-score (z-BMI). Applying a general linear model, in a subgroup of 331 patients using continuous glucose monitoring, we searched for predictors of d-ROMs among 3-day, 2-week, and 4-week metrics of glucose control and variability, such as mean blood glucose, percent time in range (70–180 mg/dl,TIR70-180), coefficient of variation, and others, as well as among conventional cardiovascular risk factors like current and average HbA1c, z-BMI, blood pressure percentiles, and lipid concentrations recorded retrospectively over the entire follow-up period. Results D-ROMs levels were significantly higher in children/adolescents with T1D compared to controls [371.9 (64.2) versus 324.9 (46.3), p Conclusions OS is increased in youth with T1D and only partially predicted by gender, age, glucose control, and anthropometry. Other potential determinants of OS in this population should be targeted in future studies.

BackgroundNonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD.AimsWe examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors.MethodsWe recruited a cohort of 514 obese children and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system.ResultsThe overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2 rs58542926 (OR = 4.13, p = 0.002), GCKR rs1260326 (OR = 1.53, p = 0.003), PNPLA3 rs738409 (OR = 1.58, p = 0.004) and ELOVL2 rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75–0.88] vs. 0.77 [0.70–0.84] without SNPs; p = 0.047).ConclusionsNAFLD was strongly associated with three genetic variants, TM6SF2 rs58542926, PNPLA3 rs738409 and GCKR rs1260326, and more slightly with ELOVL2 rs2236212, in obese children and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.

Objective Vitamin D may potentially play a central role in glucose homeostasis and β-cell function (BCF), although studies are not consistent. Aim of our study was to test the hypotheses of a direct relationship between vitamin D, insulin sensitivity (IS) and BCF in overweight and obese non-diabetic children. Design and methods Cross-sectional study carried out at the Childhood Obesity Outpatient Clinic, University Hospital of Verona. One hundred twenty-two Caucasian overweight and obese children (age: 12.8 ± 0.2 years) were enrolled. Exclusion criteria: genetic or endocrine causes of obesity, chronic diseases or therapies. Patients underwent oral glucose tolerance test. HOMA-IR, Matsuda index and insulinogenic index were calculated. BCF was reconstructed by mathematical modeling and described by Derivative and Proportional Control. Total 25-hydroxyvitamin D and vitamin D-binding protein (VDBP) were measured. Two SNPs (rs4588 and rs7041) in the VDBP gene were studied, and bioavailable vitamin D (BVD) was calculated. Results Hypovitaminosis D was documented in 90% of patients. Forty-seven subjects were homozygous for both SNPs. Total vitamin D was positively correlated with Matsuda index (P = 0.002), VDBP (P = 0.045), and negatively with BMI SDS (P = 0.043), HOMA-IR (P = 0.008), HOMA-B (P = 0.001), IGI (P = 0.007), derivative control (P = 0.036) and proportional control (P = 0.018). Total vitamin D, adjusted for age, gender, BMI SDS, puberty and seasonality of vitamin D measurement, was a predictor of Matsuda index, HOMA-IR, HOMA-B, IGI, proportional control (all P P P = 0.041). Conclusions Hypovitaminosis D negatively influences BCF and IS, suggesting that vitamin D levels might be implicated in glucose metabolism impairment in overweight and obese individuals.

To assess whether combining glucose shape and 2-h glucose concentration during an oral glucose tolerance test (OGTT) may help identifying normal glucose tolerant obese children/adolescents with an impaired glucose tolerant (IGT)-like metabolic profile in term of insulin sensitivity (Matsuda index) and β-cell function (disposition index: DI).In total, 654 non-diabetic obese children/adolescents underwent a 2 h OGTT. The whole population was classified according to 2-hour plasma glucose ( 100, 100-119, 120-139, 140-200 mg/dL) and glucose shape (monophasic or biphasic). Monophasic morphology was characterized by an increase in OGTT glucose concentration followed by a decline of at least 4.5 mg/dL, a biphasic response was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 4.5 mg/dL. A subset of 69 participants had also a prolonged OGTT to estimate β-cell function in "biphasic" versus "monophasic" patients.Matsuda index and DI decreased across 2-h glucose categories (both p 0.001) and were lower in monophasic compared with biphasic children, independently of 2-h glucose category (both p 0.001, both p for glucose category×shape interaction 0.05). Normal glucose tolerant children with 2-h glucose of 120-139 mg/dl and monophasic glucose shape did not differ from IGT children, as regards Matsuda index and DI (both p 0.05). Among children undergoing a prolonged OGTT, those with a monophasic glucose shape had worse β-cell function, modeled as proportional control, than those with a biphasic shape (p = 0.031).A monophasic OGTT glucose shape is associated with unfavorable glucose metabolism independently of 2-h glucose concentration. Children combining monophasic shape and normal-high 2-h glucose have an IGT-like glucose metabolism.

Background and aim: The relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB). Methods and results: A cross-sectional study was performed in 2248 youths with OW/OB (age 5–17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025–0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005–0.0001). Conclusions: In youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post–challenge condition rather than in fasting state.

Background: Several studies identified genetic variants in FADS and ELOVL2 genes associated with obesity-related conditions, such as alterations in blood lipid parameters and insulin homeostasis. The aim of this cross-sectional study was to determine whether FADS and ELOVL2 genetic variants were associated with obesity and adiposity, besides dyslipidaemia and insulin resistance, in a large sample of obese children and adolescents. Materials and methods: One thousand six hundred and forty-nine obese children underwent physical examination, anthropometry, fasting blood tests measuring plasma glucose, lipid and liver profile. Two genetic variants were genotyped: rs2236212 in ELOVL2 gene and rs1535 in FADS2, for the gene cluster FADS. In a subgroup of obese children (n = 105), erythrocyte fatty acid composition was measured. Generalized linear models were used to assess association between genotypes and variables. Results: A positive association between zBMI and the minor allele of rs2236212 (p = 0.028), the major allele of rs1535 (p = 0.046) and the genetic score (p = 0.008), created by summing up both risk alleles, were found. The estimation of enzymatic activity revealed that minor alleles were associated significantly with a reduction of the enzymatic activity of elongase and desaturase (p = 0.048 and p = 0.0001, respectively). Discussion and conclusions: Common variants in the FADS2 and ELOVL2 genes were associated with BMI in a large population of obese Italian children. These SNPs were associated with alterations in LC-PUFAs homeostasis, not accompanied by modifications of plasma lipids or HOMA-IR. These findings provide additional support to the genetics accounting for BMI interindividual variability and the molecular basis of obesity.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Objective To test the hypothesis that lipid intake is associated with triglycerides to HDL-cholesterol ratio (TG/HDL-cholesterol), a predictor of the development of cardiovascular disease, in obese children and adolescents, independently from the level of overweight, insulin resistance, blood pressure, and non-alcoholic fatty liver disease (NAFLD). Study design One hundred and eighty non-diabetic obese children/adolescents (age range 6-16 years) were enrolled. Diet (3-day weighed dietary record), physical and biochemical parameters and liver ultrasonography were measured. The impact of lipid intake on TG/HDL-cholesterol ratio >2.2 was measured by regression models, adjusting for covariates (age, gender, height, weight, systolic and diastolic blood pressure, NAFLD positivity, HOMA-IR, and total energy intake). Results Independently from covariates, children consuming a diet with a fat content higher than 35% of total energy had a significantly higher chance [OR = 3.333 (95% CI: 1.113-9.979), P = 0.031] to have a TG/HDL-cholesterol >2.2 than children consuming less than 35% of fat. Moreover, if saturated fatty acids (SFA) intake was higher than 13% of total energy, children had a significantly higher chance [OR = 4.804 (95% CI: 1.312-17.593), P = 0.018] to have a TG/HDL-cholesterol >2.2 than children consuming less than 13% of SFA in their diet. Conclusions High fat intake, especially SFA intake, is associated with TG/HDL-cholesterol levels of obese children and adolescents, independently from other cardiovascular risk co-factors. Further intervention studies will contribute to clarify the potential role of changes in the composition and amount of fat in the diet of obese children and adolescents, on their cardiovascular risk factors.

Background and aim The association between non-alcoholic fatty liver (NAFL) and the variant rs641738 within the membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene is currently uncertain, especially in the paediatric population. We examined whether there is an association between this genetic variant and NAFL in a large multicentre, hospital-based cohort of Italian overweight/obese children. Methods and results We studied 1760 overweight or obese children [mean age (SD): 11.1(2.9) years, z-body mass index (zBMI) 3.2(0.9)], who underwent ultrasonography for the diagnosis of NAFL. A subgroup of these children (n = 182) also underwent liver biopsy. Genotyping of the MBOAT7 rs641738 polymorphism was performed by TaqMan-Based RT-PCR system in each subject. Overall, 1131 (64.3%) children had ultrasound-detected NAFL; 528 (30%) had rs641738 CC genotype, 849 (48.2%) had rs641738 CT genotype, and 383 (21.8%) had rs641738 TT genotype, respectively. In the whole cohort, the interaction of MBOAT7 genotypes with zBMI was not associated with NAFL after adjustment for age, sex, serum triglycerides, serum alanine aminotransferase levels and patatin-like phospholipase domain-containing protein-3 (PNPLA3) genotype (adjusted-odds ratio 1.02 [95% CI 0.98–1.06]). Similarly, no association was found between MBOAT7 genotypes and NAFL after stratification by obesity status. MBOAT7 genotypes were not associated with the presence of non-alcoholic steatohepatitis or the stage of liver fibrosis in a subgroup of 182 children with biopsy-proven NAFLD. Conclusions The results of this study did not show any significant contribution of MBOAT7 rs641738 polymorphism to the risk of having either NAFL on ultrasonography or NASH on histology in a large hospital-based cohort of Italian overweight/obese children.

Background and aims: Birth weight (BW) has been associated with the risk of obesity and metabolic derangements in children and adults. The aims of this study were: i. to evaluate the distribution of BW in a sample of overweight and obese children and adolescents compared with the general reference population; ii. to explore the relationship between the BW and insulin resistance and other cardiometabolic derangements in a population of children and adolescents with overweight and obesity. Methods and results: 710 overweight and obese children and adolescents were recruited and categorized into small (SGA), appropriate (AGA), and large (LGA) for gestational age, according to the BW percentile. Arterial blood pressure, lipid profile, glucose metabolism and hepatic steatosis were evaluated to assess cardiometabolic obesity-related derangements. The distribution of BW categories in our population was significantly different compared with the general population (SGA 6.9% vs. 8.6%, AGA 74.6% vs. 81.4%, LGA 18.5% vs. 10%; p < 0.0001). We found a higher frequency of prediabetes conditions (21.7% vs 8.9%, OR 2.97, 95% CI 1.38–6.38, p = 0.005) and borderline/high low-density lipoprotein cholesterol (31.8% vs 18.6%, OR 2.13, 95% CI 1.09–4.18, p = 0.033) in overweight and obese children born SGA compared to those born non-SGA, independently of age, sex, and BMI. Conclusions: BW is a risk factor of cardiometabolic derangements in a population of children and adolescents with overweight and obesity. Therefore, adequate obesity prevention strategies should be planned for children born SGA to minimize their risk to become obese and to reduce their short- and long-term cardiometabolic risks.

Background and aims Fatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D. Methods and results We recruited 154 adolescents with T1D (aged 17.3±2 years,82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r=-0.32,p=6.6*10-5) and directly with triglycerides (r=0.24, p=0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r=-0.26, p=0.002). We found some weak (r≤0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing. Conclusion In youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.

BACKGROUND Diet plays a key role in the treatment of type 1 diabetes (T1D). Dietary habits changed rapidly in the last decades and few data are available on recent dietary changes in children and adolescents with T1D. OBJECTIVE To test the hypothesis that diet composition changed in a 10-year period in children and adolescents with T1D. METHODS Two hundred and twenty-nine T1D subjects (M/F:121/108) aged 6 to 16 years were recruited: 114 (group A) enrolled in 2009, not using CGM and/or CSII, and 115 (group B) enrolled in 2019. Anthropometric biochemical (HbA1c, lipid profile), diet, and insulin therapy parameters were compared between the two groups. Multivariate logistic regression analysis was performed with HbA1c as dependent variable (HbA1c > 58 mmol/mol = 1) and nutritional variables and technology use as independent ones. RESULTS Energy intake of group A was not statistically different from that of group B. Group B had a significantly (P

Oxidative stress leading to endothelial dysfunction is a candidate driver of obesity-related hypertension. We aimed to assess whether the total anti-oxidant capacity (TAC) was associated with blood pressure in children/adolescents with obesity.One hundred and fifty-two children/adolescents with obesity (79 boys; age 11.9+/-2.5 years) underwent blood drawing for the assessment of TAC, lipids and HOMA-IR. Blood pressure was measured and classified according to the latest American Academy of Pediatrics Guidelines. Serum TAC was measured by a commercial kit (Sigma-Aldrich). The average TAC was 1.11+/-0.4 mMol/Trolox equivalents. Systolic blood pressure was predicted by TAC (B = -5.8, p = 0.003), z-BMI (B = 2.39, p = 0.008), height [cm] (B = 0.38, p 0.001) and diastolic blood pressure (B = 0.56, p 0.001). Diastolic blood pressure was predicted by age [years] (B = 0.58, p = 0.001), log-HOMA-IR (B = 3.0, p = 0.002), and systolic blood pressure (B = 0.26, p 0.001), but not by TAC. The pulse pressure was predicted only by TAC (B = - 6.6, p = 0.002), and height [cm] (B = 0.42, p 0.001). Overall "elevated blood pressure + hypertension" or hypertension alone were not associated with TAC. However, systolic "elevated blood pressure + hypertension" was associated with TAC (OR = 0.4 [0.1-0.9], p = 0.037), and z-BMI (OR = 2.1 [1.3-3.6], p = 0.004).The systemic anti-oxidant capacity is inversely associated with systolic blood pressure and pulse pressure in children and adolescents with obesity.

ContextNonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and predicts type 2 diabetes. Currently, it is uncertain whether NAFLD may directly cause IR or vice versa.ObjectiveTo test the hypothesis that NAFLD is causally related to IR.Design and MethodsWe performed a Mendelian randomization (MR) in 904 obese children/adolescents using an NAFLD-related genetic risk score (GRS) as an instrumental variable. We assessed NAFLD by ultrasonography and IR by homeostasis model assessment (HOMA-IR). We also interrogated the MAGIC Consortium dataset of 46 186 adults to assess the association between PNPLA3 rs738409 (ie, the most robust NAFLD-related polymorphism) and HOMA-IR, and we performed a 2-sample MR with 2 large datasets to test reverse causation (HOMA-IR increasing the risk of NAFLD).ResultsNonalcoholic fatty liver disease prevalence increased by 20% for every increase in the GRS (β-coefficient = 0.20, P < 0.001), and NAFLD was associated with ln-HOMA-IR (β-coefficient = 0.28, P < 0.001). Thus, the expected increase in ln-HOMA-IR for every increase in the GRS (expected β-coefficient) was 0.056 (0.28*0.20) in the case of complete NAFLD-HOMA-IR causal association, and 0.042 in the case of 75% causality. In our cohort, the GRS did not predict ln-HOMA-IR (β-coefficient = 0.007, P = 0.75). In the MAGIC cohort, the PNPLA3 rs738409 did not associate with ln-HOMA-IR. The 2-sample MR failed to show a causal association between ln-HOMA-IR and NAFLD.ConclusionsOur study shows that genetically-influenced NAFLD does not increase HOMA-IR, and genetically-influenced HOMA-IR does not increase the risk of NAFLD. Shared pathogenic pathways or NAFLD subtypes not “captured” by our MR design might underpin the association between NAFLD and HOMA-IR.

OBJECTIVE: To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS: Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as >= 75th percentile by sex in children and adolescents. RESULTS: The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS: High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.

In order to assess whether flavin-containing monooxygenase-3 (FMO3) might be involved in early cardiovascular risk, we assessed adiposity and traditional metabolic variables in children/adolescents grouped according to their genotypes in two FMO3 exonic polymorphisms, rs2266782 (E158K) and rs2266780 (E308G), which are in linkage disequilibrium and have been associated with decreased FMO3 activity. Among 776 children/adolescents (10.8 ± 2.2 years) recruited from the general population (452) and from our obesity outpatient clinic (324), the 68 carrying either the 158K-308G/158K-308E or the 158K-308G/158K-308G diplotype had lower mean z-BMI and prevalence of obesity compared to their 708 peers carrying any of the other diplotypes (0.39 vs 0.80, p = 0.01; OR = 0.39[0.17-0.87], p = 0.018, respectively), and to the sub-sample of 303 children carrying the major diplotype (158E-308E/158E-308E) (0.39 vs 0.87, p = 0.008; OR = 0.35[0.16-0.81], p = 0.014, respectively). They also had lower z-BMI-adjusted lnHOMA-IR compared to all the other children (0.75 vs 0.97, p = 0.001) and those carrying the major diplotype, (0.75 vs 0.98, p = 0.03), as well as lower z-BMI-adjusted iln-triglycerides compared to all the other children (3.98 vs 4.17, p = 0.037). These associations provide the first evidence that FMO3 may be involved in early body weight, insulin sensitivity, and lipid regulation in humans.

We evaluated the performance of a new simple formula (NSF) for the screening of hypertension by American Academy of Pediatrics Guidelines 2017 (AAPG2017) in children with overweight/obesity (OW/OB). The performance of the NSF and the modified blood pressure to height ratio (MBPHR3) thresholds against AAPG2017 was evaluated; both methods were also compared to assess the association with concentric left ventricular hypertrophy (cLVH). The study included 3259 OW/OB children (5-13 years). Two centers served as learning sample (LS) (n = 1428), four centers served as validation sample (VS) (n = 1831), and the echocardiographic evaluation was available in 409 children in VS. The NSF was [1.5 × systolic blood pressure (mmHg) + diastolic blood pressure (mmHg)] - [(26 × height (m)] - age (years). A cut-off of the NSF >= 193 mmHg showed sensitivity, specificity, positive, and negative predictive values of 0.92, 0.93, 0.83, and 0.97, respectively, versus the standard procedure. Against AAPG2017, the NSF showed higher specificity and positive predictive values than the MBPHR3 thresholds. Among hypertensive children defined by AAPG2017, NSF, or MBPHR3, the odds ratio (95%CI) for cLVH was respectively 1.73 (1.06-2.83), 1.69 (1.05-2.75), and 1.18 (0.75-1.85).Conclusions: The NSF shows a very high performance for the screening of OW/OB children at risk of hypertension and cLVH. What is Known: o The American Academy of Pediatrics released updated guidelines (AAPG 2017) to classify hypertension (HTN) in children. o The process needs categorization of height percentiles and comparison of blood pressure versus gender and age-adjusted values. What is New: o A user-friendly formula built on the AAPG 2017 was validated for the categorization of HTN in children with overweight/obesity. o The formula showed high performance in identifying children with HTN versus the standard procedure (sensitivity 0.92, specificity 0.93) and similar ability in identifying hypertensive children with concentric left ventricular hypertrophy versus the standard procedure (40% and 39% respectively).

Background An assessment of total daily energy intake is helpful in planning the overall treatment of children with type 1 diabetes (T1D). However, energy intake misreporting may hinder nutritional intervention. Aims To assess the plausibility of energy intake reporting and the potential role of gender, body mass index (BMI) z-score (z-BMI), disease duration and insulin requirement in energy intake misreporting in a sample of children and adolescents with T1D. Methods The study included 58 children and adolescents aged 8–16 yr with T1D. Anthropometry, blood pressure and glycated hemoglobin (HbA1c) were measured. Subjects were instructed to wear a SenseWear Pro Armband (SWA) for 3 consecutive days, including a weekend day and to fill out with their parents a weighed dietary record for the same days. Predicted energy expenditure (pEE) was calculated by age and gender specific equations, including gender, age, weight, height and physical activity level (assessed by SWA). The percent reported energy intake (rEI)/pEE ratio was used as an estimate of the plausibility of dietary reporting. Results Misreporting of food intake, especially under-reporting, was common in children and adolescents with T1D: more than one-third of participants were classified as under-reporters and 10% as over-reporters. Age, z-BMI and male gender were associated with the risk of under-reporting (model R2 = 0.5). Waist circumference was negatively associated with the risk of over-reporting (model R2 = 0.25). Conclusions Children and adolescents with T1D frequently under-report their food intake. Age, gender and z-BMI contribute to identify potential under-reporters.

Aims To test the hypotheses that exogenous carbohydrate oxidation affects postprandial glycaemic profiles and 13C/12C breath test could be used for estimating insulin resistance (IR) and insulin sensitivity (IS) in youths with Type 1 Diabetes (T1D). Methods Non-randomized, cross-sectional study for repeated measures; fifteen youths (11–15 years) with T1D were enrolled. Respiratory exchanges were measured by indirect calorimetry after the ingestion of a mixed meal [13% protein, 29% fat, 58% carbohydrate (CHO; naturally enriched with [13C]carbohydrates)]. Total and exogenous CHOs oxidation was calculated by indirect calorimetry and 13C/12C breath test. IR and IS were calculated using estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS). Results The blood glucose Area Under the Curve (BG-AUC) was significantly associated with the amount of exogenous CHOs oxidized (r = −0.67, p Conclusions Assessing the capacity to oxidize exogenous CHOs (estimated by the differential of 13C/12C enrichment in the expired air at the breath test) could be used as a non-invasive surrogate marker of IR and IS in youths with T1D.

INTRODUCTION The aims of the PROBIT trial (clinicaltrials.gov: NCT03131284) were to prevent overweight or obesity occurring at two years of life, and improve feeding patterns during infancy. METHODS The trial compared 252 northern Italian newborns whose paediatricians offered their parents an educational programme from the child's birth to the age of two years (intervention arm) with 216 newborns whose parents did not undergo the programme (control arm). This sample size was 80% powerful to detect, with a 0.05 α error, a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm. At each well visit, the parents of the children in the intervention arm were given oral and written information about protective behaviours, with particular emphasis on responsive feeding. Overweight and obesity at two years of age were, respectively, defined as a body mass index of more than the 85th and the 95th percentile in accordance with the WHO growth charts. The sample size had 80% power to detect a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm. RESULTS At the age of two years, the prevalence of obesity in the intervention arm was 35% lower than among the controls, but the difference was not statistically significant (8.7% vs. 13.4%; p = 0.10) There was no difference in the prevalence of overweight/obesity between the groups (26.8% vs. 28.3%; p = 0.49). At the age of three months, a higher proportion of the infants in the intervention group were fed on demand (93% vs. 80%, p

Insulin resistance is a condition of gluco-metabolic sufferance that may hesitate in the further development of type 2 diabetes and cardiovascular disease. The development of insulin resistance is mostly associated with the accumulation of excessive fat in the body. The epidemic impact of obesity in the youngest promoted an increase of the prevalence of insulin resistance also in children and adolescents. Increased fat accumulation in the peri-visceral area of the abdomen, occurring preferably at and after puberty, and in the liver, as non-alcoholic fatty liver disease, plays a role in the process. After puberty, males are at higher risk than females to develop insulin resistance. Also ethnicity contributes to sensitivity of children to develop insulin resistance, where Hispanics, South-Asians, and Indians are at higher risk than Whites and Blacks.In spite of the research progress in the field, several questions on the relationship between body composition and insulin resistance are still unanswered. Multiomics approach, combined with nutrition as well as imaging techniques might contribute to unravel the role of body composition on insulin resistance.

Background and aims: We aimed to evaluate whether the metabolically healthy obese (MHO) phenotype was associated with hepatic steatosis (HS) or left ventricular hypertrophy (LVH) in young people with overweight (OW), obesity (OB) and morbid obesity (MOB) and whether the prevalence of these comorbidities was affected by OB severity. Methods and results: An abdominal ultrasound was performed in 1769 children and adolescents, mean age 10.6 years (range 5–18) with MHO phenotype, defined as the absence of traditional cardiometabolic risk factors, in order to identify HS. In a subsample of 177 youth the presence of LVH, defined by 95th percentile of LV mass/h 2.7 for age and gender, was also analyzed. The prevalence of HS increased from 23.0% in OW to 27.8% in OB and 45.1% in MOB (P < 0.0001). The proportion of LVH increased from 36.8% in OW to 57.9% in OB and 54.5% in MOB (P < 0.05). As compared with OW, the odds ratio (95% CI) for HS was 2.18 (1.56–3.05), P < 0.0001) in OB and 6.20 (4.26–9.03), P < 0.0001) in MOB, independently of confounding factors. The odds ratio for LVH was 2.46 (1.20–5.06), P < 0.025) in OB and 2.79 (1.18–6.61), P < 0.025) in MOB, as compared with OW. Conclusion: In spite of the absence of traditional cardiometabolic risk factors, the prevalence of HS and LVH progressively increased across BMI categories. MHO phenotype does not represent a “benign” condition in youth.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention. The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase. Electronic supplementary material The online version of this article (10.1186/s13052-018-0525-6) contains supplementary material, which is available to authorized users.

Background: Body Mass Index Italian reference data are available for clinical and/or epidemiological use, but no study compared the ability of this system to classify overweight and obesity and detect subjects with clustered cardiometabolic risk factors with international standards. Therefore our aim was to assess 1) the agreement among the Italian Society for Pediatric Endocrinology and Diabetology (ISPED), the World Health Organisation (WHO) and the International Obesity Task Force (IOTF) Body Mass Index cut-offs in estimating overweight or obesity in children and adolescents; 2) the ability of each above-mentioned set of cut-points to detect subjects with cardiometabolic risk factors. Methods: Data of 6070 Italian subjects aged 5-17 years were collected. Prevalence of normal-weight, overweight and obesity was determined using three classification systems: ISPED, WHO and IOTF. High blood pressure, hypertriglyceridemia, low high density lipoprotein-cholesterol and impaired fasting glucose were considered as cardiometabolic risk factors. Results: ISPED and IOTF classified more subjects as normal-weight or overweight and less subjects as obese as compared to WHO (p 0.900), while it differed for obesity definition, ranging from the highest agreement between ISPED and IOTF (k 0.875) to the lowest between ISPED and WHO (k 0.664). WHO had the highest sensitivity, while ISPED and IOTF systems had the highest specificity, in identifying obese subjects with clustered cardiometabolic risk factors. Analogous results were found in subjects stratified by gender or age. Conclusions: ISPED and IOTF systems performed similarly in assessing overweight and obesity, and were more specific in identifying obese children/adolescents with clustered cardiometabolic risk factors; on the contrary, the WHO system was more sensitive. Given the seriousness of the obesity epidemic, we wonder whether the WHO system should be preferable to the national standards for clinical practice and/or obesity screening.

Background and aims Hypertension (HTH) is a frequent complication in pediatric obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we compared the performance of a new index (High Blood Pressure index, HBPi) with respect to the standard criteria of the IV Report [systolic BP (SBP) and/or diastolic BP (DBP) ≥95th percentile for age, gender and height]. We also compared the performance of HBPi with other simplified indices such as the BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics' outpatient centers participating in the “CARdiometabolic risk factors in ITALY study” provided medical records of 4225 Ow/Ob children and adolescents (age 6–16 years). Methods and results Centers were divided into two groups: training set (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The simplified HBPi (mmHg) was: (SBP/2 + DBP/10) − age + (1 × female gender). In the TS, a HBPi value ≥57 mmHg in both children and adolescents had high sensitivity (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values in classifying youth at high risk of HTN compared with the IV Report. In the VS, the HBPi showed a better performance than high levels of BP/height ratio and height-specific BP thresholds in classifying individuals at risk of HTN: area under curves 0.95 (0.93–0.96), 0.80 (0.78–0.82), 0.76 (0.74–0.79), respectively; specificities 0.95 (0.94–0.96), 0.69 (0.67–0.72), 0.60 (0.57–0.62), respectively. Conclusions HBPi, combining SBP and DBP, gender and age, may help pediatricians to implement HTN screening in Ow/Ob youth.

To test the hypothesis that diet composition, adiposity and glycometabolic control could independently contribute to an increase in the cardiovascular risk (CVR) for children/adolescents with type 1 diabetes (T1D). One hundred and eighty children/adolescents with T1D (age range 5–18 years) were enrolled. Diet (3-day weighed dietary record), physical (height, weight, waist circumference, bioelectrical impedance analysis) and biochemical (HbA1c, lipid profile) parameters were recorded. Regression models, using non-HDL cholesterol (a gross index of CVR) as the dependent variable and HbA1c (mmol/mol), fat mass (FM) %, lipid-to-carbohydrate intake ratio as independent ones, were calculated. Non-HDL cholesterol was significantly associated with adiposity (FM%; r = 0.27, 95% CI 0.13–0.43), body fat distribution (waist-to-height ratio; r = 0.16, 95% CI 0.02–0.31), lipid intake [% of energy intake (EI)] (r = 0.25, 95% CI 0.11–0.41), carbohydrate intake (% EI; r = −0.24, 95% CI 0.10–0.40), lipid-to-carbohydrate intake ratio (r = 0.26, 95% CI 0.12–0.42) and blood glucose control (HbA1c; r = 0.24, 95% CI 0.10–0.40). A p value cutoff of 0.10 was used for covariates to be included in the regression analysis. Multiple regression analysis showed that adiposity (FM%), blood glucose control (HbA1c) and lipid-to-carbohydrate intake ratio independently contributed to explaining the inter-individual variability of non-HDL cholesterol (R 2 = 0.163, p

Maternal and placental conditions that are unfavourable for the embryo/foetus have long-lasting effects on different tissues and functions of the body, which may persist for life and, potentially, also be transmitted to the offspring. This review resumes current evidence on principle maternal and gestational conditions associated with unfavourable metabolic programming of the offspring, along with their mechanisms of action, either supposed or already proved.

The prevention, diagnosis and treatment of obesity-induced metabolic conditions are cornerstones of the management of overweight and obesity in adolescents. This paper reviews important new evidence in the field of the metabolic issues concerning the obese adolescent, with particular focus on epidemiological and clinical aspects. Current concepts and controversies regarding metabolic syndrome (MS), MS components and novel metabolic markers will be discussed, as well as two other conditions that increase the metabolic and cardiovascular risk in obese adolescents: polycystic ovary syndrome and non alcoholic fatty liver disease.

Summary What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents. What this study adds When applied to Italian cohorts of obese children and adolescents, the triglycerides cut-off of 1.17 mmol/L has similar validity as in the Canadian cohort to select patients who may present impaired glucose tolerance. Fasting plasma glucose and fasting triglycerides can be combined to obtain an accurate criterion to select obese children and adolescents who may present impaired glucose tolerance. Objectives We aimed to validate fasting triglycerides > 1.17 mmol L−1, a criterion recently proposed for selecting obese children at risk of impaired glucose tolerance (IGT), and to assess whether the accuracy of triglycerides (TG) can be improved by the use of other variables. Methods We studied an Italian cohort of 817 obese children and adolescents (8–18.4 years) who underwent clinical examination, fasting blood analysis and the oral glucose tolerance test (OGTT). The discriminative properties of TG > 1.17 mmol L−1 were assessed and compared with those observed in a Canadian cohort from which this criterion was derived: 71.4 [57.8–85.1]% sensitivity and 64.1 [57.7–70.4]% specificity. The possible contribution of other variables was evaluated by assessing the net reclassification improvement (NRI), i.e., the net increase in the percentage of subjects correctly classified. Results Thirty-nine children (4.7%) had IGT. The 1.17 mmol L−1 TG threshold showed 66.6 [51.8–81.4]% sensitivity and 68.2 [64.9–71.5]% specificity, thus successfully validated. Fasting plasma glucose (FPG) was independently associated with IGT (odds ratio = 3.86 [2.09–7.14], P 1.17 mmol L−1. Conclusions TG > 1.17 mmol L−1 is a useful criterion to detect roughly 66% of obese children with IGT through OGTT performed in about 33% of all obese children. However, the ‘TG≥1.13 mmol L−1 plus FPG≥4.44 mmol L−1’ criterion improved discrimination accuracy, leading to the possibility of detecting even more than 66% of obese children with IGT though limiting OGTT to just 25% of all obese children.

Context: Young-onset obesity is strongly associated with the early development of type 2 diabetes (T2D). Genetic risk scores (GRSs) related to T2D might help predicting the early impairment of glucose homeostasis in obese youths. Objective: Our objective was to investigate the contributions of four GRSs (associated with: T2D [GRS-T2D], beta-cell function [GRS-β], insulin resistance [GRS-IR], and body mass index) to the variation of traits derived from oral glucose tolerance test (OGTT) in obese and normal-weight children and young adults. Design: This was a cross-sectional association study. Patients: A total of 1076 obese children/adolescents (age = 11.4 ± 2.8 years) and 1265 normalweight young volunteers (age = 21.1 ± 4.4 years) of European ancestry were recruited from pediatric obesity clinics and general population, respectively. Intervention: Standard OGTT was the intervention in this study. Main Outcome Measures: Associations between GRSs and OGTT-derived traits including fasting glucose and insulin, insulinogenic index, insulin sensitivity index, disposition index (DI) and associations between GRSs and pre-diabetic conditions were measured. Results: GRS-β significantly associated with fasting glucose (β = 0.019; P = 3.5 × 10-4) and DI (β =-0.031; P = 8.9 × 10-4, last quartile 18%lower than first) in obese children, and nominally associated with fasting glucose (β = 0.009; P = 0.017) and DI (β =-0.030; P = 1.1 × 10-3, last quartile 11%lower than first) in normal-weight youths. GRS-T2D showed weaker contribution to fasting glucose and DI compared to GRS-β, in both obese and normal-weight youths. GRS associated with insulin resistance and GRS associated with body mass index did not associate with any traits. None of the GRSs associated with prediabetes, which affected only 4%of participants overall. Conclusion: Single nucleotide polymorphisms identified by genome-wide association studies to influence beta-cell function were associated with fasting glucose and indices of insulin secretion in youths, especially in obese children. (J Clin Endocrinol Metab 101: 4244-4250, 2016).

Several studies investigating the relationship between body mass index (BMI), waist circumference (WC), and/or body fat (BF) with macronutrient composition of the diet have suggested that dietary composition may play an important role to overweight/obesity in childhood, but its relation remains inconclusive. The aim was to assess the association between energy intake (EI) and macronutrient diet composition with overweight/obesity among children. Nonrandomized cohort study including 396 Italian children and preadolescents (9-13 years old), 200 overweight/obese and 196 normal-weight. The children's weight, height, WC, and food intake were measured. Reported EIwas higher in overweight/obese than in nonoverweight children; however, after body weight was considered, the overweight/obese children had less EI than their leaner counterparts. Percentages of EI from proteins, SFA, MUFA and PUFA (in males), and dietary fiber (g/1000 kcal) were higher in the overweight/obese children than in the leaner ones. EI from carbohydrates and fats was lower in overweight/obese males and females, respectively. Positive correlations between BMI and waist-to-height ratio with EI from proteins were found in males (r = 0.296, P, Spanish Ministry of Health and Consumption Affairs (Projects 14/00636, Red Predimed-RETIC RD06/0045/1004, and CIBEROBN CB12/03/30038), Grant of support to research groups no. 35/2011 (Balearic Islands Gov.), EU FEDER funds.

The aim of the present study was to build a predictive model of nonalcoholic fatty liver disease (NAFLD) in obese children. Fifty-six obese 10-year-old children underwent blood tests for biochemical measures and magnetic resonance imaging for NAFLD diagnosis. A model combining waist-to-height ratio, homeostasis model assessment of insulin resistance, adiponectin, and alanine aminotransferase was accurate in predicting NAFLD (AUROC = 0.94 [95% confidence interval 0.89-0.99], P

A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity. The oral glucose tolerance test (OGTT), the gold standard to diagnose this condition, may not be realistically performed in all patients due to discomfort, labor, and cost. The aim of this study was to assess whether one or more biochemical indexes measured in fasting conditions could be used to identify obese children at risk of IGT. A cohort of 563 white obese children and adolescents (M/F: 315/248; aged 4-17 years) was recruited and underwent anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of insulin resistance (HOMA(IR)) were tested in pursuit of a possible threshold to be used as a predictor of IGT. Thirty-seven children (6.9%) had IGT and one child (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA(IR) were all significantly higher in children with IGT than in children without IGT. Receiver-operating characteristic (ROC) curve analyses run for gender and puberty-adjusted FPG, FSI, and HOMA(IR) were all significant: area under the curve (95% confidence interval) equaled 0.68 (0.59-0.76), 0.66 (0.56-0.76), and 0.68 (0.59-0.78), respectively. The three parameters did not show significantly different sensitivity/specificity in the pooled population or in the gender/puberty subgroups. Thresholds varied among gender/puberty subgroups for FSI and HOMA(IR), but not for FPG, which showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG may be considered a screening tool to narrow clinical indication to OGTT in obese white children and adolescents.

Little is known on the relationship between obesity and hydration levels in children. This study assessed whether and by which mechanisms hydration status differs between obese and non-obese children. Hydration levels of 86 obese and 89 normal weight children (age: 7–11 years) were compared. Hydration was measured as the average free water reserve (FWR=urine output/24 h minus the obligatory urine output [total 24 h excreted solutes/97th percentile of urine osmolality of children with adequate water intake, that is, 830 mOsm/kg]) over 2 days. Three days of weighed dietary and fluid intakes were recorded. Non-parametric tests were used to compare variables that were skewed and to assess which variables correlated with hydration. Variables mediating the different hydration levels of obese and normal weight children were assessed by co-variance analysis. Obese children were less hydrated than normal weight peers [FWR=median (IQR): 0.80 (−0.80–2.80) hg/day vs 2.10 (0.10–4.45) hg/day, P

We assessed the prevalence and incidence of type 1 diabetes mellitus (T1DM) in Veneto Region in Italy. The average prevalence and incidence rates were 1.26/1000 subjects and 16.5/100,000 person-years, respectively. This study shows that the Veneto Region is an area with intermediate-high risk of T1DM.

The chapter contains a critical review of the current literature pertaining to the consequences of childhood and adolescent obesity/metabolic syndrome on the urogenital system, with a particular focus on microalbuminuria, renal disease, urolithiasis and lower urinary tract symptoms. The clinical implications of the current evidence with regard to the relationship between early obesity/metabolic syndrome and the above-mentioned conditions are discussed.

The Prader-Willi syndrome (PWS) is caused by lack of expression of paternal allele of the 15q11.2-q13 region, due to deletions at paternal 15q11.2-q13 (

Most of the complications of juvenile obesity are due to metabolic disturbances induced by an excessive accumulation of fat which leads to chronic diseases like type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Finding effective ways of identifying obese paediatric patients who are at increased risk of developing cardiovascular and metabolic complications has been recognised to be a promising strategy to improve prevention of complications of early obesity. Moreover, correctly identifying obese children who are already affected by metabolic co-morbidities should be a clinical priority. According to the state of the art summarised in this review, traditional metabolic variables included in the definitions of metabolic syndrome (MS), pre-diabetes, non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steato-hepatitis and, in obese girls, the presence of polycystic ovary syndrome are the best available longitudinal predictors of CVD and T2DM among obese children and adolescents. In clinical practice, traditional metabolic variables included in the definitions of MS should be assessed in all obese children and adolescents; fasting metabolic variables have been proposed to identify obese patients likely to be affected by impaired glucose tolerance or T2DM, and ultrasound has proved to be a valid surrogate for biopsy in the diagnosis of NAFLD. Further large longitudinal and cross-sectional studies are needed to improve our chances of identifying obese youth at the highest metabolic risk.

Objective To assess the accuracy of body mass index (BMI), Z score of the BMI, waist circumference, and waist-to-height ratio in selecting obese children with fasting metabolic impairments or impaired glucose tolerance. Study design In a cohort of 883 obese children and adolescents (age 8-18 years), we assessed the associations of anthropometric indices with traditional metabolic complications of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension, high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of anthropometric indices as markers of metabolic impairment was assessed by receiver operating characteristic analysis and the areas under the receiver operating characteristics curves (AUROCs) of anthropometric indices were compared with each other by the DeLong test. Results BMI, Z score of the BMI, waist circumference, and waist-to-height ratio were associated with metabolic impairments but showed low to moderate accuracy in discriminating both single and clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4 anthropometric indices did not show significantly different AUROCs as predictors of clustered metabolic risk factors (all P values of DeLong tests: >.05). Conclusions Commonly used anthropometric indices are not satisfactory markers of metabolic comorbidity among obese children and adolescents and should not be adopted as screening tools for the metabolic assessment of this category of patients.

What is already known about this subject Fasting triglycerides above 1.17 mmol/L have been shown to be useful to select obese children and adolescents who may present impaired glucose tolerance in a Canadian cohort. Fasting plasma glucose is associated with the risk to present impaired glucose tolerance in several cohorts of obese children and adolescents. What this study adds When applied to Italian cohorts of obese children and adolescents, the triglycerides cut-off of 1.17 mmol/L has similar validity as in the Canadian cohort to select patients who may present impaired glucose tolerance. Fasting plasma glucose and fasting triglycerides can be combined to obtain an accurate criterion to select obese children and adolescents who may present impaired glucose tolerance.We aimed to validate fasting triglycerides 1.17 mmol L(-1) , a criterion recently proposed for selecting obese children at risk of impaired glucose tolerance (IGT), and to assess whether the accuracy of triglycerides (TG) can be improved by the use of other variables.We studied an Italian cohort of 817 obese children and adolescents (8-18.4 years) who underwent clinical examination, fasting blood analysis and the oral glucose tolerance test (OGTT). The discriminative properties of TG 1.17 mmol L(-1) were assessed and compared with those observed in a Canadian cohort from which this criterion was derived: 71.4 [57.8-85.1]% sensitivity and 64.1 [57.7-70.4]% specificity. The possible contribution of other variables was evaluated by assessing the net reclassification improvement (NRI), i.e., the net increase in the percentage of subjects correctly classified.Thirty-nine children (4.7%) had IGT. The 1.17 mmol L(-1) TG threshold showed 66.6 [51.8-81.4]% sensitivity and 68.2 [64.9-71.5]% specificity, thus successfully validated. Fasting plasma glucose (FPG) was independently associated with IGT (odds ratio = 3.86 [2.09-7.14], P 0.001), besides TG. The bivariate criterion of TG ≥ 1.13 mmol L(-1) plus FPG ≥ 4.44 mmol L(-1) had a 69.2 [54.7-83.7]% sensitivity and a 78.2 [76.8-79.6]% specificity, thus displaying a 12.6% NRI (P 0.001) compared with TG1.17 mmol L(-1) .TG 1.17 mmol L(-1) is a useful criterion to detect roughly 66% of obese children with IGT through OGTT performed in about 33% of all obese children. However, the 'TG≥1.13 mmol L(-1) plus FPG≥4.44 mmol L(-1) ' criterion improved discrimination accuracy, leading to the possibility of detecting even more than 66% of obese children with IGT though limiting OGTT to just 25% of all obese children.

We performed a critical review focused on the main non-oncologic disorders that have a strong, direct association with obesity: chronic kidney disease, kidney stones and female and male lower urinary tract symptoms/disorders. We discuss the epidemiology, pathogenesis and therapeutic aspects regarding the association between obesity and non-diabetic and non-hypertensive forms of chronic kidney disease directly caused or worsened by weight excess, with particular attention on obesity-related glomerulopathy (ORG), which is typical of severe obesity, and the consequences of intentional weight loss on proteinuria and glomerular filtration rate. The associations of obesity with kidney stones and lower urinary tract conditions are also discussed from the epidemiological, physiopathological and therapeutical points of view, with emphasis on the principal concerns raised by the heterogeneity of study designs and outcome definitions typical of research in these fields. We also call attention to important clinical and scientific questions that should be addressed by future research.

To investigate the relationship between postprandial nutrient balance, satiety and hormone changes induced by two different meals taken after a moderate intensity exercise bout. Ten prepubertal obese children participated in the study. The experiment was designed as a cross-over study for repeated measures. Each test period lasted five consecutive hours during which the children were under medical supervision. The effects of two isocaloric meals were compared after a moderate intensity exercise (4 multiples of resting metabolic rate, 30 min, cycling): a low-fat/high-carbohydrate meal (meal A) and a high-fat/low-carbohydrate meal (meal B). Pre and postprandial (3 h) substrate oxidation, biochemical parameters, gastrointestinal hormone concentrations and appetite were measured. The main results were: (i) higher fat balance (5.1±5.0 vs −5.0±6.6 g, P=0.001) and lower carbohydrate balance after meal B than A (−9.7±13.3 vs 11.3±18.3 g, P

Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p < 0.001) without changing insulin/kg/day requirement. In the sub-group of patients with a significant HbA1c reduction (ΔHbA1c ≥ 0.5 %, n = 12), the carbohydrate (CHO) intake was significantly higher at follow-up (53.0 ± 4.0 vs 57.6 ± 2.5 %; p < 0.01); on the contrary, fat (31.3 ± 3.6 vs 28.5 ± 1.6 %; p < 0.05) and protein intake (15.4 ± 1.8 vs 13.3 ± 1.6 %; p < 0.01) significantly decreased. Patients without a significant HbA1c reduction did not show any difference. CHC, in combination with nutritional education, does not affect dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.