Search

Background Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. Aims To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. Methods A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype–phenotype association analysis were performed. Results The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and − 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and − 0.286, respectively). Conclusions These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.

Changes in the desaturation activity of LC-PUFAs may influence insulin sensitivity by modulating the relative abundance of omega-3. The aim of this cross-sectional study was to assess the association between genetic variants of fatty acid desaturase cluster genes (FADS1, FADS2, FADS3) and insulin sensitivity in a cohort of children and adolescents with obesity. Anthropometric evaluation, lipid profile, glucose metabolism parameters and the genotype of rs1535 on FADS2 gene were assessed. In 162 obese children and adolescents (12.6 ± 2.3 years; BMI 30.9 ± 7.3), we found a significant association between an index of insulin sensitivity, i.e., Matsuda index, and rs1535 (B = -0,192; p = 0.008), BMI (B = -0,003; p 0.001), and triglycerides (B = -0,034; p 0.001), independent of age and sex [R² = 0.35; p = 0.001]. In conclusion, FADS cluster variants were associated with insulin sensitivity in a population of children and adolescents with obesity, contributing to identify individuals who may benefit from personalised prevention and treatment nutritional strategies since childhood.

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.

The MiniMed™ 670G insulin pump was the first hybrid closed-loop (HCL) system available for clinical use. Data on metabolic outcomes in children, adolescents and young adults over the first 12 months with auto-mode use of this device are available, but no data with longer follow-up have been published. We aimed to assess the metabolic outcomes in children and adolescents using the MiniMed™ 670G for 24 months.

Increased intestinal permeability has an important role in metabolic dysregulation. In this cross-sectional study, we examined whether serum intestinal permeability marker zonulin and related pro-inflammatory molecules were associated with the oral disposition index, a predictor for the development of type 2 diabetes, in a cohort of children and adolescents with overweight and obesity. Ninety-two children and adolescents were recruited [Male: 43; 12.7 (2.35) years; BMI SDS: 2.7 (0.96)]. Anthropometric and clinical parameters, lipid profile, glucose metabolism and plasma levels of zonulin, lipopolysaccharide-binding protein and Interleukin-6 were measured. We found an association between oral disposition index and zonulin (β = -0.243; p = 0.019) and age (β = -0.307; p = 0.004), independent of sex and BMI SDS [R

N/A

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.

Background: Reducing the spread of obesity represents a challenge for clinicians in which obesity prevention plays a key role in achieving this purpose. The aim of this review is to analyze the nutritional interventions that can be implemented to prevent childhood obesity. Methods: Searching PubMed and Cochrane Library between 2019 and 2021. Further searching with no date range for articles selected for their specific relevance in the pediatric area or for their scientific relevance. A total of 871 articles were identified and 90 were included. Results: We organized the results of the selected articles into age groups, and according to the subjects targeted for interventions or to the site of interventions, reserving an in-depth analysis on specific nutritional aspects. Promotion of breastfeeding, reduction of protein content of formulated milks, and diet of the first 12–24 months, involving family and schools in interventions that promote physical activity and healthy diet, are promising strategies for reduction of the risk of obesity. To increase the efficacy of interventions, a multidimensional approach is crucial. Conclusions: A multidimensional approach, which takes into consideration different areas of intervention, is pivotal for childhood obesity prevention. Integrated programs involving several components (nutrition and physical activity at first) at different levels (individual, family, school, and institutional) are crucial.

The aim of the “Smuovi La Salute” (“Shake Your Health”) project was to implement an integrated and comprehensive model to prevent and treat overweight and obesity in low socioeconomic status (SES) and minority groups living in three different districts in the north of Italy. An app and a cookbook promoting transcultural nutrition and a healthy lifestyle were developed, and no-cost physical activities were organized. Healthy lifestyle teaching was implemented in 30 primary school classrooms. Learning was assessed through pre- and post-intervention questionnaires. At the Obesity Pediatric Clinic, overweight and obese children of migrant background or low SES were trained on transcultural nutrition and invited to participate in the project. Primary school students increased their knowledge about healthy nutrition and the importance of physical activity (p-value &lt, 0.001). At the Obesity Pediatric Clinic, after 6 months, pre–post-intervention variation in their consumption of vegetables and fruit was +14% (p &lt, 0.0001) and no variation in physical activity habits occurred (p = 0.34). In this group, the BMI z-score was not significantly decreased (−0.17 ± 0.63, p= 0.15). This study demonstrates the feasibility and efficacy of telematic tools and targeted community approaches in improving students’ knowledge with regard to healthy lifestyle, particularly in schools in suburbs with a high density of migrants and SES families. Comprehensive and integrated approaches provided to the obese patients remain mostly ineffective.

iNtrOdUctiON: type 2 diabetes (t2d) in adolescents has become an increasing health concern throughout the world and its prevention and screening should be implemented in pediatric care. as clinical features at presentation, in some cases can be similar to type 1 diabetes and family history can be in favor of a monogenic form of diabetes, it is pivotal for physicians to be aware of youth-onset T2D specificities to ensure an accurate diagnosis. EVIDENCE ACQUISITION: We conducted the first search in Medline, Embase, Web of Science, using different keywords and their compositions. The keywords used, also called “mesh” (MEdical Subject Headings) on PubMed, are the following: “type 2 diabetes” AND (“child*” OR “pediatr*” OR “adolesce*”) AND (“epidem*” OR “diagnos*” OR “treat*” OR “complication” OR “comorbidit*”). International review, systematic reviews and meta-analyses, randomized control trials and case reports published between May 2018 and February 2021 were considered, to identify publications that deal with the topic. No restrictions were applied regarding the published paper’s language. eVideNce sYNtHesis: the global increase of overweight and obesity can complicate the diagnostic process and makes it essential to apply a systematic approach to each new diagnosis. Microvascular complications may be present at the time of diagnosis and chronic complications are frequent and need to be screened regularly. regular screening of comorbidities should also be performed. childhood t2d should be followed up by pediatric diabetes units to avoid diagnostic errors and delay in care. cONcLUsiONs: a multidisciplinary approach, by an experienced team, is pivotal to provide treatment options targeting the unique needs of pediatric patients. treatment programs must include the whole family and address all the aspects of the care (lifestyle, pharmacological therapy, psychological aspects, complications and comorbidities). an organized process of transition to adult care is essential.

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 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

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.

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.

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.

Background. Skipping breakfast has been associated with a higher risk of obesity and cardiovascular (CV) risk factors. However, it is not known if skipping breakfast is also correlated with CV risk factors independently from obesity. The mechanisms explaining the role of skipping breakfast on promoting fat accumulation as well as CV risk are not known. Hormones, in particular, insulin-like growth factor-1 (IGF-1), may potentially play a role in the metabolic profile of breakfast skippers. Aim. This cross-sectional study aims to test, in a sample of overweight/obese children, the hypotheses that skipping breakfast is associated with a worse metabolic profile and that IGF-1 levels are associated with this unfavorable metabolic profile. Methods and Results. We enrolled 112 overweight/obese prepubertal children (3–12 years). Anthropometric characteristics (height SDS, weight SDS, and body mass index (BMI) z-score) were measured. Blood samples were collected to evaluate glucose and lipid metabolisms and hormone profile (growth hormone (GH), IGF-1, insulin, and cortisol). The triglycerides/high-density lipoprotein (HDL) cholesterol ratio was calculated as a predictor of cardiovascular risk. Children were divided into two groups according to breakfast habits: consumers (≥5 weekly; N = 76) and skippers (≤4 weekly; N = 36). Glycaemia, total and low-density lipoprotein (LDL) cholesterol, triglycerides (p<0.05), and triglycerides/HDL cholesterol ratio (p<0.001) were higher, while HDL cholesterol was lower (p<0.01) in skippers as compared to consumers. IGF-1 concentrations were inversely correlated with LDL cholesterol (r = −0.279, p=0.013) and directly correlated with HDL cholesterol (r = 0.226, p=0.047). IGF-1 correlated positively with HDL cholesterol (r = 0.266, p=0.045) in consumers and correlated negatively with LDL cholesterol (r = −0.442, p=0.024) in skippers. Breakfast consumption among prepubertal overweight/obese children showed a better lipid profile in comparison with those who skipped breakfast [OR: 0.165 (95% CI: 0.053–0.518), p=0.001]; these latter odds of the increased triglycerides/HDL cholesterol ratio was 6.1-fold higher. Conclusions. Breakfast skippers show a worse lipid profile when compared to breakfast consumers. IGF-1 might play a role as an independent modulator of lipid metabolism.

Aims to assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods 2,021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS>+2SD, blood pressure>90th percentile, LDL cholesterol>100 mg/dl) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications. This article is protected by copyright. All rights reserved.

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.

The aim of this study is to test the hypothesis that the intake of Policaptil Gel Retard&reg, (PGR) is able to affect appetite, metabolic and hormonal postprandial profile in obese children. 46 obese children were randomly assigned to treatment with PGR or placebo, in a double blind clinical trial. Two PGR tablets or placebo were given in fasting condition, before the ingestion of a mixed meal (15 kcal/kg lean body mass). Blood samples were taken at baseline and for 4 hours, for measuring blood lipids, glucose, insulin, ghrelin, and glucagon like peptide-1 (GLP-1). Appetite was quantified using a visual analog scale. Children assuming PGR had a significantly lower increase of postprandial triglycerides (area under the curve (AUC): 3021 (2879) vs. 5038 (3738) mg &times, 240 min/Dl) and appetite (&minus, 234 (274) vs. 36 (329)) than children assuming placebo. The AUC of ghrelin was significantly lower after PGR ingestion, than after placebo (&minus, 8179 (8073) vs. &minus, 2800 (7579) pg &times, 240 min/mL). Blood glucose, insulin, non-esterified fatty acids (NEFA) and GLP-1 profiles were not significantly different in the two groups. In conclusion, a single intake of two tablets of PGR was associated with a significant reduction of appetite, ghrelin, and triglycerides in the postprandial period in obese children. Further investigation will assess if a chronic intake of PGR may affect body weight and glucose metabolism.

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.

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

We aimed to assess in obese youths the relationships between interleukin-6 (IL-6), fat meal-induced endotoxemia and glucose homeostasis. Twenty obese children/adolescents (9-17 years old, 11 boys) underwent a standard oral glucose tolerance test and, 7-14 days later, a 5-h fat meal test (fat=69% of energy, saturated/monounsaturated/polyunsaturated fatty acids=31.5%/35%/33.5%), with serial measures of IL-6 and two markers of lipopolysaccharide (LPS) exposure and translocation, LPS-binding protein (LBP) and soluble CD14 (sCD14). IL-6 correlated not only with basal (homeostatic model assessment-insulin resistance) but also with post-prandial (Matsuda index) insulin sensitivity (r=0.61 (0.24-0.82), P=0.005, r=-0.53 (0.12-0.78), P=0.03, respectively). IL-6 did not change after the meal whereas LBP and sCD14 decreased significantly, indicating LPS translocation. Neither basal sCD14 and LBP nor their incremental concentrations correlated with IL-6 or glucose homeostasis. In our sample, IL-6 was associated with insulin sensitivity but not with LPS exposure, suggesting that meals with a balanced content of saturated/monounsaturated/polyunsaturated fatty acids may not be associated with LPS-induced inflammation and metabolic impairment.

Obesity is a pro-atherogenic condition and postprandial lipoprotein profile and circulating cytokines changes may contribute to promote the process. The aim of this study is to investigate postprandial metabolic response, lipoprotein oxidation and circulating cytokine levels, after the ingestion of two different meals with different fat/carbohydrate ratio.Ten prepubertal obese boys consumed two meals with the same energy and protein content but with a different carbohydrate to fat ratio: 1) moderate fat (MF): 61% carbohydrate, 27% fat; 2) high fat (HF): 37% carbohydrate, 52% fat. The AUC of glucose and insulin were significantly (p0.05) lower after the HF meal. HF meal was followed by a significant decrease in the cholesterol carried in the HDL fractions, while cholesterol in the small, dense LDL and in the VLDL particles increased, as compared to baseline (p0.05 for all). No differences were found in the cholesterol distribution after the MF meal. Moreover, HDL-C concentration was lower (p0.05) at 300 min after HF vs. MF meal. Oxidized LDL (ox-LDL) concentration increased after the HF meal but not after the MF meal [9.3(2.2) vs 1.8(2.2)% from baseline, P0.02)]. A positive association (r0.3, P0.05) was observed between the densest LDL particles and the ox-LDL plasma levels. A reduction of IL-6 was found at 120 min after the MF [-23.3(5.5) vs -8.4(3.8)% from baseline, P0.05)] compared with the HF meal.A simple change of ≈25% of energy load from fat to carbohydrate in a meal significantly improves postprandial pro-atherogenic factors in obese boys.

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

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

Skipping breakfast influences cognitive performance. The aim of our study was to investigate the relationship between the variation of hormonal and metabolic postprandial parameters induced by breakfast consumption or fasting and cognitive performance in obese children. Cross-sectional study for repeated measures. Memory and attention assessment tests, hormones and nutrient oxidation were measured before and after consuming breakfast vs fasting in 10 prepubertal obese children. Fasting induced a significant (P