Time In Tight Range in children and adolescents with type 1 diabetes: A cross-sectional observational single centre study evaluating efficacy of new advanced technologies.

INTRODUCTION: Early and tight glycaemic control is crucial to prevent long-term complications of Type 1 Diabetes (T1D). The aim of our study was to compare glucose metrics, including Time In Tight Range (TITR), in a real-world setting. METHODS: We performed a single-centre cross-sectional study in 534 children and adolescents with T1D. Participants were divided into four groups (multiple daily injections + real-time Continuous glucose monitoring (CGM), multiple daily injections + intermittently scanned CGM, sensor augmented pump (SAP), and Advanced Hybrid Closed-Loop (AHCL). Demographical and clinical data were collected and analysed. RESULTS: The group with AHCL showed significantly higher Time In Range (TIR) (71.31% ± 10.88) than SAP (57.82% ± 14.98; p < 0.001), MDI + rtCGM (54.56% ± 17.04; p < 0.001) and MDI + isCGM (52.17% ± 19.36; p < 0.001) groups with a lower Time Above Range (p < 0.001). The group with AHCL also showed lower Time Below Range than MDI + isCGM and SAP groups (p < 0.01). The overall TITR was 37% ± 14 with 19% of participants who reached a TITR ≥50% with a mean TIR of 81%. AHCL had significantly higher TITR (45.46% ± 11.77) than SAP (36.25% ± 13.53; p < 0.001), MDI + rtCGM (34.03% ± 13.89; p < 0.001) and MDI + isCGM (33.37% ± 15.84; p < 0.001) groups with a lower Coefficient of Variation (p < 0.001). CONCLUSIONS: Our study indicates that AHCL ensures a better glycaemic control with an improvement in both TIR and TITR, along with a reduction in CV. Implementation of automated insulin delivery systems should be considered in the treatment of children and adolescents with T1D.

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children.

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

Insulin Clearance at the Pubertal Transition in Youth with Obesity and Steatosis Liver Disease.

No data are available on insulin clearance (ClI) trends during the pubertal transition. The aim of this study was to investigate in 973 youths with obesity whether ClI in fasting and post-oral glucose challenge (OGTT) conditions varies at the pubertal transition in relation to the severity of obesity and the presence of steatosis liver disease (SLD). The severity of obesity was graded according to the Centers for Disease Control. SLD was graded as absent, mild and severe based on alanine amino transferase levels. ClI was defined as the molar ratio of fasting C-peptide to insulin and of the areas under the insulin to glucose curves during an OGTT. In total, 35% of participants were prepubertal, 72.6% had obesity class II, and 52.6% had mild SLD. Fasting ClI (nmol/pmol × 10-2) was significantly lower in pubertal [0.11 (0.08-0.14)] than in prepubertal individuals [0.12 (0.09-0.16)] and higher in class III [0.15 (0.11-0.16)] than in class I obesity [0.11 (0.09-0.14)]. OGTT ClI was higher in boys [0.08 (0.06-0.10)] than in girls [0.07 (0.06-0.09)]; in prepubertal [0.08 (0.06-0.11)] than in pubertal individuals [0.07 (0.05-0.09)]; in class III [0.14 (0.08-0.17)] than in class I obesity [0.07 (0.05-0.10)]; and in severe SLD [0.09 (0.04-0.14)] than in no steatosis [0.06 (0.04-0.17)]. It was lower in participants with prediabetes [0.06 (0.04-0.07)]. OGTT ClI was lower in youths with obesity at puberty along with insulin sensitivity and greater secretion. The findings suggest that the initial increase in ClI in youth with severe obesity and SLD is likely to compensate for hyperinsulinemia and its subsequent decrease at the onset of prediabetes and other metabolic abnormalities.

Low Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity.

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the "Bambino Gesù Children Hospital", a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = -0.31, p < 0.001, BCa 95% -0.38, -0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = -0.33, p = 0.008, BCa 95% -0.53, -0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = -0.003 (-0.007, -0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and <0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and <0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.

Estimated insulin sensitivity, cardiovascular risk, and hepatic steatosis after 12 years from the onset of T1D.

AIM: To test the hypothesis that intensive insulin treatment and optimal glycaemic control are not fully protective against reduction of insulin sensitivity in children with type 1 diabetes. MATERIAL AND METHODS: Cohort study of 78 normal-weight patients with prepubertal onset (T0 ) and follow-up waves at 1 (T1 ), 5 (T5 ), 10 (T10 ), and 12 (T12 ) years; matched for age and sex to 30 controls at T12 . Estimated insulin sensitivity (eIS) by three formulae; ultrasound evaluation of para and perirenal fat thickness; hepatic steatosis (HS); carotid intima media thickness (cIMT) at T12 . RESULTS: At T12, the 36 patients (46%) who had constantly or prevalently haemoglobin A1c (HbA1c) < 58 mmol/l during follow-up showed better eIS indexes (p = 0.049 to <0.0001); lipid profile (p = 0.042 to <0.0001), reduced fat mass (p = 0.012) and required lower insulin dose (p = 0.032) than the 42 patients (54%) with HbA1c ≥ 58 at T12. Patients (N = 25) with eISEDC  < 8.77 mg kg-1  min-1 showed higher cIMT (p < 0.0001). HS was found in 6 patients (∼8%). In patients and normal-weight controls, fat mass (p = 0.03), age (p = 0.03), cIMT (p = 0.05) predicted HS; eIS indexes (p from 0.04 to <0.0001) predicted cIMT. Body mass index, perirenal fat, fat mass, and triglycerides to high density lipoprotein cholesterol ratio were associated with eIS indexes (p from 0.03 to <0.0001). CONCLUSIONS: Young T1D patients have reduced insulin sensitivity and higher cIMT. Adiposity, glucose, and lipid control over follow-up are likely to influence both. Enhanced adiposity seems of paramount relevance for the onset of HS in T1D patients alike in healthy youths.

Pathophysiology of Type 1 Diabetes and Gut Microbiota Role.

Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet ß-cells, resulting in a marked loss of ß-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.

Functional and Taxonomic Traits of the Gut Microbiota in Type 1 Diabetes Children at the Onset: A Metaproteomic Study.

Type 1 diabetes (T1D) is a chronic autoimmune metabolic disorder with onset in pediatric/adolescent age, characterized by insufficient insulin production, due to a progressive destruction of pancreatic ß-cells. Evidence on the correlation between the human gut microbiota (GM) composition and T1D insurgence has been recently reported. In particular, 16S rRNA-based metagenomics has been intensively employed in the last decade in a number of investigations focused on GM representation in relation to a pre-disease state or to a response to clinical treatments. On the other hand, few works have been published using alternative functional omics, which is more suitable to provide a different interpretation of such a relationship. In this work, we pursued a comprehensive metaproteomic investigation on T1D children compared with a group of siblings (SIBL) and a reference control group (CTRL) composed of aged matched healthy subjects, with the aim of finding features in the T1D patients' GM to be related with the onset of the disease. Modulated metaproteins were found either by comparing T1D with CTRL and SIBL or by stratifying T1D by insulin need (IN), as a proxy of ß-cells damage, showing some functional and taxonomic traits of the GM, possibly related to the disease onset at different stages of severity.

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and 1H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.

Exposure to Endocrine Disruptors (Di(2-Ethylhexyl)phthalate (DEHP) and Bisphenol A (BPA)) in Women from Different Residing Areas in Italy: Data from the LIFE PERSUADED Project.

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in south compared to central and northern Italy and for BPA in northern compared to central and southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 µg/kg per day, about 36-fold below the current temporary tolerable daily intake of 4 µg/kg per day established by the EFSA in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. Further, the reduction of exposure to DEHP and BPA, through specific legislative measures, is necessary to limit the harmfulness of these substances.

Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP) in Italian children and adolescents: Data from LIFE PERSUADED project.

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4-14 years old) according to geographical macro-areas and areas, age and sex. Children from the South and the Centre of Italy showed higher median levels of DEHP, as a sum of its metabolites (48.14 and 47.80 µg/L), than those from the North (39.47 µg/L; p = 0.0090 and 0.0004, respectively). Considering the total population, boys are more exposed than girls (only as urinary volume), and children aged 4-6 years have higher median levels than those 7-10 and 11-14 years old. The derived reference values (RV95) for DEHP in children is 168 µg/L. The relative metabolic rates of DEHP, the background levels and, thus, the RV95, vary with the geographical area, age and sex, indicating that all these parameters should be considered in the risk assessment.

Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity. METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2 h post-load glucose concentrations. RESULTS: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p = 0.02). In particular, 124 (20.6%) children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n = 119) satisfying the diagnostic criteria for prediabetes and 0.8% (n = 5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a nearly 2.2-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjustedodds ratio 2.19; 95% CI 1.47-3.29; p <0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjustedodds ratio 1.69, 95% CI 1.06-2.69, p = 0.032), and the PNPLA3 rs738409 polymorphism. Both this PNPLA3 polymorphism and waist circumference were strongly associated with NASH. CONCLUSIONS: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH. LAY SUMMARY: Children with biopsy-proven non-alcoholic fatty liver disease (NAFLD) have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of the progressive form of disease, non-alcoholic steatohepatitis, than those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with non-alcoholic steatohepatitis.

Impact of uteroplacental insufficiency on ovarian follicular pool in the rat.

BACKGROUND: A low oxygen supply to the fetus causes intrauterine growth restriction and can affect gonadal development of the offspring, having a potential impact on fertility. We investigated histology and gene expression in the postnatal rat ovary after fetal hypoxia induced by uterine artery ligation. METHODS: Sprague-Dawley rats underwent uterine artery ligation at day 19 of gestation. Offspring were sacrificed at 5, 20 and 40 days post-partum. Follicles were counted and classified in hematoxylin-eosin stained sections. Gene expression of 90 genes was analyzed by TaqMan® Low Density Array. RESULTS: A significantly lower number of total and primordial follicles was detected in 20 days post-partum intrauterine growth restricted animals. Follicle density was not different at 40 days post-partum, suggesting that compensatory mechanisms occurred during the pre-pubertal window. Uterine artery ligation modified the expression of 24 genes involved in different cellular functions, among which proliferation, apoptosis and metabolism. CONCLUSION: Ovarian follicle pool was affected by fetal hypoxia in early life, but this effect did not persist in puberty. Genes involved in cellular processes were affected at all ages, potentially implying long-term genetic alterations. Further analyses are needed to elucidate later effects of fetal hypoxia on ovarian function and fertility.

Insulin-like growth factor-I and -II levels are associated with the progression of nonalcoholic fatty liver disease in obese children.

OBJECTIVE: To correlate circulating levels of insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein (IGFBP)-3 in a population of obese children with biopsy-proven nonalcoholic fatty liver disease (NAFLD) with clinical, biochemical, and histological features. STUDY DESIGN: We conducted a cross-sectional study at the Hepatometabolic Unit of the Bambino Gesù Children's Hospital, Rome, Italy. Obese children (42 girls and 57 boys) underwent liver biopsy, anthropometry, biochemical assessment, and IGF system evaluation. Serum concentrations of IGF-I, IGF-II, and IGFBP-3 were measured. The liver biopsy features of each case were graded according to the NAFLD Activity Scoring system. The degrees of steatosis, inflammation, ballooning, and fibrosis were calculated. RESULTS: Nonalcoholic steatohepatitis was diagnosed in 14/99 obese subjects. Stepwise regression analysis revealed that IGF-I was the major predictor of ballooning (ß = -0.463; P < .0001) and NAFLD activity score (ß = -0.457; P < .0001), IGF-I/IGFBP-3 ratio was the major predictor of liver inflammation (ß = -0.285; P = .005), and IGF-II was the major predictor of liver fibrosis (ß = 0.343; P < .005). CONCLUSION: Circulating levels of IGF-I and IGF-II are associated with the histological stages of NAFLD and may represent novel markers of liver damage progression in obese children.

Environment, Endocrine Disruptors, and Fatty Liver Disease Associated with Metabolic Dysfunction (MASLD).

Ecological theories suggest that environmental factors significantly influence obesity risk and related syndemic morbidities, including metabolically abnormal obesity associated with nonalcoholic fatty liver disease (MASLD). These factors encompass anthropogenic influences and endocrine-disrupting chemicals (EDCs), synergistically interacting to induce metabolic discrepancies, notably in early life, and disrupt metabolic processes in adulthood. This review focuses on endocrine disruptors affecting a child's MASLD risk, independent of their role as obesogens and thus regardless of their impact on adipogenesis. The liver plays a pivotal role in metabolic and detoxification processes, where various lipophilic endocrine-disrupting molecules accumulate in fatty liver parenchyma, exacerbating inflammation and functioning as new anthropogenics that perpetuate chronic low-grade inflammation, especially insulin resistance, crucial in the pathogenesis of MASLD.

Efficacy and safety of advanced hybrid closed loop systems in children with type 1 diabetes younger than 6 years.

Background: Tight glycemic control is essential for the normal growth and development of preschool children. The aim of our study was to evaluate the impact of advanced hybrid closed loop (AHCL) systems in a real-life setting in children younger than 6 years. Methods: We conducted a two-center prospective study. We enrolled 19 patients with a median age at disease onset of 2.6 years [interquartile range (IQR) 1.6; 4.4] and a median disease duration of 1.4 years (IQR 0.9; 2.8) who were switched to AHCL from multiple daily injections or open-loop insulin therapy and with a 6-month follow-up. Clinical data, sensor glycemic metrics, and pump settings were collected and analyzed. Results: After 6 months of follow-up, there was a significant reduction in median HbA1c (p = 0.0007) and glucose management indicator (p = 0.03). A reduction in both mild (>180 mg/dL) (p = 0.04) and severe (>250 mg/dL) (p = 0.01) hyperglycemia was observed after 1 month of auto mode, and in mild hyperglycemia, it persisted up to 6 months (p = 0.02). A small increase in time below range (<70 mg/dL) was observed (p = 0.04) without a significant difference in time <54 mg/dL (p = 0.73). Time in range increased significantly, reaching a 10% increment (p = 0.03) compared with baseline. A significant reduction in the average sensor glucose was observed (p = 0.01) while coefficient of glucose variability (CV%) remained stable (p = 0.12). No episodes of ketoacidosis or severe hypoglycemia have been recorded. Conclusion: AHCL systems are effective and safe for children younger than 6 years and should be considered as a valid therapeutic option from diabetes onset.

The changing landscape of neonatal diabetes mellitus in Italy between 2003-2022.

CONTEXT: In the last decade Sanger method of DNA sequencing has been replaced by next generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). OBJECTIVE: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) versus 2013-2022 (NGS). METHODS: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM+c.SIR) of the Italian dataset. RESULTS: Fiftyfive patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103,340 (NDM) and 1:1,240,082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, p= 0.034 vs 2003-2012). Notably, five among rare genes were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA), were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes and the individual with lipodystrophy caused by BSCL2 was started on metreleptin. CONCLUSIONS: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and congenital SIR in Italy.

Birth weight influences the clinical phenotype and the metabolic control of patients with type 1 diabetes (T1D).

BACKGROUND: High birth weight has been related to an increased risk of type 1 diabetes (T1D), while suboptimal birth weight (both high and low) has been related to obesity, insulin resistance and type 2 diabetes. Insulin resistance, as a consequence of poor metabolic control, has been described in T1D patients. The aims of the study were to analyse the distribution of birth size for gestational age in a large group of T1D patients and to investigate the effect of birth weight on clinical phenotype. METHODS: Six-hundred two Caucasian T1D patients were evaluated. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weight at <3rd percentile and >97th percentile for gestational age, respectively. Birth weights between the 3rd and 97th percentiles were defined as appropriate for gestational age. The clinical characteristics of small, appropriate for gestational age and large were compared. Multivariable linear regression models were fitted to evaluate the independent effects of birth weight and other covariates (age at T1D onset, gender and T1D duration) on different clinical outcomes (body mass index, HbA(1c), insulin requirement, high-density lipoprotein cholesterol and triglycerides). RESULTS: Thirteen subjects (2.16%) were small (SGA), and 39 (6.48%) were large (LGA). Daily insulin requirement (U/kg/day) was significantly higher in SGA, while body mass index and HbA(1c) were increased in LGA. Multivariable linear regression showed a significant negative effect of birth weight on daily insulin requirement (p < 0.001). CONCLUSIONS: Suboptimal birth weight (both high and low) in T1D patients seems to be associated with clinical characteristics suggestive of insulin resistance.

The Impact of Stress on Health in Childhood and Adolescence in the Era of the COVID-19 Pandemic.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing many challenges to global health. Efforts from the whole scientific community have shed light on the pathogenetic mechanisms and the clinical features of SARS-CoV-2 infection as well as on potential therapeutic strategies. SUMMARY: The consequences of stress related to social isolation and anxiety generated by the pandemic on mental and physical health are collateral effects that are yet poorly investigated.

A critical review of upcoming new therapeutic options in paediatric endocrinology.

Novel and innovative therapeutic options are now available or will soon become available for treating children and adolescents with endocrine disorders and diabetes. Some of these new medicines and procedures have already been proven effective and safe in adults at least in the short term but their use in children is still limited and some efficacy and safety related aspects raise caution especially in the long term. The purpose of this issue is to provide an overview of some of the medicines upcoming to the market, highlighting the advantages and the still existing grey zones.