Prolonged Remission Induced by FENofibrate in children with newly diagnosed type 1 diabetes (PRIFEN): protocol of a randomised controlled trial.

INTRODUCTION: Sphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. METHODS AND ANALYSIS: A total of 102 children aged 10-17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. TRIAL REGISTRATION NUMBER: EnduraCT 2020-003916-28.

Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes.

BACKGROUND/AIM: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. METHODS: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow-up strategies. RESULTS: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3-monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. CONCLUSIONS: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings.

Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes: a secondary analysis of the POInT Study.

BACKGROUND: Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines. METHODS: In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing ß-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8). The protocol actively promotes vitamin D sufficiency to optimise immune tolerance. VDI was defined as a concentration below 30 ng/mL and was treated according to local guidelines of participating centres. Recovery from VDI was defined as a concentration above or equal to 30 ng/mL on the subsequent visit after VDI. RESULTS: 1050 infants were included, of which 5937 vitamin D levels were available for analyses. VDI was observed in 1464 (24.7%) visits and 507 (46.1%) of these were not resolved at the next visit. The risk of having VDI was independently associated with season (higher in winter), weight (higher with increased weight), age (higher with increased age) and country (higher in England). The risk of not recovering from VDI was independently associated with the season of the previously determined VDI, which was higher if VDI was identified in winter. CONCLUSIONS: VDI is frequent in infants with increased risk of developing T1D. Treatment guidelines for VDI do not seem effective. Increasing supplementation dosages in this patient population seems warranted, especially during winter, and increasing dosages more aggressively after VDI should be considered.

Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity. METHODS: Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk. RESULTS: The COVID-19 pandemic was associated with increased time-varying BMI (ß = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (ß = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (ß = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (ß = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (ß = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively). CONCLUSIONS/INTERPRETATION: Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.

Super Bolus-A Remedy for a High Glycemic Index Meal in Children with Type 1 Diabetes on Insulin Pump Therapy?-A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: This study aimed to compare whether a super bolus (SB) is a more efficient strategy than a normal bolus (NB) for high glycemic index (h-GI) meals in children with type 1 diabetes (T1D). METHODS: A randomized, double-blind, crossover trial with an allocation ratio of 1:1, registered at ClinicalTrials.gov (NCT04019821). 72 children aged 10-18 years with T1D > 1 year, and on insulin pump therapy > 3 months were included. As an intervention, they ate a h-GI breakfast for the two following days and receive a prandial insulin bolus either in the form of SB or NB. RESULTS: The SB group had lower glucose values during the observation time and lower glucose levels in 90th min (primary end point). The median time in range was also higher after SB. At the same time, more hypoglycemic episodes and a higher time below range were noted in this group. Almost 90% of them were the threshold value for initiating treatment for hypoglycemia and occurred near the end of observation period. More hyperglycemic episodes and over twice as much time in hyperglycemia were noted after NB. CONCLUSIONS: Super bolus is an effective strategy to avoid postprandial hyperglycemia but the basal insulin suspension should be longer to avoid hypoglycemia (f.ex. 3 h).

Teplizumab and ß-Cell Function in Newly Diagnosed Type 1 Diabetes.

BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown. METHODS: In this phase 3, randomized, placebo-controlled trial, we assessed ß-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in ß-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events. RESULTS: Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. CONCLUSIONS: Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of ß-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729.).

SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood.

Importance: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends. Objective: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood. Design, Setting, and Participants: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022. Exposure: SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022. Main Outcomes and Measures: The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed. Results: Consent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (<18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009). Conclusion and relevance: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.

Pure-protein load for children with type 1 diabetes: is any additional insulin needed? A randomized controlled study.

AIMS: Study in adults with T1D showed that delivery of insulin for pure-protein meals may not be obligatory. The aim of this study was to assess the effects of whey isolate protein drink consisting of 50 g/200 kcal from pure protein on postprandial glycemia (PPG) following with square-wave insulin bolus in comparison with no insulin strategy in T1D children on insulin pumps. METHODS: This was a randomized, double-blind, cross-over study including 58 children with mean: age 14.62 ± 3.64 years. Participants were randomly assigned into two treatment orders: NB-SQ (no bolus on the first day) and SQ-NB (square-bolus on the first day). The primary outcome was PPG during a 5-h follow-up. The secondary outcome was the frequency of hypoglycemia and glycemic variability parameters. RESULTS: PPG [mg/dl] since 150 min of the follow-up was significantly lower when square-wave bolus was delivered (group SQ vs NB); at 150, 180, 210, 240, 270, 300 min: 130.6 versus 154.5 (p = 0.009), 153.4 versus 124.9 (p = 0.004), 151.0 versus 118.7 (p = 0.003), 146.4 versus 114.2 (p = 0.002), 141.2 versus 107.7 (p = 0.001), 131.0 versus 105.1 (p = 0.005). We observed statistically significant difference in overall rate of hypoglycemia < 70 mg/dl between groups SQ versus NB: 6.8% versus 2.5% (p = 0.001). The overall rate of hypoglycemia below 54 mg/dl was < 1% (p = 0.452). CONCLUSIONS: A meal containing 50 g of pure protein may be consumed without additional insulin dose. An additional square-wave bolus may be beneficial in reducing PPG. To avoid hypoglycemia, lower insulin dose should be calculated for 100 kcal from protein than for individual insulin-to-carb ratio.

The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study.

INTRODUCTION: This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. METHODS: Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several time points during an intervention study (POInT-study), where oral insulin was administered daily. RESULTS: Data were collected from 2595 parents of 1371 children across five countries. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. When thinking about their child's risk for developing T1D (disease-specific anxiety), 47.2% worried, felt nervous and tense. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. CONCLUSION: Overall, symptoms of depression and panic-related anxiety are comparable with the German population. When asked about their child's risk for T1D during the intervention study, some parents reported disease-specific anxiety, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team.

Elevations in blood glucose before and after the appearance of islet autoantibodies in children.

The etiology of type 1 diabetes has polygenic and environmental determinants that lead to autoimmune responses against pancreatic ß cells and promote ß cell death. The autoimmunity is considered silent without metabolic consequences until late preclinical stages,and it remains unknown how early in the disease process the pancreatic ß cell is compromised. To address this, we investigated preprandial nonfasting and postprandial blood glucose concentrations and islet autoantibody development in 1,050 children with high genetic risk of type 1 diabetes. Pre- and postprandial blood glucose decreased between 4 and 18 months of age and gradually increased until the final measurements at 3.6 years of age. Determinants of blood glucose trajectories in the first year of life included sex, body mass index, glucose-related genetic risk scores, and the type 1 diabetes-susceptible INS gene. Children who developed islet autoantibodies had early elevations in blood glucose concentrations. A sharp and sustained rise in postprandial blood glucose was observed at around 2 months prior to autoantibody seroconversion, with further increases in postprandial and, subsequently, preprandial values after seroconversion. These findings show heterogeneity in blood glucose control in infancy and early childhood and suggest that islet autoimmunity is concurrent or subsequent to insults on the pancreatic islets.

Seasonally Dependent Change of the Number of Fractures after 50 Years of Age in Poland-Analysis of Combined Health Care and Climate Datasets.

Aim: The incidence of fractures correlates with many independent and interrelated factors. The aim of the study was to examine trends in fracture incidence and to find possible reasons for changes. Materials and methods: A complete dataset of Polish population aged above 50 from the National Heath Fund­which is a single, state-owned payer for the health service procedures in Poland­covering the years between 2010 and 2015 was analyzed along with climate dataset. Results: The analysis indicated that there was a substantial and statistically significant decrease in the incidence of forearm and hip fractures (p = 0.007 and 0.007, respectively). On the other side, there was a statistically significant increase in incidence of humerus and lumbar fractures (p = 0.002, p < 0.001, respectively). The observed changes (especially decrease in forearm and hip fracture incidence) happened mostly in the cold season and were correlated to mean-temperature changes during the assessed time period. Conclusion: In the analysis based on the dataset obtained from fracture-related database collected in Poland in the years 2010−2015 in the population of patients over 50 years of age, we observed that the changes of fracture incidence during the observation period are associated with and may be dependent on the season (warmer versus colder) and on mean temperature increase during the observation period.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

Super Bolus: a remedy for a high glycemic index meal in children with type 1 diabetes on insulin pump therapy?-study protocol for a randomized controlled trial.

BACKGROUND: Postprandial hyperglycemia (PPH) is a common clinical problem among patients with type 1 diabetes (T1D), which is related to high glycemic index (h-GI) meals. The main problem is linked to high, sharp glycemic spikes following hypoglycemia after h-GI meal consumption. There is a lack of effective and satisfactory solutions for insulin dose adjustment to cover an h-GI meal. The goal of this research was to determine whether a Super Bolus is an effective strategy to prevent PPH and late hypoglycemia after an h-GI meal compared to a Normal Bolus. METHODS: A total of 72 children aged 10-18 years with T1D for at least 1 year and treated with continuous subcutaneous insulin infusion for more than 3 months will be enrolled in a double-blind, randomized, crossover clinical trial. The participants will eat a h-GI breakfast for the two following days and receive a prandial insulin bolus in the form of a Super Bolus 1 day and a Normal Bolus the next day. The glucose level 90 min after the administration of the prandial bolus will be the primary outcome measure. The secondary endpoints will refer to the glucose levels at 30, 60, 120, 150, and 180 min postprandially, the area under the blood glucose curve within 180 min postprandially, peak glucose level and the time to peak glucose level, glycemic rise, the mean amplitude of glycemic excursions, and the number of hypoglycemia episodes. DISCUSSION: There are still few known clinical studies on this type of bolus. A Super Bolus is defined as a 50% increase in prandial insulin dose compared to the dose calculated based on the individualized patient's insulin-carbohydrate ratio and a simultaneous suspension of basal insulin for 2 h. Our patients reported the best experience with such a combination. A comprehensive and effective solution to this frequent clinical difficulty of PPH after an h-GI meal has not yet been found. The problem is known and important, and the presented solution is innovative and easy to apply in everyday life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019821.

Sensitivity to Sweet and Salty Tastes in Children and Adolescents with Type 1 Diabetes.

Taste function impairment is observed in people with type 1 diabetes (T1D). It is most often related to sweet taste. It is associated with such factors as diabetic neuropathy, smoking, age, duration of the disease and a rigorous diet that eliminates easily digestible carbohydrates. The aim of the study was to compare sensitivity to sweet and salty tastes between healthy children and adolescents and children and adolescents with T1D. The study group consisted of children with T1D (n = 35), with at least 5 years of disease history, while the group of healthy children included 46 individuals selected in terms of age, gender and BMI. A study concerning the perception of sweet and salty taste was carried out with the use of the specific gustometry method (examining the recognition and assessment of the intensity of taste sensations, performing a hedonic assessment). Children and adolescents from both groups had trouble recognising tastes. Children and adolescents with T1D were more likely to recognise sweet taste correctly even at its lower concentrations compared to healthy individuals (p = 0.04). Salty taste was significantly more often correctly identified by healthy children compared to T1D patients (p = 0.01). Children and adolescents with T1D reported a stronger intensity of perceived tastes than healthy ones. No significant differences in perceived pleasure were noted at lower sucrose concentrations in any group. The intensity score was higher in individuals with T1D at higher sucrose concentrations. No significant differences occurred in the assessment of salty taste intensity. The hedonic scoring of solutions with higher concentrations of sweet taste was higher in people with T1D than in healthy ones, while salty taste was assessed neutrally. Children and adolescents with T1D were demonstrated to have some taste recognition disorders. Therefore, monitoring taste function in pediatric diabetic clinical practice seems relevant, as it may be associated with important implications for the intake of a particular type of food and for the development of eating habits and preferences.

Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol.

INTRODUCTION: The Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood. METHODS AND ANALYSIS: Infants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin. ETHICS AND DISSEMINATION: The study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study. TRIAL REGISTRATION NUMBER: NCT04769037.

Continuous glucose monitoring systems in well-controlled children with type 1 diabetes mellitus.

INTRODUCTION: Numerous studies have demonstrated the clinical benefits of using continuous glucose monitoring (CGM) systems among patients with type 1 diabetes (T1D). Aim of the study was to assess the effectiveness of CGM on metabolic control in children with T1D and well-controlled disease prior to the study. MATERIAL AND METHODS: This prospective analysis included 99 children (46 girls) at the median age of 11.23 years and diabetes duration of at least 1 year (median: 5.16 years), generally well controlled metabolically (median HbA1c: 7.0%), and treated with continuous subcutaneous insulin infusion (CSII). The patients had used CGM for at least 150 days. We analysed the participants in subgroups based on baseline HbA1c < 7%, ≥ 7%, age, and sex. RESULTS: Children with baseline HbA1c < 7% were characterized by significantly increased HbA1c after the median of 273 days (217; 320) of CGM usage (6.3% vs. 6.6%, respectively; p = 0.002). No significant change in HbA1c was noted in children with baseline HbA1c ≥ 7% (7.5% vs. 7.4%, respectively; p = 0.191), but 20% of the group reached the target of HbA1c < 7.0%. The analysis of CGM data revealed that no group achieved the CGM targets of good metabolic control. Total daily insulin requirements remained stable in both groups (p = 0.752; p = 0.274), but the amount of basal insulin increased statistically in both groups (p = 0.009; p ≤ 0.001). CONCLUSIONS: The application of CGM provides detailed information concerning glycaemic control and is beneficial in some, but not all, T1D children with good diabetes control.

The incidence rate of hospitalized lysosomal storage diseases in Poland in 2013-2015 based on data from the National Health Fund.

INTRODUCTION: The reported data address the incidence of lysosomal storage diseases, obtained from the public health service databases in Poland. Data are given by subtypes from the National Health Fund between 2013 and 2015. MATERIAL AND METHODS: Patients with lysosomal storage diseases were identified in the National Health Fund database (2013-2015). In order to ensure that the reported incidence data included only new patients. The geographic area of residence in 2013-2015 was divided into 6 parts. RESULTS: The incidence rate of lysosomal storage diseases in Poland is about 1.84/1 million/person/years. Other sphingolipidosis was the largest disease category, with 127 patients (incidence 1.1 patients/million habitants), follow by GM2 gangliosidosis - 29 patients (incidence 0.25 patients/million habitants). Men had a somewhat higher incidence than women (respectively IR = 2.53, IR = 1.84). The number of deaths with lysosomal storage disease patients hospitalized between the years 2013 through 2015 is higher in young people (0-9 years old). CONCLUSIONS: The incidence rate of lysosomal storage diseases in Poland is about 1.84 per million person-years. Other sphingolipidosis was the largest disease category, followed by GM2 gangliosidosis. The hospitalization rate of lysosomal storage diseases was higher in men.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.