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.

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.

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.

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.

Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital. / 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.

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 debut of 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]: 1.3-3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4-5.2; 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.

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.

Development of an immunoassay for the simultaneous detection of GADA and ZnT8A in autoimmune diabetes using a ZnT8/GAD65 chimeric molecule.

Introduction: The combined presence of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) and to the islet-specific cation efflux transporter ZnT8 (ZnT8A) in serum is the best predictive sign of the loss of immune tolerance and the clinical manifestation of autoimmune diabetes mellitus (DM). The screening of GADA and ZnT8A could help to reach to a correct diagnosis and to start an early and adequate treatment. The aim of the study was to develop an immunoassay for the simultaneous detection of these autoantibodies using a chimera molecule that includes the immunodominant regions of ZnT8 and GAD65, expressed by baculovirus-insect cells system. Materials and Methods: ZnT8/GAD65 was expressed using the Bac to Bac™ baculovirus expression system. The recombinant chimera was purified by an His6-tag and identified by SDS-PAGE and western blot analysis, and by an indirect ELISA using specific antibodies against ZnT8 and GAD65. A fraction of ZnT8/GAD65 was biotinylated. A bridge ELISA (b-ELISA) was developed using ZnT8/GAD65 immobilized in polystyrene microplates, human sera samples from healthy individuals (n = 51) and diabetic patients (n = 49) were then incubated, and afterwards ZnT8/GAD65-biotin was added. Immune complexes were revealed with Streptavidin-Horseradish Peroxidase. Results were calculated as specific absorbance and expressed as standard deviation scores: SDs. Results: ZnT8/GAD65 was efficiently produced, yielding 30 mg/L culture medium, 80% pure. This recombinant chimera retains the immunoreactive conformation of the epitopes that are recognized by their specific antibodies, so it was used for the development of a high sensitivity (75.51%) and specificity (98.04%) b-ELISA for the detection of ZnT8A and/or GADA, in a one-step screening assay. The ROC curves demonstrated that this method had high accuracy to distinguish between samples from healthy individuals and diabetic patients (AUC = 0.9488); the cut-off value was stablished at 2 SDs. Conclusions: This immunoassay is useful either to confirm autoimmune diabetes or for detection in routine screening of individuals at risk of autoimmune DM. As DM is a slow progress disease, remaining asymptomatic for a long preclinical period, serological testing is of importance to establish a preventive treatment.

Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

The rs705708 A allele of the ERBB3 gene is associated with lower prevalence of diabetic retinopathy and arterial hypertension and with improved renal function in type 1 diabetic patients.

INTRODUCTION: The Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in autoimmune processes related to type 1 diabetes mellitus (T1DM) pathogenesis. Accordingly, some studies have suggested that single nucleotide polymorphisms (SNPs) in the ERBB3 gene confer risk for T1DM. Proliferation-associated protein 2G4 (PA2G4) is another candidate gene for this disease because it regulates cell proliferation and adaptive immunity. Moreover, PA2G4 regulates ERBB3. To date, no study has evaluated the association of PA2G4 SNPs and T1DM. AIM: To evaluate the association of ERBB3 rs705708 (G/A) and PA2G4 rs773120 (C/T) SNPs with T1DM and its clinical and laboratory characteristics. METHODS: This case-control study included 976 white subjects from Southern Brazil, categorized into 501 cases with T1DM and 475 non-diabetic controls. The ERBB3 and PA2G4 SNPs were genotyped by allelic discrimination-real-time PCR. RESULTS: ERBB3 rs705708 and PA2G4 rs773120 SNPs were not associated with T1DM considering different inheritance models and also when controlling for covariables. However, T1DM patients carrying the ERBB3 rs705708 A allele developed T1DM at an earlier age vs. G/G patients. Interestingly, in the T1DM group, the rs705708 A allele was associated with lower prevalence of diabetic retinopathy and arterial hypertension as well as with improved renal function (higher estimated glomerular filtration rate and lower urinary albumin excretion levels) compared to G/G patients. CONCLUSIONS: Although no association was observed between the ERBB3 rs705708 and PA2G4 rs773120 SNPs and T1DM, the rs705708 A allele was associated, for the first time in literature, with lower prevalence of diabetic retinopathy and arterial hypertension. Additionally, this SNP was associated with improved renal function.

HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus.

Objective: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.

Mucocutaneous Manifestations in Autoimmune Gastritis: A Prospective Case-Control Study.

INTRODUCTION: Autoimmune gastritis (AIG) is associated with nutritional deficiencies, autoimmune diseases, and gastric malignancies. The aims of the study were to test the hypothesis that mucocutaneous (MC) manifestations occur more often in patients with vs without AIG and to delineate patterns of MC manifestations in AIG. METHODS: A single-center, prospective 2:1 case-control study was conducted. Cases were patients with the diagnosis of AIG based on consistent serologic and histologic findings. Controls had a normal gastric biopsy. MC manifestations were independently evaluated by 3 experienced dermatologists. We conducted a multivariable logistic regression model adjusted for age, sex, Helicobacter pylori, tobacco use, and alcohol consumption to estimate the association between AIG (vs no AIG) and MC manifestations (adjusted odds ratio; 95% confidence interval). RESULTS: We prospectively enrolled 60 cases and 30 controls (mean age 53.5 ± 15.8 vs 53.4 ± 14.5 years; 75% vs 73.3% women). The pooled prevalence of MC immune-mediated diseases was higher in patients with vs without AIG (66.7% vs 23.3%; adjusted odds ratio 12.01 [95% confidence interval: 3.51-41.13]). In patients with AIG, seropositive vs seronegative anti-intrinsic factor antibodies more often had concomitant immunological diseases with MC manifestations (100% vs 58.5%; P = 0.016). The most common MC immune-mediated diseases in AIG were Sjögren syndrome (n = 5, 8.3%), alopecia areata (n = 5, 8.3%), and vitiligo (n = 4, 6.7%). Nutritional deficiency-related MC findings, mainly xerosis, lingual, and nail disorders, were also more common in AIG. DISCUSSION: This is the first comparative study specifically designed to evaluate MC manifestations in AIG. We demonstrated that AIG is more frequently associated with both immune- and nutritional deficiency-related MC manifestations, which might have both diagnostic and therapeutic clinical implications.

Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial.

OBJECTIVES: To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. STUDY DESIGN: By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9 months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. RESULTS: Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs .028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. CONCLUSIONS: It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01735123.

Probabilistic Model of Transition between Categories of Glucose Profiles in Patients with Type 1 Diabetes Using a Compositional Data Analysis Approach.

The time spent in glucose ranges is a common metric in type 1 diabetes (T1D). As the time in one day is finite and limited, Compositional Data (CoDa) analysis is appropriate to deal with times spent in different glucose ranges in one day. This work proposes a CoDa approach applied to glucose profiles obtained from six T1D patients using continuous glucose monitor (CGM). Glucose profiles of 24-h and 6-h duration were categorized according to the relative interpretation of time spent in different glucose ranges, with the objective of presenting a probabilistic model of prediction of category of the next 6-h period based on the category of the previous 24-h period. A discriminant model for determining the category of the 24-h periods was obtained, achieving an average above 94% of correct classification. A probabilistic model of transition between the category of the past 24-h of glucose to the category of the future 6-h period was obtained. Results show that the approach based on CoDa is suitable for the categorization of glucose profiles giving rise to a new analysis tool. This tool could be very helpful for patients, to anticipate the occurrence of potential adverse events or undesirable variability and for physicians to assess patients' outcomes and then tailor their therapies.

Comparison of Clinical Tests for Peripheral Diabetic Neuropathy in a Type 1 Diabetes Cohort.

OBJECTIVE: To examine the performance and agreement of 5 modalities for testing sensory neuropathy against a neurothesiometer among Hispanic patients with type 1 diabetes (T1D) in an outpatient setting. METHODS: A cross-sectional study was conducted at a tertiary reference center in Mexico City. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using a VibraTip device, 128 Hz tuning fork, and the Semmes-Weinstein 5.07/10 g monofilament test, Ipswich touch test (IpTT), and pinprick test (PPT). The VPT obtained using a neurothesiometer was used as the standard. Agreement between tests was calculated using kappa coefficients. RESULTS: Our study included 78 patients (156 examinations), of whom 56.4% were females. The mean age was 38.2 ± 13.0 years, and the mean body mass index was 24.6 ± 4.8 kg/m2. The best sensitivity was found for IpTT and VibraTip (89.7% and 79.3%, respectively), while the PPT and IpTT had the highest positive predictive values (94.4% and 92.9%, respectively). The highest kappa coefficients were obtained for the IpTT vs neurothesiometer (kappa coefficient [κ] = 0.893, P < .001), followed by VibraTip vs neurothesiometer (κ = 0.782, P < .001). The VibraTip vs IpTT also had a substantial agreement (κ= 0.713, P < .001). CONCLUSION: Our findings demonstrated that the IpTT had the best diagnostic performance and agreement compared with the standard in this cohort of Hispanic patients with T1D. The IpTT is a useful, simple test for diabetic neuropathy screening. These findings support its inclusion in future guidelines for diabetic foot examination.

Telemonitoring type 1 diabetes patients during the COVID-19 pandemic in Brazil: was it useful?

ABSTRACT Objectives: To evaluate the performance of telemonitoring in detecting clinical and psychological needs and adherence to the protective measures imposed by the COVID-19 pandemic in addition to providing remote assistance for patients with type 1 diabetes (T1D) in a public university center in Brazil. Subjects and methods: Telemonitoring protocol included phone calls and e-mails. Patients were asked to rate COVID-19-like symptoms, psychological symptoms, epidemiological issues, and adherence to diabetes management (insulin, exercise, and diet) using a 0-to-10 scale. An e-mail address and phone number were offered for further contact if needed. Clinical, demographic, and laboratorial data from the consultations before the pandemic were collected from medical records. Results: Among 321 patients with a previously scheduled consultation over the first 15 weeks of social distancing, 237 (73.8%) could be successfully contacted. Of these, 207 (87.3%) were exclusively evaluated by telemonitoring (190 only by phone or text message and 17 who were also reached by email), and 30 (12.7%) patients attended the consultation for medical reasons detected during the telephone screening. Overall, 44 (18.5%) patients reported COVID-19-like symptoms. One (2.3%) patient was hospitalized and subsequently died. Psychological symptoms were reported by 137 (60.4%) patients and 30 (12.7%) required remote psychological assistance. Appropriate social distancing was performed by 203 (87.9%) patients, and 221 (97.8%) referred use of masks. Conclusions: Telemonitoring T1D patients during the pandemic helped reduce the need for in-person consultations, detect clinical and psychological needs, and offer support to patients in addition to monitoring suspected COVID-19 cases and the adherence to protective measures.

[Type 1 diabetes mellitus and Graves Basedow's disease, a case of Autoimmune Polyglandular Syndrome]. / Diabetes mellitus tipo 1 y enfermedad de Graves Basedow, un caso de Síndrome Poliglandular Autoinmune.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is one of the most frequent autoimmune diseases in childhood. Its diagnosis requires the search for other autoimmune diseases. OBJECTIVE: to present the case of a pediatric patient with two rare concomitant autoimmune endocrine diseases. CLINICAL CASE: A 12-year-old male with no significant morbid history, is hospitalized due to a 3-month clinical pic ture of fatigue, eye pain, intermittent eyelid edema, goiter, polyphagia, polydipsia, polyuria, and weight loss (12 kilograms), compatible with T1DM and Graves-Basedow disease. It was confir med by laboratory tests which showed elevated glycemia (207 mg/dL, HbA1C 10.9%), suppressed TSH (< 0.01 uIU/mL), elevated FT4 (6.99 ng/dL), and the presence of anti-autoantibodies thyroid peroxidase, antithyroglobulin, and anti-TSH receptor, along with suggestive ultrasound findings. Therefore, we established the diagnosis of autoimmune polyglandular syndrome (APS) 3A and initiated treatment with insulin, propranolol, and thiamazole. The patient evolved satisfactorily and was discharged with outpatient follow-up. CONCLUSION: We present the case of an adolescent who presented APS due to T1DM and hyperthyroidism. This APS may be more common than is reported in clinical practice. The alteration of two or more endocrine glands or other autoimmune diseases should make us suspect its diagnosis, with important clinical implications, such as co morbidity and quality of life prognosis.

Worldwide differences in childhood type 1 diabetes: The SWEET experience.

OBJECTIVE: To study worldwide differences in childhood diabetes, comparing relevant indicators among five regions within the SWEET initiative. SUBJECTS: We investigated 26 726 individuals with type 1 diabetes (T1D) from 54 centers in the European region; 7768 individuals from 30 centers in the Asia/Middle East/Africa region; 2642 people from five centers in Australia/New Zealand; 10 839 individuals from seven centers in North America, and 1114 patients from five centers in South America. METHODS: The SWEET database was analyzed based on the following inclusion criteria: T1D, time period 2015-2019, and age < 21 years, with analysis of the most recent documented year of therapy. For the statistical analysis, we used multivariable linear and logistic regression models to adjust for age (<6 years, 6- < 12 years, 12- < 18 years, 18- < 21 years), gender, and duration of diabetes (<2 years, 2- < 5 years, 5- < 10 years, ≥10 years). RESULTS: Adjusted HbA1c means ranged from 7.8% (95%-confidence interval: 7.6-8.1) in Europe to 9.5% (9.2-9.8) in Asia/Middle East/Africa. Mean daily insulin dose ranged from 0.8 units/kg in Europe (0.7-0.8) and Australia/New Zealand (0.6-0.9) to 1.0 unit/kg 0.9-1.1) in Asia/Middle East/Africa. Percentage of pump use was highest in North America (80.7% [79.8-81.6]) and lowest in South America (4.2% [3.2-5.6]). Significant differences between the five regions were also observed with regards to body mass index SD scores, frequency of blood glucose monitoring and presence of severe hypoglycaemia. CONCLUSIONS: We found significant heterogeneity in diabetes care and outcomes across the five regions. The aim of optimal care for each child remains a challenge.

Telemonitoring type 1 diabetes patients during the COVID-19 pandemic in Brazil: was it useful?

OBJECTIVE: To evaluate the performance of telemonitoring in detecting clinical and psychological needs and adherence to the protective measures imposed by the COVID-19 pandemic in addition to providing remote assistance for patients with type 1 diabetes (T1D) in a public university center in Brazil. METHODS: Telemonitoring protocol included phone calls and e-mails. Patients were asked to rate COVID-19-like symptoms, psychological symptoms, epidemiological issues, and adherence to diabetes management (insulin, exercise, and diet) using a 0-to-10 scale. An e-mail address and phone number were offered for further contact if needed. Clinical, demographic, and laboratorial data from the consultations before the pandemic were collected from medical records. RESULTS: Among 321 patients with a previously scheduled consultation over the first 15 weeks of social distancing, 237 (73.8%) could be successfully contacted. Of these, 207 (87.3%) were exclusively evaluated by telemonitoring (190 only by phone or text message and 17 who were also reached by email), and 30 (12.7%) patients attended the consultation for medical reasons detected during the telephone screening. Overall, 44 (18.5%) patients reported COVID-19-like symptoms. One (2.3%) patient was hospitalized and subsequently died. Psychological symptoms were reported by 137 (60.4%) patients and 30 (12.7%) required remote psychological assistance. Appropriate social distancing was performed by 203 (87.9%) patients, and 221 (97.8%) referred use of masks. CONCLUSION: Telemonitoring T1D patients during the pandemic helped reduce the need for in-person consultations, detect clinical and psychological needs, and offer support to patients in addition to monitoring suspected COVID-19 cases and the adherence to protective measures.

Associação entre diabetes mellitus e doenças oculares em pessoas com deficiência visual / Association between diabetes mellitus and eye diseases in people with visual impairment / Asociación entre diabetes mellitus y enfermedades oculares en personas con discapacidad visual

Objetivo: verificar associação entre diabetes mellitus e doenças oculares em pessoas com deficiência visual. Método: estudo transversal com 51 pessoas com diabetes e deficiência visual, em um centro de reabilitação visual do interior paulista, que participaram de entrevista estruturada, em 2018. Utilizou-se os testes: Kolmogorov Smirnov, Regressão de Poisson, Regressão de Logística Binária, e Correlação de Spearman. Resultados: a maioria das pessoas era cega e relatou que a retinopatia diabética, o glaucoma e a catarata foram causa da deficiência visual; com tempo de diagnóstico do diabetes acima de 109 meses. A catarata apresentou um nível de correlação baixa (r=0,280 e p=0,047), e a retinopatia diabética um nível de correlação moderada (r=0,565 e p=0,000), considerando o tempo de diagnóstico do diabetes. Conclusão: associação estatisticamente significante entre o tipo de diabetes e a retinopatia, e correlação estatisticamente significante entre o tempo de diagnóstico do diabetes, a catarata e a retinopatia diabética.

Objective: to verify the association between diabetes mellitus and eye diseases in people with visual impairment. Method: this cross-sectional study involved 51 people with diabetes and visual impairment at a Visual Rehabilitation Center in São Paulo, who participated in a structured interview in 2018. The tests used were: Kolmogorov Smirnov, Poisson Regression, Binary Logistic Regression, and Spearman Correlation. Results: most participants were blind, reported that diabetic retinopathy, glaucoma and cataracts were the causes of their visual impairment, and had been diagnosed with diabetes over 109 months earlier. Cataract returned a low level of correlation with time with diagnosis of diabetes (r = 0.280 and p = 0.047), and diabetic retinopathy, moderate correlation (r = 0.565 and p = 0.000). Conclusion: a statistically significant association was found between type of diabetes and retinopathy, and statistically significant correlations between the time diagnosed with diabetes, cataracts and diabetic retinopathy.

Objetivo: verificar la asociación entre diabetes mellitus y enfermedades oculares en personas con discapacidad visual. Método: este estudio transversal involucró a 51 personas con diabetes y discapacidad visual en un Centro de Rehabilitación Visual en São Paulo, quienes participaron en una entrevista estructurada en 2018.Las pruebas utilizadas fueron: Kolmogorov Smirnov, Regresión de Poisson, Regresión Logística Binaria y Spearman Correlación. Resultados: la mayoría de los participantes eran ciegos, informaron que la retinopatía diabética, el glaucoma y las cataratas eran las causas de su discapacidad visual y habían sido diagnosticados con diabetes más de 109 meses antes. La catarata devolvió un bajo nivel de correlación con el tiempo con el diagnóstico de diabetes (r = 0,280 yp = 0,047) y la retinopatía diabética, correlación moderada (r = 0,565 yp = 0,000). Conclusión: se encontró asociación estadísticamente significativa entre tipo de diabetes y retinopatía, y correlaciones estadísticamente significativas entre el tiempo de diagnóstico de diabetes, cataratas y retinopatía diabética.