Association of sociodemographic and clinical factors with the quality of life of Brazilian individuals with Neurofibromatosis type 1: a cross-sectional study

Abstract Background Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. Objectives This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. Methods This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. Results The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). Study limitations Cross-sectional study, conducted with a convenience sample and using self-reported measures. Conclusions The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.

Diabetes tipo 1 en pediatría durante la pandemia por COVID-19: tiempo de evolución de síntomas y formas de presentación en un centro de referencia / Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital

Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD

Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debutof diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3­3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4­5.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.

Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil.

AIMS: To evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) and its associated factors in Brazilian patients with type 1 diabetes (T1D). METHODS: This cross-sectional, multicentre study was conducted in 14 public clinics in ten Brazilian cities. From 1760 patients, 1712 were included (97.3 %): 953 females (55.7 %), 930 (54.3 %) Caucasians, aged 29.9 ±11.9 years and with diabetes duration of 15.4 ± 9.2 years. CAN was evaluated using cardiovascular autonomic reflex tests. RESULTS: The prevalence of CAN was 23.4 %. Multivariable hierarchical logistic regression showed CAN associated with age, smoking, lower socioeconomic status, higher yearly medical appointments, insulin therapeutic regimens, higher levels of HbA1c, total cholesterol, uric acid, diastolic blood pressure and heart rate, presence of retinopathy, diabetic kidney disease and a tendency to be associated with severe hypoglycemia. Lower health-related quality of life was also found in univariate analysis in these patients. CONCLUSIONS: Patients with T1D presented an important prevalence of CAN that was associated with other diabetes-related chronic complications, and also with demographic, clinical and laboratorial traditional risk factors. Considering lack of formal policy, our data could be used for guiding public health approach to awareness and CAN's screening, diagnosis and clinical management in patients with T1D in Brazil.

[Double diabetes mellitus. Double challenge for the exercise prescription. Systematic review]. / Diabetes mellitus doble. Doble desafío para la prescripción de ejercicio. Revisión sistemática.

Double diabetes (DD) refers to patients with type 1 diabetes who have developed insulin resistance. The objective of this review is to update relevant information on the prescription of physical activity, pharmacological adjustments and consumption of carbohydrates in DD. A systematic search for scientific articles was carried out in the following databases: PubMed, Cochrane, EBSCO, WoS, ScienceDirect and Medline. The evidence analyzed shows that both physical activity (PA) and physical exercise (PE) are essential to achieve metabolic control in people with DD. Physiological considerations such as: insulin adjustments, insulin injection sites, time to perform PA and PE, absolute and relative contraindications are essential to avoid complications, especially hypoglycemia.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Estudio descriptivo de adultos con Diabetes Mellitus Tipo 1: caracterizando una población poco explorada / Descriptive study of adults with type 1 diabetes: characterizing an underexplored population

La diabetes mellitus tipo 1 (DM1) es una enfermedad crónica autoinmune, con una incidencia creciente a nivel mundial. Los avances en el diagnóstico y en el tratamiento de los últimos años prolongaron la esperanza de vida, aumentando así el número de adultos con DM1. Se realizó un corte transversal que incluyó 201 personas adultas con diagnóstico de DM1, afiliados activos a la prepaga institucional de un hospital de alta complejidad de Argentina a Marzo de 2020. Se consignaron las siguientes variables: edad, sexo, comorbilidades, presencia de complicaciones, control glucémico y tratamiento farmacológico. Hubo un porcentaje similar de hombres y mujeres (51,2%), con una mediana de edad de 45 años (IIC 31-59). Un tercio de la población era mayor de 65 años. La mediana de evolución desde el diagnóstico fue de 14,5 años, y la mediana de último valor de hemoglobina glicosilada fue de 7,9%. Entre las complicaciones microvasculares más frecuentes se mencionan pie diabético (18%), retinopatía (6%) y nefropatía (2%). Un 4% presentó enfermedad cardiovascular (infarto agudo de miocardio, enfermedad coronaria, accidente cerebrovascular y/o enfermedad vascular periférica). El 88% recibía tratamiento con esquema intensificado de insulina y 6% usaban infusores de insulina. En relación al tratamiento con antidiabéticos orales, solo 11% recibían metformina, mientras que el uso de otros antidiabéticos orales fue inferior al 4%. En conclusión, este estudio proporciona valiosa información sobre las características de los adultos con DM1, dado que no hay demasiados estudios que aborden esta población (AU)

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease, with an increasing incidence worldwide. Advances in diagnosis and treatment in recent years have extended life expectancy, thus increasing the number of adults with T1DM. A cross-sectional study was conducted, including 201 adult individuals diagnosed with T1DM, active members of the institutional health plan of a high-complexity hospital in Argentina as of March 2020. The following variables were recorded: age, gender, comorbidities, presence of complications, glycemic control, and pharmacological treatment. There was a similar percentage of men and women (51.2%), with a median age of 45 years (IQR 31-59). One-third of the population was over 65 years old. The median duration since diagnosis was 14.5 years, and the median of the last glycated hemoglobin value was 7.9%. Among the most frequent microvascular complications, diabetic foot (18%), retinopathy (6%), and nephropathy (2%) were mentioned. 4% had cardiovascular disease (acute myocardial infarction, coronary artery disease, stroke, and/or peripheral vascular disease). 88% received treatment with intensified insulin regimens, and 6% used insulin pumps. Regarding treatment with oral antidiabetic drugs, only 11% received metformin, while the use of other oral antidiabetic drugs was less than 4%. In conclusion, this study provides valuable information about the characteristics of adults with T1DM, as there are not many studies that address this population (AU)

Glycemic control and study of lipid and bone metabolism in type 1 diabetic children / Control glucémico y estudio del metabolismo lipídico y del óseo en niños con diabetes de tipo 1

Introduction. Type 1 diabetes mellitus is considered one of the most common chronic diseases of childhood. It is a high-risk factor for developing early cardiovascular disease and it also affects bone health. Objective. To describe demographic characteristics and biochemical parameters of a population of children with type 1 diabetes, evaluated in the pediatric diabetes unit of a tertiary Spanish hospital. Materials and methods. In this retrospective study, we determined metabolic, lipid, and bone parameters in 124 children with type 1 diabetes who were monitored in the pediatric diabetes unit of the Hospital Universitario Miguel Servet in Zaragoza (Spain) from May 2020 to July 2021. Results. Children with type 1 diabetes have worse metabolic control of the disease at puberty, but their lipid control is considered acceptable. We found an inverse correlation between bone formation markers and disease duration, as well as with metabolic control. Conclusion. Bone formation markers are inversely correlated with the percentage of glycated hemoglobin and diabetes evolution time. Patients' lipid and bone profiles are more favorable when metabolic control of the disease is achieved.

Introducción. La diabetes mellitus de tipo 1 se considera una de las enfermedades crónicas más frecuentes de la infancia. Es un factor de gran riesgo de desarrollar enfermedad cardiovascular temprana y afecta también la salud ósea. Objetivo. Describir las características demográficas y los parámetros bioquímicos de una población de niños con diabetes de tipo 1, supervisados en la unidad pediátrica de diabetes de un hospital español de tercer nivel. Materiales y métodos. En este estudio retrospectivo, se determinaron los parámetros de control metabólico, lipídico y óseo en 124 niños con diabetes de tipo 1, a los que se hizo seguimiento en la Unidad Pediátrica de Diabetes del Hospital Universitario Miguel Servet de Zaragoza, desde mayo del 2020 hasta julio del 2021. Resultados. Los niños con diabetes de tipo 1 presentan peor control metabólico de la enfermedad en la pubertad, pero su control lipídico se puede considerar aceptable. Existe una correlación inversa de los marcadores de formación ósea con el tiempo de evolución de la enfermedad, así como con el control metabólico. Conclusión. Los marcadores de formación ósea se encuentran correlacionados de forma inversa con el porcentaje de hemoglobina glicosilada y con el tiempo de evolución de la diabetes. En estos pacientes, el perfil lipídico y el óseo son más favorables cuando existe un buen control metabólico de la enfermedad.

Prevalence of latent and overt polyautoimmunity in type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

Effectiveness of Duloxetine versus Other Therapeutic Modalities in Patients with Diabetic Neuropathic Pain: A Systematic Review and Meta-Analysis.

Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study is to analyze the evidence on the efficacy of duloxetine in the management of DPN. Methods: A systematic search in different databases was conducted using the keywords "diabetic neuropathy", "duloxetine therapy", "neuropathic pain", and "Diabetes Mellitus". Finally, eight studies were included in this meta-analysis. Results: All articles comparing duloxetine at different doses vs. a placebo reported significant differences in favor of duloxetine on pain scales like 24 h Average Pain Severity (standardized mean difference [SMD] = -1.06, confidence interval [CI] = -1.09 to -1.03, and p < 0.00001) and BPI Severity (SMD = -0.70, CI = -0.72 to -0.68, and p < 0.00001), among others. A total of 75% of the meta-analyses of studies comparing duloxetine at different doses showed a tendency in favor of the 120 mg/d dose. There were significant differences in favor of duloxetine when compared to routine care on the Euro Quality of Life (SMD = -0.04, CI = -0.04 to -0.03, and p < 0.00001) and SF-36 Survey (SMD = -5.86, CI = -6.28 to -5.44, and p < 0.00001) scales. There were no significant differences on the visual analog scale (VAS) when comparing duloxetine and gabapentin. Conclusions: Duloxetine appears to be effective in the management of DPN in different pain, symptom improvement, and quality of life scales.

Effect of switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL (Gla-300) in Brazilian people with type 1 diabetes.

BACKGROUND: Low adherence to the number of insulin injections and glycemic variability are among the challenges of insulin therapy in type 1 diabetes (T1D). The TOP1 study investigated the effect of switching from twice-daily (BID) basal insulin to once daily (OD) insulin glargine 300 U/mL (Gla-300) on glycemic control and quality of life. METHODS: In this 28-week, phase 4 trial, people with T1D aged ≥ 18 years, who were treated with BID basal insulin in combination with prandial rapid-acting insulin for at least 1 year, and had HbA1c between 7.5% and 10.0%, were switched to Gla-300 OD as basal insulin. The present study aimed to evaluate the impact of this change on HbA1c, glycemic profile, treatment satisfaction and safety. The change in HbA1c from baseline to Week 24 was the primary endpoint. RESULTS: One hundred and twenty-three people with T1D (mean age 37 ± 11 years; 54.5% female) were studied. The disease duration was 20.0 ± 9.8 years, baseline HbA1c and fasting plasma glucose (FPG) were 8.6 ± 0.7% and 201 ± 80.3 mg/dL, respectively. After switching from BID to OD insulin regimen, no significant change in HbA1c was observed from baseline to Week 24 (p = 0.873). There were significant reductions in fasting self-monitoring blood glucose (SMBG) from baseline to Week 24 (175 ± 42 vs. 156 ± 38 mg/dL; p < 0.0001), and in glycemic profile (8-point SMBG) at several time points. There was a significant decrease in the proportion of patients with at least one hypoglycemic event (p = 0.025), in numbers of hypoglycemic events per patient-years of any type (p = 0.036), symptomatic (p = 0.007), and confirmed ≤ 70 mg/dL events (p = 0.049) from run-in to the last 4 weeks on treatment. There were significant improvements in treatment satisfaction (p < 0.0001), perceived hyperglycemia (p < 0.0001) scores and satisfaction with the number of injections between post-run-in and Week 24, and a significant decrease in fear of hypoglycemia. CONCLUSIONS: Switch from BID basal insulin to OD Gla-300 as part of basal bolus therapy in T1D resulted in similar glycemic control as measured by HbA1c, but provided significant improvements in SMBG, daily glucose profile, a lower incidence of hypoglycemia and increased patient satisfaction. TRIAL REGISTRATION: NCT03406000.

Association between HLA alleles and haplotypes with age at diagnosis of type 1 diabetes in an admixed Brazilian population: A nationwide study.

To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6-<11 years, ≥11-<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self-reported colour-race and identified a familiar history of T1D in first-degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub-Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as HLA-DQB1*03:02g, -DQA1*03:01g, -02:01g, DRB1*04:05g and -04:02g were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as DRB1*07:01g, -13:03g, DQB1*06:02g and DQA1*02:01 were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self-reported colour-race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype DRB1*03:01g~DQA1*05:01g~DQB1*02:01g did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high-risk haplotype DRB1*04:05~DQA1*03:01~DQB1*03:02 was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles DQA1*01:02g, DQB1*06:02g, DRB1*07:01g and DRB1*13:03g and haplotypes DRB1*13:03g~DQA1*05:01g~DQB1*03:01g and DRB1*16:02g~DQA1*01:02g~DQB1*05:02g were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well-known genomic risk or protection factors for T1D.

Consenso mexicano de tirosinemia tipo 1

INTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.

INTRODUCCIÓN: La tirosinemia tipo 1 es una enfermedad rara, con herencia autosómica recesiva, con múltiples manifestaciones clínicas, que pueden comprender desde falla hepática aguda neonatal, síndrome colestásico neonatal, hepatitis crónica, cirrosis o hepatocarcinoma, hasta alteraciones renales como acidosis tubular renal, síndrome de Fanconi o raquitismo hipofosfatémico, entre otras. El diagnóstico se basa en la presencia de metabolitos tóxicos en la sangre y la orina, idealmente con la confirmación molecular de la enfermedad. MÉTODO: Se realizó un consenso con expertos en el área de los errores innatos del metabolismo (EIM): ocho gastroenterólogos pediatras, dos médicos especialistas en EIM, dos genetistas, tres nutriólogas pediatras especializadas en EIM y un cirujano pediatra especialista en trasplantes. Se formaron seis mesas de trabajo encargadas de desarrollar los enunciados con sus justificaciones y fueron votados anónimamente 32 enunciados en una escala Likert con un método Delphi. La primera votación fue virtual, obteniendo consenso del 80% de los enunciados, y la segunda fue presencial, obteniendo el 20% restante. RESULTADOS: Los enunciados fueron divididos en epidemiología, cuadro clínico, diagnóstico, tratamiento nutricional y médico, y consejo genético. CONCLUSIONES: Este consenso constituye una valiosa herramienta para los médicos de atención primaria, pediatras y gastroenterólogos pediátricos, ya que ayuda a diagnosticar y tratar rápidamente esta enfermedad. Su impacto en la morbilidad y mortalidad de los pacientes con tirosinemia tipo 1 es sustancial.

Metabolic Changes Induced by Bariatric Surgery May be Mediated by PAI-1 and PCSK9 Crosstalk.

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Involving different stakeholders in prioritising outcomes to assess healthcare systems response for type 1 diabetes management: Using co-creation approaches in Peru.

BACKGROUND: Engaging diverse stakeholders in developing core outcome sets (COSs) can produce more meaningful metrics as well as research responsive to patient needs. The most common COS prioritisation method, Delphi surveys, has limitations related to selection bias and participant understanding, while qualitative methods like group discussions are less frequently used. This study aims to test a co-creation approach to COS development for type 1 diabetes (T1DM) in Peru. METHODS: Using a co-creation approach, we aimed to prioritise outcomes for T1DM management in Peru, incorporating perspectives from people with T1DM, caregivers, healthcare professionals, and decision-makers. A set of outcomes were previously identified through a systematic review and qualitative evidence synthesis. Through qualitative descriptive methods, including in-person workshops, each group of stakeholders contributed to the ranking of outcomes. Decision-makers also discussed the feasibility of measuring these outcomes within the Peruvian healthcare system. RESULTS: While priorities varied among participant groups, all underscored the significance of monitoring healthcare system functionality over mortality. Participants recognized the interconnected nature of healthcare system performance, clinical outcomes, self-management, and quality of life. When combining the rankings from all the groups, metrics related to economic impact on the individual and structural support, policies promoting health, and protecting those living with T1DM were deemed more important in comparison to measuring clinical outcomes. CONCLUSION: We present the first COS for T1DM focused on low-and-middle-income countries and show aspects of care that are relevant in this setting. Diverse prioritisation among participant groups underscores the need of inclusive decision-making processes. By incorporating varied perspectives, healthcare systems can better address patient needs and enhance overall care quality.

The osmoregulated metabolism of trehalose contributes to production of type 1 fimbriae and bladder colonization by extraintestinal Escherichia coli strain BEN2908.

In Escherichia coli, the disaccharide trehalose can be metabolized as a carbon source or be accumulated as an osmoprotectant under osmotic stress. In hypertonic environments, E. coli accumulates trehalose in the cell by synthesis from glucose mediated by the cytosolic enzymes OtsA and OtsB. Trehalose in the periplasm can be hydrolyzed into glucose by the periplasmic trehalase TreA. We have previously shown that a treA mutant of extraintestinal E. coli strain BEN2908 displayed increased resistance to osmotic stress by 0.6 M urea, and reduced production of type 1 fimbriae, reduced invasion of avian fibroblasts, and decreased bladder colonization in a murine model of urinary tract infection. Since loss of TreA likely results in higher periplasmic trehalose concentrations, we wondered if deletion of otsA and otsB genes, which would lead to decreased internal trehalose concentrations, would reduce resistance to stress by 0.6 M urea and promote type 1 fimbriae production. The BEN2908ΔotsBA mutant was sensitive to osmotic stress by urea, but displayed an even more pronounced reduction in production of type 1 fimbriae, with the consequent reduction in adhesion/invasion of avian fibroblasts and reduced bladder colonization in the murine urinary tract. The BEN2908ΔtreAotsBA mutant also showed a reduction in production of type 1 fimbriae, but in contrast to the ΔotsBA mutant, resisted better than the wild type in the presence of urea. We hypothesize that, in BEN2908, resistance to stress by urea would depend on the levels of periplasmic trehalose, but type 1 fimbriae production would be influenced by the levels of cytosolic trehalose.

Association between perinatal and obstetric factors and early age at diagnosis of type 1 diabetes mellitus: a cohort study.

OBJECTIVES: To evaluate the association between perinatal and obstetric factors as potential triggers for the early onset of T1DM. METHODS: This was a retrospective cohort study enrolling 409 patients diagnosed with T1DM, in Bauru, São Paulo, Brazil, from 1981 to 2023. Data were retrieved from medical records, regarding sociodemographic parameters as age, sex, ethnicity, and socioeconomic status. Perinatal and obstetric factors as delivery type, gestational age, filiation order, length of exclusive breastfeeding, maternal age, maternal and fetal blood types, and occurrence of maternal gestational diabetes were also analyzed. An adapted survival analysis was employed to gauge the impact of each assessed variable at the age of T1DM diagnosis. RESULTS: The median age of T1DM diagnosis was 10.3 years with an interquartile range between 6.4 and 15.5 years. Delivery type and filiation order were the only factors statistically significantly associated with an early age at T1DM diagnosis. Patients who were born through cesarean section and who were firstborns showed a 28.6 and 18.0 % lower age at T1DM diagnosis, respectively, compared to those born through vaginal delivery and those that were nonfirstborns. CONCLUSIONS: Being born by cesarean section and being firstborn showed to be statistically significant factors to determine an early T1DM diagnosis.

Factor Associated with Adherence to the Protein and Fat Counting Strategy by Adults with Type 1 Diabetes Mellitus.

Carbohydrate counting is one of the dietary strategies used for the management of type 1 diabetes (T1DM), and counting proteins and fats allows individuals to achieve better glycemic and metabolic control, reducing glycemic variability and long-term complications. The aim of this paper is to analyze the factors associated with adherence to the protein- and fat-counting strategy in adults with T1DM. This cross-sectional study was conducted from November 2021 to June 2022 through an online questionnaire. We applied Pearson's Chi-square test with adjusted residual analysis and a binomial logistic regression test using SPSS software, version 24.0, considering p < 0.05 as indicative of statistical significance. There was an association between performing protein and lipid counting and having a higher education level, income exceeding three minimum wages, and having adequate glycated hemoglobin. Performing protein and lipid counting increased the chances of having adequate HbA1c by 4.3 times. Protein and lipid counting was a predictor of having adequate HbA1c. The results suggest that considering the practice of counting proteins and fats is important as a strategy to optimize glycemic control.

A pilot study of mitochondrial genomic ancestry in admixed Brazilian patients with type 1 diabetes.

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country's colonization history.