Feasibility and effectiveness of a distance-adapted physical activity intervention in adolescents with obesity during the COVID-19 pandemic.

BACKGROUND: Pediatric obesity represents one of the most important public health challenges and its prevalence significantly increased during the COVID-19 pandemic. Our prospective study aimed to assess the feasibility of a remote adapted physical activity (PA) intervention and its effectiveness in improving anthropometric indices, metabolic health parameters, as well as cardiopulmonary function and fitness in adolescents with obesity. METHODS: A PA intervention involving synchronous online lessons combined with asynchronous sessions and promotion of independent PA and "active breaks" to interrupt prolonged sedentary behaviors was proposed to 20 adolescents aged 11-17 years with obesity over a 4-month period. Clinical and anthropometric parameters (weight, height, waist, body composition, blood pressure), metabolic parameters (glycemia, insulinemia, glycated hemoglobin, oral glucose tolerance test [OGTT], lipid profile, presence of hepatic steatosis), cardiopulmonary function and fitness indices (VO2max, six-minute walking test [6MWT], upper and lower limb strength test) were evaluated before and after the intervention. RESULTS: Twenty adolescents with obesity were enrolled (11 male [55%], aged 14.1±1.5 years, BMI SDS 3.1±0.5). Eighteen participants (90%) successfully completed the project, and no adverse events were reported. We observed an increase in cardiovascular and muscle fitness [higher VO2peak, maximal workload, better performance at limb strength and 6MWT (all P<0.05)], increased lean body mass (P=0.005), and an improvement of glucose metabolism response with a reduction of insulin concentrations during OGTT (P=0.043). CONCLUSIONS: Participation in the training program was feasible and effective in improving cardiovascular fitness, glucose metabolism, body composition, strength, and endurance in adolescents with obesity during the COVID-19 pandemic.

Postprandial glucose metabolism in children and adolescents with type 1 diabetes mellitus: potential targets for improvement.

The main goal of therapeutic management of type 1 Diabetes Mellitus (T1DM) is to maintain optimal glycemic control to prevent acute and long-term diabetes complications and to enable a good quality of life. Postprandial glycemia makes a substantial contribution to overall glycemic control and variability in diabetes and, despite technological advancements in insulin treatments, optimal postprandial glycemia is difficult to achieve. Several factors influence postprandial blood glucose levels in children and adolescents with T1DM, including nutritional habits and adjustment of insulin doses according to meal composition. Additionally, hormone secretion, enteroendocrine axis dysfunction, altered gastrointestinal digestion and absorption, and physical activity play important roles. Meal-time routines, intake of appropriate ratios of macronutrients, and correct adjustment of the insulin dose for the meal composition have positive impacts on postprandial glycemic variability and long-term cardiometabolic health of the individual with T1DM. Further knowledge in the field is necessary for management of all these factors to be part of routine pediatric diabetes education and clinical practice. Thus, the aim of this report is to review the main factors that influence postprandial blood glucose levels and metabolism, focusing on macronutrients and other nutritional and lifestyle factors, to suggest potential targets for improving postprandial glycemia in the management of children and adolescents with T1DM.

The burden of low back pain in children and adolescents with overweight and obesity: from pathophysiology to prevention and treatment strategies.

Nonspecific low back pain (LBP) is one of the most common causes of disability, affecting all individuals at least once in their lifetime. Such a condition is also becoming increasingly frequent in the pediatric population, especially in children and adolescents with overweight/obesity. Furthermore, new-onset LBP during adolescence has been demonstrated to be a strong predictor of developing LBP later in life, contributing to poorer outcomes and increasing social and medical costs. Several causes and different mechanisms have been considered for the development of LBP in pediatric individuals affected by obesity. For this reason, planning adequate prevention and treatment strategies, mainly through conservative lifestyle changes, would be crucial to anticipate the negative consequences of persisting LBP in adulthood. The aim of this narrative review was to characterize the relationship between LBP and overweight/obesity in the pediatric population, highlighting epidemiological and pathophysiological aspects. In addition, prevention and treatment approaches will be reviewed considering the need to reduce the burden of LBP on this population. According to our search, LBP was more frequent in children and adolescents with overweight and obesity and has been associated with several anthropometric and lifestyle factors, including lumbar hyperlordosis, sedentary habits, physical inactivity, carrying a heavy schoolbag, low vitamin D levels, psychosocial ill-being, and premature intervertebral disc degeneration. Most of these conditions may be addressed with conservative strategies mainly consisting of dietary adjustments, physical exercise, education programs, and physical therapy.

Micronutrients in early life and offspring metabolic health programming: a promising target for preventing non-communicable diseases.

Chronic non-communicable diseases are the leading cause of morbidity and mortality worldwide. Developing and implementing effective preventive strategies is the best way to ensure the overall metabolic health status of the population and to counter the global burden of non-communicable diseases. Predisposition to obesity and other non-communicable diseases is due to a combination of genetic and environmental factors throughout life, but the early environment, particularly the environment during the fetal period and the early years of life, is crucial in determining metabolic health, hence the concept of 'fetal programming'. The origins of this causal link between environmental factors and disease lie in epigenetic mechanisms. Among the environmental factors, diet plays a crucial role in this process. Substantial evidence documented the key role of macronutrients in the programming of metabolic diseases early in life. Recently, the effect of maternal micronutrient intake on offspring metabolic health in later life emerged. The purpose of this narrative review is to bring to light available evidence in the literature on the effect of maternal micronutrient status on offspring metabolic health and underlying epigenetic mechanisms that drive this link to highlight its potential role in the prevention of non-communicable diseases.

IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes.

INTRODUCTION: Several genetic loci have been associated with diabetic nephropathy; however, the underlying genetic mechanisms are still poorly understood, with no robust candidate genes identified yet. AIM: We aimed to determine whether two polymorphisms, previously associated with renal decline, influence kidney impairment evaluating their association with markers of renal function in a pediatric population with type 1 diabetes (T1D). MATERIAL AND METHODS: Renal function was evaluated by glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in a cohort of pediatric subjects with T1D (n = 278). Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were assessed. The IGF1 rs35767 and PPARG rs1801282 SNPs were genotyped by TaqMan RT-PCR system. An additive genetic interaction was calculated. Association analysis between markers of renal function and both SNPs or their additive interaction were performed. RESULTS: Both SNPs showed a significant association with eGFR: the A allele of rs35767 or the C allele of rs1801282 were associated to reduced eGFR compared to G alleles. Multivariate regression analysis adjusted for age, sex, z-BMI, T1D duration, blood pressure and Hba1c values showed that the additive genetic interaction was independently associated with lower eGFR (ß = -3.59 [-6.52 to -0.66], p = 0.017). No associations were detected between SNPs, their additive interaction and ACR. CONCLUSIONS: These results provide new insight into the genetic predisposition to renal dysfunction, showing that two polymorphisms in IGF1 and PPARG genes can lead to a reduction in renal filtration rate leading these patients to be exposed to a higher risk of early renal complications.

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.

Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity.

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity.

Oral Microbiota in Children and Adolescents with Type 1 Diabetes Mellitus: Novel Insights into the Pathogenesis of Dental and Periodontal Disease.

The oral microbiota can be influenced by multiple factors, but only a few studies have focused on the role of glycemic control in determining early alterations of oral microbiota and their association with pathogenesis of both periodontitis and caries. The aim of this study is to evaluate the interplay between bacteria composition, oral hygiene, and glycemic control in a cohort of children with T1D. A total of 89 T1D children were enrolled (62% males, mean age: 12.6 ± 2.2 years). Physical and clinical characteristics, glucometabolic parameters, insulin treatment, and oral hygiene habits data were collected. Microbiological analysis was performed from saliva samples. A high prevalence of cariogenic and periodontopathogens bacteria in our cohort was detected. In particular, in all subjects Actinomyces spp., Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Lactobacillus spp. were isolated. S. mutans was found in about half of the analyzed sample (49.4%), in particular in patients with imbalance values of glycemic control. Moreover, a higher presence of both S. mutans and Veillonella spp. was detected in subjects with poorer glycemic control, in terms of HbA1c, %TIR and %TAR, even adjusting for age, sex, and hygiene habits as covariates. Virtuous oral hygiene habits, such as frequency of toothbrush changes and professional oral hygiene, negatively correlated with the simultaneous presence of Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis, red complex bacteria. Our study shows it is crucial to pay attention to glycemic control and regular oral hygiene to prevent the establishment of an oral microbiota predisposing to dental and periodontal pathology in subjects with T1D since childhood.

From Metabolic Syndrome to Type 2 Diabetes in Youth.

In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the ß-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered ß-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue ß-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.

A new proposal for a second insulin bolus to optimize postprandial glucose profile in adolescents with type 1 diabetes.

AIMS: To evaluate whether a second insulin bolus, calculated with a new approach, could improve postprandial glucose (PPG) after the intake of real-life high-fat (HF) and high-protein (HP) mixed meals. METHODS: Fifteen adolescents with T1D treated with non-automated insulin pumps and CGM were enrolled. Patients received standard, HF and HP mixed meals treated with one pre-meal insulin bolus; based on differences in PPG between standard, HF and HP meals, correction boluses were calculated (30% and 60% of pre-meal bolus for HF and HP meals, respectively). Then patients received the same HF or HP meal treated with pre-meal bolus plus second insulin bolus after 3 h. Differences between postprandial variables after HF and HP meals treated with one or two insulin boluses were assessed by paired Student's t-test. RESULTS: Treating HF and HP meals with two insulin boluses significantly reduced the postprandial BG-AUC (21% and 26% respectively, p < 0.05), increased %TIR (from 52.5 to 78.3% for HF meal; from 32.7 to 57.1% for HP meal; p < 0.01), and reduced mean BG and %TAR (p < 0.01), with no differences in %TBR. CONCLUSIONS: The new way to calculate and administer correction boluses 3 h after HF and HP meals is effective and safe in reducing PPG and the hypoglycemia risk.

Pros and Cons of Current Diagnostic Tools for Risk-Based Screening of Prediabetes and Type 2 Diabetes in Children and Adolescents with Overweight or Obesity.

It is still a matter of debate which is the most suitable diagnostic test for risk-based screening of prediabetes and type 2 diabetes (T2D) in children and adolescents with overweight or obesity. This review highlighted benefits and pitfalls of currently recommended screening tools (fasting plasma glucose [FPG], oral glucose tolerance test [OGTT], glycated hemoglobin A1c [HbA1c]). The greatest advantage of OGTT is the ability to detect people with impaired glucose tolerance, a subcategory at high risk of developing both T2D and cardiovascular disease. Important disadvantages are low reproducibility and inconvenience. FPG measurement is more practical, as it needs only one blood draw, although both OGTT and FPG require fasting. The reliability of HbA1c as a screening tool has been questioned, especially in children and adolescents, but its undeniable convenience can lead to increased adherence to screening. In contrast, it can be altered by several nonglycemic factors. Importantly, none of these tests have been validated in the pediatric population. Alternative tests have been recently proposed, including new OGTT-derived biomarkers and additional nonfasting glycemic markers. In conclusion, when choosing the most suitable test in clinical practice, advantages and disadvantages should be considered, as well as the possibility of performing different tests at once.

Cardiovascular Risk Factors in Children and Adolescents with Type 1 Diabetes Mellitus: The Role of Insulin Resistance and Associated Genetic Variants.

INTRODUCTION: Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular disease. Insulin resistance is an important cardiovascular risk factor (CVRF), also in subjects with T1D, but the influence of the genetic predisposition of insulin resistance on cardiovascular risk is still unknown in T1D. We aimed to determine whether a genetic score composed of six variants, previously associated with insulin resistance and type 2 diabetes (T2D) risk, associates with insulin sensitivity and known CVRFs in children and adolescents with T1D. MATERIALS AND METHODS: 330 children and adolescents (174 males; mean age 15.7 ± 3.5 years) with T1D were genotyped for the following genetic variants: rs1801278 (IRS1), rs1044498 (ENPP1), rs2295490 (TRIB3), rs1801282 (PPARG), rs780094 (GCKR), and rs35767 (IGF1). An additive genetic risk score (GRS) and cardiovascular risk score (CVRS) were calculated. Anthropometric, glycemic control, insulin sensitivity, blood pressure, and biochemical parameters were assessed. Multivariate regression between evaluated phenotypes and GRS was performed. RESULTS: We found a significant association between the GRS and estimated insulin sensitivity (ß = -0.027 [-0.040 to -0.013], R2 = 0.86, p≤ 0.001), diastolic blood pressure (ß = 0.68 [0.08-1.27], R2 = 0.20, p = 0.026), triglycerides (ß = 4.26 [1.74-6.77], R2 = 0.13, p = 0.001), waist to height ratio (ß = 0.003 [0.001-0.006], R2 = 0.75, p = 0.010), non-HDL-cholesterol (ß = 3.63 [1.39-5.87], R2 = 0.12, p = 0.002), and CVRS (ß = 0.063 [0.008-0.118], R2 = 0.19, p = 0.025), independent of age, sex, BMI, pubertal stage, diabetes duration, glycated hemoglobin, type of treatment, and total insulin requirement. The addition of the GRS to established clinical risk factors significantly improved the discriminatory capability of the regression model for predicting subjects with more CVRFs (C-statistic 0.89 [95% CI: 0.84-0.95] versus 0.83 (0.73-0.93); p = 0.037). CONCLUSIONS: Insulin resistance and T2D risk-associated genetic variants influence insulin sensitivity and known CVRFs in children and adolescents with T1D.

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.

A Gain-of-Function Mutation on BCKDK Gene and Its Possible Pathogenic Role in Branched-Chain Amino Acid Metabolism.

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the BCKDK gene in a neonate, picked up by newborn screening, with a biochemical phenotype of a mild form of maple syrup urine disease (MSUD). The same biochemical and genetic picture was present in the father. Computational analysis of the mutation was performed to better understand its role. Extensive atomistic molecular dynamics simulations showed that the described mutation leads to a conformational change of the BCKDK protein, which reduces the effect of inhibitory binding bound to the protein itself, resulting in its increased activity with subsequent inactivation of BCKDC and increased plasmatic branched-chain amino acid levels. Our study describes the first evidence of the involvement of the BCKDK gene in a mild form of MSUD. Although further data are needed to elucidate the clinical relevance of the phenotype caused by this variant, awareness of this regulatory activation of BCKDK is very important, especially in newborn screening data interpretation.

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.

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy.

Introduction: Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients. Methods: We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020. Results: Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the BTD gene identified 17 different genotypes and one mutation not previously known. Discussion: Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype-phenotype correlation.

The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age.

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.