The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery.

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.

Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes.

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.

FADS cluster variants are associated with insulin sensitivity in children and adolescents with overweight and obesity.

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.

Serum zonulin as an index of glucose dysregulation in children and adolescents with overweight and obesity.

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 (ß = -0.243; p = 0.019) and age (ß = -0.307; p = 0.004), independent of sex and BMI SDS [R2  = 0.16; p = 0.005]. Our results show an association between serum zonulin concentration and oral disposition index supporting the hypothesis of increased intestinal permeability as a possible risk factor for glucose metabolism dysregulation in children and adolescents with obesity.

Sex differences in cardiovascular risk factors of children and adolescents with type 1 diabetes mellitus: A role for diet?

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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]. CONCLUSIONS: 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.

Educational Intervention of Healthy Life Promotion for Children with a Migrant Background or at Socioeconomic Disadvantage in the North of Italy: Efficacy of Telematic Tools in Improving Nutritional and Physical Activity Knowledge.

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 < 0.001). At the Obesity Pediatric Clinic, after 6 months, pre-post-intervention variation in their consumption of vegetables and fruit was +14% (p < 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.

Nutritional Strategies for Childhood Obesity Prevention.

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.

Type 2 diabetes in pediatrics.

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.

Lipid and saturated fatty acids intake and cardiovascular risk factors of obese children and adolescents.

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.

Cardiovascular risk factors in children and adolescents with type 1 diabetes in Italy: a multicentric observational study.

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: 2021 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.

13C/12C breath test ratio after the ingestion of a meal naturally enriched with (13C)carbohydrates is a surrogate marker of insulin resistance and insulin sensitivity in children and adolescents with Type 1 Diabetes.

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 < 0.02) when adjusting for CHOs intake and %fat mass. A direct correlation between eGDR and ISS with exogenous CHOs oxidized (r = 0.70, p < 0.02; r = 0.61, p < 0.05 respectively) and with the differential of 13C/12C enrichment in the expired at breath test (r = 0.59, p < 0.05; r = 0.62, p < 0.05), was found. 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.

Nonalcoholic Fatty Liver Disease and Estimated Insulin Resistance in Obese Youth: A Mendelian Randomization Analysis.

CONTEXT: Nonalcoholic 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. OBJECTIVE: To test the hypothesis that NAFLD is causally related to IR. DESIGN AND METHODS: We 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). RESULTS: Nonalcoholic fatty liver disease prevalence increased by 20% for every increase in the GRS (ß-coefficient = 0.20, P < 0.001), and NAFLD was associated with ln-HOMA-IR (ß-coefficient = 0.28, P < 0.001). Thus, the expected increase in ln-HOMA-IR for every increase in the GRS (expected ß-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 (ß-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. CONCLUSIONS: Our 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.

Nutrition habits of children and adolescents with type 1 diabetes changed in a 10 years span.

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 < 0.001) higher protein and lipids intake and lower total carbohydrate and fiber intake than group A. HbA1c was significantly (P < 0.01) lower in group B than in group A. Logistic regression analysis showed that MUFA (OR 0.83, 95%CI:0.693-0.998), fiber intake (OR 0.82, 95%CI:0.699-0.0969), and technology use (OR 0.15, 95%CI:0.031-0.685), adjusted for age, gender, BMI, energy intake and diabetes duration, were associated with a HbA1c higher than 58 mmol/mol) (R2 = 0.27, P < 0.05). CONCLUSIONS: In a 10-year period, diet composition of children and adolescents with T1D changed and glucometabolic control improved. Fiber and MUFA intake showed a positive effect on HbA1c, independent from technology use, supporting the importance of educating children with T1D and families to maintain healthy eating habits.

Policaptil Gel Retard Intake Reduces Postprandial Triglycerides, Ghrelin and Appetite in Obese Children: A Clinical Trial.

The aim of this study is to test the hypothesis that the intake of Policaptil Gel Retard® (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 × 240 min/Dl) and appetite (-234 (274) vs. 36 (329)) than children assuming placebo. The AUC of ghrelin was significantly lower after PGR ingestion, than after placebo (-8179 (8073) vs. -2800 (7579) pg × 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.

Systemic anti-oxidant capacity is inversely correlated with systolic blood pressure and pulse pressure in children with obesity.

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: The systemic anti-oxidant capacity is inversely associated with systolic blood pressure and pulse pressure in children and adolescents with obesity.

Treatment of Metabolic Syndrome in Children.

The Metabolic Syndrome may be tentatively defined as the clustering of several metabolic risk factors in the same individual. A progressively higher number of children and adolescents is affected by this syndrome worldwide, mainly as a consequence of the constant increase of the prevalence of obesity and sedentary habits. As obesity, the chance that the metabolic syndrome traks into adulthood is high. Moreover, the evidence of an association between the duration of the exposition to metabolic risk factors and morbidity and mortality justifies early treatment and prevention of the metabolic syndrome in both children and adolescents. Treatment includes behavioral interventions, adequate nutrition and physical activity, and, if necessary, pharmacological treatments aimed at reducing excessive weight, dyslipidemia, hypertension, and glucose impairments. A multidisciplinary and staged approach to treatment, which includes pediatrician, mental health practitioner, dietician, and nurses, is crucial. Usually, the reduction of fat mass promotes an overall improvement of all the components of the metabolic syndrome. Nevertheless, every single component of the metabolic syndrome should be treated as quickly as possible, by using the best current practice. Drugs may be necessary for treating hypertension, type 2 diabetes mellitus and dyslipidemia. In selected cases of gross obesity resistant to treatment, surgical therapy may be also performed.

Vitamin D affects insulin sensitivity and ß-cell function in obese non-diabetic youths.

OBJECTIVE: Vitamin D may potentially play a central role in glucose homeostasis and ß-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 < 0.05). BVD was positively correlated with total vitamin D (P < 0.001) and negatively with BMI SDS (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.

"IGT-like" status in normoglucose tolerant obese children and adolescents: the additive role of glucose profile morphology and 2-hours glucose concentration during the oral glucose tolerance test.

OBJECTIVE: 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 ß-cell function (disposition index: DI). SUBJECTS, METHODS, AND MAIN OUTCOME MEASURE: 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 ß-cell function in "biphasic" versus "monophasic" patients. RESULTS: 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 ß-cell function, modeled as proportional control, than those with a biphasic shape (p = 0.031). CONCLUSIONS: 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.

Minor diplotypes of FMO3 might protect children and adolescents from obesity and insulin resistance.

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.