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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.
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Glucemia , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Sistemas de Infusión de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Masculino , Preescolar , Femenino , Estudios Prospectivos , Glucemia/análisis , Insulina/administración & dosificación , Insulina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Lactante , Control Glucémico/métodos , Estudios de Seguimiento , Automonitorización de la Glucosa Sanguínea/métodos , Resultado del Tratamiento , Hipoglucemia , Hemoglobina Glucada/análisis , NiñoRESUMEN
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.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Sistemas de Infusión de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Estudios Transversales , Niño , Adolescente , Femenino , Masculino , Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Insulina/administración & dosificación , Insulina/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Control Glucémico/métodos , Hemoglobina Glucada/análisis , Estudios de Seguimiento , Pronóstico , Biomarcadores/análisis , Hipoglucemia/prevención & controlRESUMEN
CONTEXT: In the last decade the 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) vs 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: Fifty-five 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 = .034 vs 2003-2012). Notably, among rare genes 5 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. CONCLUSION: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy.
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Diabetes Mellitus , Humanos , Italia/epidemiología , Recién Nacido , Masculino , Femenino , Lactante , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/genética , Pruebas Genéticas/métodos , Resistencia a la Insulina/genética , Mutación , Incidencia , Estudios RetrospectivosRESUMEN
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.
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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.
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Resistencia a la Insulina , Obesidad Mórbida , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Niño , Delgadez , Estudios Transversales , Obesidad , Índice de Masa Corporal , Vitamina B 12 , FenotipoRESUMEN
Introduction Obesity is a worldwide public health problem. Experimental animal and in vitro studies suggest that the exposure to BPA and phthalates are associated to a higher risk of obesity. Objective To determine urinary excretion of bisphenol A and phthalates in obese and normal weight children. Methods A case-control study was conducted in 122 children. Sixty-six obese children 36 girls (mean age 8.41±1.27 years) and 30 boys (mean age 8.51 ± 1.33 years), and 56 normal weight children, 27 girls (mean age 7.64 ± 1.49 years) and 29 boys (mean age 7.77 ± 1.56 years) were studied. Urinary BPA and Bis(2-ethylhexyl) phthalate (DEHP) metabolites (MEHP, MEHHP and MEOHP) were measured respectively by gas chromatography and high-performance liquid chromatography. Individual determinants of exposure were evaluated through "ad hoc" questionnaires. Results BPA and DEHP metabolites were detectable in obese and normal weight children. Obese girls showed significantly higher BPA concentrations in comparison with normal weight girls (means 10.77, 95% CI 7.02-16.53 vs 5.50, 95% CI 3.93-7.71 µg/g creatinine, respectively, p< 0.02). The first step of DEHP metabolic rate was significantly higher in obese girls compared with controls (p<0.05). DEHP metabolites correlated significantly with leptin concentrations in obese girls (p< 0.03). A higher risk of obesity was found in children with BPA levels above the median values with the habit to eat food packaged (OR=11.09, 95% CI=1.28-95.78). Conclusions These findings show that a higher exposure to BPA is associated with the risk of obesity in girls. Further studies are needed to unveil the cause-effect relationship.
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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.
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Hígado Graso , Resistencia a la Insulina , Estado Prediabético , Masculino , Femenino , Humanos , Adolescente , Insulina , Obesidad/metabolismo , Glucosa , Insulina Regular Humana , Glucemia/metabolismoRESUMEN
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.
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Vacunas contra la COVID-19 , COVID-19 , Miocarditis , Niño , Humanos , Masculino , Adulto Joven , Sistemas de Registro de Reacción Adversa a Medicamentos , Vacunas contra la COVID-19/efectos adversos , Miocarditis/etiología , Síndrome , Vacunación/efectos adversos , Vacunas de ARNmRESUMEN
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.
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This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.
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Estatura , Hormona de Crecimiento Humana , Recién Nacido , Adulto Joven , Humanos , Niño , Lactante , Preescolar , Edad Gestacional , Recién Nacido Pequeño para la Edad Gestacional , Hormona de Crecimiento Humana/uso terapéutico , Hormona del CrecimientoRESUMEN
AIM: In the pediatric diabetes clinic, patients with type 1 diabetes mellitus (T1D) account for more than 90% of cases, while monogenic forms represent about 6%. Many monogenic diabetes subtypes may respond to therapies other than insulin and have chronic diabetes complication prognosis that is different from T1D. With the aim of providing a better diagnostic pipeline and a tailored care for patients with monogenic diabetes, we set up a monogenic diabetes clinic (MDC). METHODS: In the first 3 years of activity 97 patients with non-autoimmune forms of hyperglycemia were referred to MDC. Genetic testing was requested for 80 patients and 68 genetic reports were available for review. RESULTS: In 58 subjects hyperglycemia was discovered beyond 1 year of age (Group 1) and in 10 before 1 year of age (Group 2). Genetic variants considered causative of hyperglycemia were identified in 25 and 6 patients of Group 1 and 2, respectively, with a pick up rate of 43.1% (25/58) for Group 1 and 60% (6/10) for Group 2 (global pick-up rate: 45.5%; 31/68). When we considered probands of Group 1 with a parental history of hyperglycemia, 58.3% (21/36) had a positive genetic test for GCK or HNF1A genes, while pick-up rate was 18.1% (4/22) in patients with mute family history for diabetes. Specific treatments for each condition were administered in most cases. CONCLUSION: We conclude that MDC may contribute to provide a better diabetes care in the pediatric setting.
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Complicaciones de la Diabetes , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hiperglucemia , Humanos , Niño , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Pruebas Genéticas , Complicaciones de la Diabetes/genética , Hiperglucemia/genética , MutaciónRESUMEN
BACKGROUND: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. SUMMARY: Different technologies to manipulate drug release have been produced allowing weekly, biweekly, or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. KEY MESSAGES: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of nonphysiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules, and potential novel side effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Adulto , Humanos , Niño , Hormona del Crecimiento , Hormona de Crecimiento Humana/efectos adversos , Enanismo Hipofisario/tratamiento farmacológico , Proteínas Recombinantes/efectos adversosRESUMEN
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.
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COVID-19 , Adolescente , Humanos , SARS-CoV-2 , Pandemias , Ansiedad/epidemiología , Salud GlobalRESUMEN
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.
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Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Islotes Pancreáticos , Microbiota , Humanos , Microbioma Gastrointestinal/fisiología , Diabetes Mellitus Tipo 1/genética , DisbiosisRESUMEN
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.
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Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Células Secretoras de Insulina , Adolescente , Humanos , Niño , Anciano , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , Insulina Regular Humana , InsulinaRESUMEN
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.
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Dietilhexil Ftalato , Disruptores Endocrinos , Ácidos Ftálicos , Adulto , Humanos , Femenino , Exposición a Riesgos Ambientales/análisis , Ácidos Ftálicos/orina , Compuestos de Bencidrilo/análisis , ItaliaRESUMEN
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.