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.).

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.

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.

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.

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.

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.

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.

Influence of two different methods of nutrition education on the quality of life in children and adolescents with type 1 diabetes mellitus - a randomized study.

Background. Nutrition education is one of the most important factors determining the effectiveness of treatment and maintaining an adequate quality of life (QoL) in children and adolescents with type 1 diabetes.Material and Methods. A randomized single-blind study was conducted between October 2017 and April 2019 at the Children's Clinical Hospital in Warsaw. The study included 170 patients (aged 8-17) with at least 1-year history of type 1 diabetes, treated with insulin pumps. The participants were randomly divided into two groups: a control group (C) - traditional/ informative education methods, and an experimental group (E) - modern/interactive methods. PedsQL Diabetes Module 3.0 questionnaire was used in the assessment of the QoL. Total PedsQL score was the primary outcome. The secondary outcomes included the results obtained in five subscales of the questionnaire. The relationships between selected variables and changes in scores were also verified.Results. Data obtained from 136 patients were analyzed. In both groups no significant changes regarding total PedsQL were noted 6 months after the intervention. However, a significant reduction occurred as regards the scores of 'Communication' subscale in group C. Analyzing other determinants of the QoL, significant dependencies were observed between: the level of physical activity and a change in 'Diabetes symptoms' subscale, and the level of parents' education and a change in 'Treatment barriers' subscale.Conclusions. Both methods of nutrition education exerted a comparable influence on the total QoL. However, modern methods were more effective in terms of the improvement in the aspect of communication. Additionally, moderate physical activity and parents' tertiary education constituted valid determinants of various aspects of the QoL in children and adolescents with type 1 diabetes.

Physiological factors influencing diabetes control in type 1 diabetes children with insulin pumps from diagnosis.

BACKGROUND: The aim of this study was to identify the physiological factors influencing diabetes control in children with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) from diabetes diagnosis. METHODS: This study focused on 163 children (81 boys) initiated with CSII within 2 weeks after T1D recognition and treated for at least 3 years. We analysed fasting C-peptide, GADA, ICA, IA2A, BMI z-score, total daily dose, and basal insulin. Patients were divided into groups according to their metabolic control: 7.5% > HbA1c ≥ 7.5% at the end of the study. RESULTS: At the end of the follow-up, patients with HbA1c <7.5%, had a lower HbA1c level at diagnosis (11.7% vs 12.6%; P = 0.018), lower HbA1c level at both the first-year (6.7% vs 7.3%; P = 0.000) and the second-year (6.8% vs.7.7%; P = 0.000) follow-up, and a lower GADA level (P = 0.001). A multiple logistic regression analysis showed that HbA1c at diagnosis (P = 0.012), HbA1c at first year (P = 0.000), HbA1c at second year (P = 0.000), age at diagnosis (P = 0.047), GADA (P = 0.031), and basal insulin at third year (P = 0.032), influenced HbA1c <7.5% at the third year of follow-up. At the end of the study, 76% of patients started with CSII at the age <10 years and 49% of subjects initiated with CSII at the age ≥10 years achieved HbA1c ≤7.5%. CONCLUSIONS: This study shows that for those who initiated CSII at T1D onset, younger age, less intense autoimmune process, a low HbA1c at recognition, and good diabetes control during the first year of treatment were associated with long-term optimal glycaemic control.

Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective.

BACKGROUND: Frequent use of modern diabetes technologies increases the chance for optimal type 1 diabetes (T1D) control. Limited reimbursement influences the access of patients with T1D to these modalities and could worsen their prognosis. We aimed to describe the situation of reimbursement for insulins, glucometers, insulin pumps (CSII) and continuous glucose monitoring (CGM) for children with T1D in European countries participating in the SWEET Project and to compare data from EU countries with data from our previous study in 2009. METHODS: The study was conducted between March 2017 and August 2017. First, we approached diabetes technology companies with a survey to map the reimbursement of insulins and diabetic devices. The data collected from these companies were then validated by members of the SWEET consortium. RESULTS: We collected data from 29 European countries, whereas all types of insulins are mostly fully covered, heterogeneity was observed regarding the reimbursement of strips for glucometers (from 90 strips/month to no limit). CSII is readily available in 20 of 29 countries. Seven countries reported significant quota issues or obstacles for CSII prescription, and two countries had no CSII reimbursement. CGM is at least partially reimbursed in 17 of 29 countries. The comparison with the 2009 study showed an increasing availability of CSII and CGM across the EU. CONCLUSIONS: Although innovative diabetes technology is available, a large proportion of children with T1D still do not benefit from it due to its limited reimbursement.

Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials-GPPAD-02 study design and first results.

Primary prevention of type 1 diabetes (T1D) requires intervention in genetically at-risk infants. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, that identifies infants with a genetic high risk of T1D, enrolls these into primary prevention trials, and follows the children for beta-cell autoantibodies and diabetes. Genetic testing is offered either at delivery, together with the regular newborn testing, or at a newborn health care visits before the age of 5 months in regions of Germany (Bavaria, Saxony, Lower Saxony), UK (Oxford), Poland (Warsaw), Belgium (Leuven), and Sweden (Region Skåne). Seven clinical centers will screen around 330 000 infants. Using a genetic score based on 46 T1D susceptibility single-nucleotide polymorphisms (SNPs) or three SNPS and a first-degree family history for T1D, infants with a high (>10%) genetic risk for developing multiple beta-cell autoantibodies by the age of 6 years are identified. Screening from October 2017 to December 2018 was performed in 50 669 infants. The prevalence of high genetic risk for T1D in these infants was 1.1%. Infants with high genetic risk for T1D are followed up and offered to participate in a randomized controlled trial aiming to prevent beta-cell autoimmunity and T1D by tolerance induction with oral insulin. The GPPAD-02 study provides a unique path to primary prevention of beta-cell autoimmunity in the general population. The eventual benefit to the community, if successful, will be a reduction in the number of children developing beta-cell autoimmunity and T1D.

Assessment of Safety and Glycemic Control During Football Tournament in Children and Adolescents With Type 1 Diabetes-Results of GoalDiab Study.

PURPOSE: To assess glycemic control and safety of children and adolescents with type 1 diabetes participating in a 2-day football tournament. METHODS: In total, 189 children with type 1 diabetes from 11 diabetes care centers, in Poland, participated in a football tournament in 3 age categories: 7-9 (21.2%), 10-13 (42.9%), and 14-17 (36%) years. Participants were qualified and organized in 23 football teams, played 4 to 6 matches of 30 minutes, and were supervised by a medical team. Data on insulin dose and glycemia were downloaded from personal pumps, glucose meters, continuous glucose monitoring, and flash glucose monitoring systems. RESULTS: The median level of blood glucose before the matches was 6.78 (4.89-9.39) mmol/L, and after the matches, it was 7.39 (5.5-9.87) mmol/L (P = .001). There were no episodes of severe hypoglycemia or ketoacidosis. The number of episodes of low glucose value (blood glucose ≤3.9 mmol/L) was higher during the tournament versus 30 days before: 1.2 (0-1.5) versus 0.7 (0.3-1.1) event/person/day, P < .001. Lactate levels increased during the matches (2.2 [1.6-4.0] mmol/L to 4.4 [2.6-8.5] mmol/L after the matches, P < .001). CONCLUSIONS: Large football tournaments can be organized safely for children with type 1 diabetes. For the majority of children, moderate mixed aerobic-anaerobic effort did not adversely affect glycemic results and metabolic safety.

Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland. METHODS: In this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland. RESULTS: Overall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17-year-olds. In the urban population (age 0-17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas. CONCLUSIONS: The incidence of T1D in children living in eastern and central Poland increased 1.5-fold over the 5-year observation period with the highest rise in 10 to 14-year-olds and significantly higher rates in urban children compared with their peers living in rural areas.

The additional dose of insulin for high-protein mixed meal provides better glycemic control in children with type 1 diabetes on insulin pumps: randomized cross-over study.

BACKGROUND: Delivery of insulin for high-protein low-fat meals with carbohydrates on the basis of carbohydrates leads to higher late postprandial glycemia. Studies with mixed meals demonstrated lower blood glucose level after dual wave bolus. The objective of our study was to assess the impact of additional dose of insulin in dual wave bolus for high-protein mixed meal on the postprandial glycemia. MATERIALS AND METHODS: We performed a randomized, double-blind, two-way cross-over study, including 58 children with type 1 diabetes, aged 14.7 ± 2.2 years. Participants were randomly assigned into two treatment orders: NORMAL-DUAL or DUAL-NORMAL BOLUS. They consumed standardized high-protein, low-fat meals with carbohydrates. The primary outcome was postprandial glycemia (PPG) based on capillary blood glucose measurements (CBGM). The secondary outcomes were the frequency of hypoglycemia, area under glucose curve, mean amplitude of glycemic excursion (MAGE) and glycemic rise. RESULTS: PPG assessed at 180 min was significantly lower when dual wave bolus was delivered (NORMAL 162 mg/dL [9 mmol/L] vs DUAL 130.0 mg/dL [7.22 mmol/L]; P = .004). There were no differences in CBGM between both groups at 60 and 120 min. We found differences between the groups in MAGE at 120 min (NORMAL 82.86 mg/dL [4.6 mmol/L] versus DUAL 54.76 mg/dL [3.04 mmol/L]; P = .0008). We observed no differences in the number of hypoglycemic episodes in both groups. CONCLUSION: Applying an additional dose of insulin in dual wave bolus for high-protein mixed meal improved PPG. We observed no statistically significant increase in the number of hypoglycemic episodes associated with this intervention.

High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study.

AIM: Despite its characteristic symptoms, type 1 diabetes (T1D) is still diagnosed late causing the development of diabetic ketoacidosis (DKA). The aim of this study was to estimate the incidence of DKA and factors associated with the development of acidosis at T1D recognition in Polish children aged 0-17. METHODS: The study population consisted of 2100 children with newly diagnosed T1D in the years 2010-2014 in 7 hospitals in eastern and central Poland. The population living in these areas accounts for 35% of the Polish population. DKA was defined as a capillary pH < 7.3, blood glucose > 11 mmol/L. The analyzed data included age, sex, diabetes recognition, pH, glycated hemoglobin (HbA1c), fasting C-peptide, and body mass index standard deviation score (BMI-SDS). RESULTS: We observed DKA in 28.6% of children. There were 2 peaks in DKA occurrence: in children <5 years of age (33.9%) and aged 10-12 (34%). The highest incidence of DKA was noted in children aged 0-2 (48.4%). In the group with DKA, moderate and severe DKA occurred in 46.7% of children. Girls and children <2 years of age were more prone to severe DKA. The multiple logistic regression analysis showed the following factors associated with DKA: age (P = .002), fasting C-peptide (P = .0001), HbA1c (P = .0001), no family history of T1D (P = .0001), and BMI-SDS (P = .0001). CONCLUSIONS: The incidence of DKA is high and remained unchanged over the last 5 years. Increasing the awareness of symptoms of DKA is recommended among children <5 years of age (especially <2 years of age) and aged 10-12. Children <2 years of age and girls were at the highest risk of severe DKA.

Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry.

BACKGROUND: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. OBJECTIVE: To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. METHODS: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out. RESULTS: Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001). CONCLUSIONS: Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

Bolus calculator and wirelessly communicated blood glucose measurement effectively reduce hypoglycaemia in type 1 diabetic children - randomized controlled trial.

BACKGROUND: The aim of this study was to assess the effect of bolus calculator function and wireless communication between insulin pump and blood glucose metre on metabolic control in children with type 1 diabetes, treated with insulin pumps. METHODS: In this randomized, controlled, 12-week trial, 156 patients, aged 12.9 ± 2.6 years, with a history of diabetes of 5.1 ± 3.3 years and glycated haemoglobin values of 7.3 ± 1.2% (56.3 ± 13.44 mmol/mol) were included. Children were assigned to one of three arms: group A, subjects using bolus calculator and wireless communication between insulin pump and blood glucose metre; group B, subjects using bolus calculator without communication between the devices and group C, control group. Devices were downloaded at 0, 6 and 12 weeks. RESULTS: There were statistically fewer episodes of hypoglycaemia in children using bolus calculator compared with the control group: A versus C (3.8 ± 3.1 versus 7.8 ± 5.13 episodes/2 weeks, respectively, p < 0.0001); B versus C (3.6 ± 3.3 versus 7.8 ± 5.1 episodes/2 weeks, respectively, p < 0.0001). Patients in group A used bolus calculator function significantly more frequently than patients in group B (4.9 ± 3.4 versus 2.5 ± 2.9 times/24 h, respectively, p = 0.0006). No significant differences in glycated haemoglobin levels were found between the experimental and the control groups: group A versus C (p = 0.699). The use of bolus calculator did not influence post-prandial glycaemia, body mass index-SD score or insulin/kg/24 h. CONCLUSIONS: Bolus calculator use reduces hypoglycaemic episodes independently of communication between insulin pump and blood glucose metre. Wireless communication between devices results in more frequent bolus calculator use.

High prevalence of depressive symptoms in well-controlled adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion.

BACKGROUND: Researchers report co-morbid depressive symptoms in children with poorly controlled type 1 diabetes (T1D). However, excellent diabetes control may be associated with emotional distress as well. The aim of this study was to evaluate the prevalence of depressive symptoms in T1D children with HbA1c <7.5% and ≥ 7.5% treated with insulin pump. METHODS: A total of 372 children (186 girls) with a mean age of 14.2 ± 2.0 years and mean diabetes duration of 5.3 ± 3.5 years were included. All subjects were treated for T1D for a minimum of 1 year. Children filled out a Polish version of the Children's Depression Inventory (CDI) and answered questions in the Quality of Life Questionnaire. Statistical analysis was made using Student's t-test, Mann-Whitney U-test, Fisher's exact test and Spearman's rank correlation. RESULTS: Eighteen per cent (31/177) of participants with HbA1c <7.5% and 21% (41/195) with HbA1c ≥ 7.5% reported depressive symptoms (CDI scores ≥ 13). Adolescents with HbA1c <7.5% and CDI ≥ 13 had higher total insulin dose (p = 0.039) and longer diabetes duration (p = 0.043) than subjects with CDI < 13. There was no difference in prevalence of depressive symptoms among patients with HbA1c ≥ 7.5% and HbA1c <7.5% (odds ratio [1.25 95% confidence interval (CI) 0.75-2.11], p = 0.432). In both groups, adolescents with CDI ≥ 13 had worse quality of life than those with CDI < 13 (p < 0.0001). CONCLUSIONS: In both groups, one in five adolescents with either good or poor glycemic control had depressive symptoms compared with <7% in subjects without diabetes. Long-lasting T1D significantly increased the risk of depressive symptoms in well-controlled youth. Depressive symptoms strongly affected the quality of life regardless of diabetes control.

Disease associated clinical factors and FTO polymorphism: effect on body mass in children with type 1 diabetes mellitus.

BACKGROUND: One of the consequences of excessive weight gain during insulin therapy in type 1 diabetes mellitus (T1DM) is an increased predisposition to cardiovascular diseases (CVD). Not only clinical but also genetic factors may play a role in the pathogenesis of this phenomenon. The aim of this study was to evaluate the prevalence of cardiovascular disease risk factors as well as the fat mass and obesity associated (FTO) gene rs9939609 variant in a large group of children with T1DM of the same ethnic-Polish origin. A total of 1237 children with T1DM and 1015 controls were recruited. RESULTS: The proportions of patients with obesity, hypertension, and abnormal LDL-cholesterol levels among children with T1DM were significantly higher than those in the non-diabetic. There was a higher rate of overweight, central obesity, and abnormal LDL-cholesterol levels among girls in comparison to that in boys in the group of children with diabetes. Children with inadequate metabolic control were characterized by the presence of more CVD risk factors. Similar differences were observed in children treated with the use of pens versus those using insulin pumps. The FTO gene single nucleotide polymorphism (SNP) correlated with body mass index (BMI) in both control and diabetic children, but the effect was lesser in diabetics. In a regression model the current BMI-SDS value in diabetics was significantly affected by the baseline BMI, disease duration, metabolic control, and subject's sex, but not the FTO genotype. CONCLUSIONS: Clinical rather than genetic factors have a greater impact on the development of overweight and obesity in insulin-treated children

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.