Agnieszka Szypowska

Aims/hypothesis: In the PROTECT randomised trial, teplizumab demonstrated significantly greater beta cell function preservation vs placebo in the intent-to-treat (ITT) population. Analyses of the pre-specified per-protocol (PP) population and PP subgroups are presented to further evaluate the efficacy of teplizumab. Methods: Participants aged 8–17 years with stage 3 type 1 diabetes with a peak stimulated C-peptide level ≥0.2 nmol/l (ITT population: N =328) were randomised 2:1 to receive two 12-day courses of teplizumab or placebo intravenously. Participants with n =180; placebo, n =95). At week 78, the primary endpoint of the least squares (LS) mean difference in change of stimulated C-peptide concentration from baseline between teplizumab and placebo was 0.14 nmol/l (95% CI 0.10, 0.18; p −1 day ⁻¹ ; 95% CI –0.26, –0.08; p p <0.05) vs placebo. In subgroup analyses, treatment with teplizumab resulted in higher C-peptide levels compared with placebo, regardless of HLA-DR3/HLA-DR4 presence or baseline type 1 diabetes autoantibodies. Conclusions/interpretation: Teplizumab treatment per protocol led to greater beta cell function preservation, greater TIR and lower exogenous insulin use compared with placebo. Beta cell function preservation was maintained irrespective of HLA subtype or the presence of type 1 diabetes autoantibodies. Trial registration: ClinicalTrials.gov NCT03875729 Funding: The study was funded by Provention Bio, a Sanofi company

Aims: To evaluate whether faster insulin aspart (FIA) improves time in range (TIR) compared with standard insulin aspart (SIA) in children and adolescents with type 1 diabetes achieving glycaemia close to target treated with continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM). Methods: This prospective, open‐label, randomized, 1:1 crossover trial included participants aged 6–17 years with T1D duration of ≥1 year, CSII use ≥3 months, CGM use ≥1 month, and HbA1c 64 mmol/mol (P = 0.322). Similar patterns were observed for additional glycaemic metrics. Time in tight range was also similar between treatments: 46.3% for SIA versus 45.4% for FIA ( P = 0.674). Conclusions: In this randomised crossover study of children and adolescents with T1D achieving glycaemia close to target on CSII, switching from SIA to FIA does not improve TIR. The absence of improvement across CGM‐derived metrics suggests that FIA does not meaningfully enhance glycaemic outcomes in this clinical setting.

Background/Objectives: Optimal postprandial glycemic control is crucial to maintain time in range (TIR:3.9–10.0 mmol/L, 70–180 mg/dL) and time in tight range (TITR:3.9–7.8 mmol/L, 70–140 mg/dL), both important to reduce microvascular complications in type 1 diabetes mellitus (T1DM). However, insulin dosing based on carbohydrate counting fails to compensate for delayed hyperglycemia from protein and fat. This study evaluated two advanced insulin dosing algorithms designed to improve postprandial control in adolescents with T1DM. Methods: In this randomized, prospective, double-blind, crossover trial, 58 adolescents with T1DM (median age 15.5 years) were enrolled, all using continuous subcutaneous insulin infusion and a continuous glucose monitoring system in non-automated mode. For two consecutive days, participants consumed standardized mixed meals for breakfast (50 g of carbohydrates, 200 kcal from protein and fat) and received an extended bolus delivered for four hours, based on the Pankowska Equation (PE, i.e., Fat-Protein Units × Insulin-to-Carbohydrate Ratio (ICR)) and the Sieradzki Equation (SE, i.e., 30% × Carbohydrate Units × ICR). Postprandial glucose was monitored for five hours using a glucometer and Continuous Glucose Monitoring (CGM). The primary outcome was the capillary blood glucose level at predefined time points. The secondary outcomes were the frequency of hypoglycemia and glycemic variability parameters. Results: Both methods kept postprandial glucose within the recommended TIR. The SE method provided longer TITR (82.51% vs. 70.49%, p = 0.6281) and fewer hypoglycemic episodes at 180 and 300 min. Glucose levels at 60 min, were higher after PE (136 ± 35.2 mg/dL vs. 124 ± 32.2 mg/dL, p = 0.016). Conclusions: Both algorithms provided effective postprandial control after a mixed meal, but SE achieved a longer TITR and fewer late hypoglycemic events.

Early detection of type 1 diabetes, in its presymptomatic stage, offers significant clinical advantages, including treatment that can delay disease onset. Current screening focuses on identifying islet autoantibody positivity, with proposed optimal testing at ages 2, 6 and 10 years potentially achieving up to 80% sensitivity. However, challenges arise from participation rates and costs associated with multiple screenings. Genetic pre-screening has been suggested as a complementary strategy to target high-risk individuals prior to autoantibody testing, but its real-world benefits remain uncertain. Broad genetic selection strategies, based on family history, HLA typing or polygenic risk scores, can identify subsets of the population at elevated risk. However, these approaches face issues like low recall rates, socioeconomic biases and limited applicability across diverse ancestries. Additionally, the cost-effectiveness and infrastructure requirements of integrating genetic testing into routine healthcare remain significant hurdles. The combined use of genetic and autoantibody testing could improve predictive value, especially with innovations like point-of-care genetic testing. Yet, the ultimate success of any screening programme depends less on specific strategies and more on maximising public and healthcare-provider engagement, ensuring high participation, and addressing socioeconomic and demographic disparities. Digital-health infrastructure may play a crucial role in improving recall rates and maintaining follow-up adherence. In conclusion, while repeated islet autoantibody screening remains the most effective standalone approach, conducting genetic screening prior to islet autoantibody testing may be practical in certain contexts, provided that sufficient resources and equitable strategies are employed. Public engagement and robust infrastructure are essential to realising the full potential of early type 1 diabetes detection programmes. Graphical Abstract

Objective: Seasonal variation in type 1 diabetes (T1D) incidence has long been a focus of epidemiological research, with viral infections among the proposed contributing factors. Our aim was to examine the seasonal pattern of T1D onset in Poland and to assess how viral infections—including COVID‐19—may influence this seasonality. Methods: We analyzed data from 2381 children with newly diagnosed T1D admitted to two pediatric diabetes centers in the Masovian Voivodeship between 2015 and 2023 and compared them with epidemiological data on COVID‐19 and influenza cases during the same period. Results: Our analysis revealed a 30% increase in T1D cases over the study period, with a pronounced seasonal pattern: the highest number of diagnoses occurred in February and the lowest was noted in June. Children under 4 years of age exhibited a distinct pattern with a peak in October, suggesting age‐specific differences in T1D pathogenesis. Overall, T1D onset was more frequent in autumn–winter than in spring–summer, with 1294 (54%) vs. 1087 (46%) cases, respectively ( p < 0.0001). The influence of COVID‐19 on T1D incidence was limited to the first wave of the pandemic. During this period, a strong association was observed ( r = 0.96, p < 0.001), whereas no correlation was found during the second wave ( r = 0.086, p = 0.87). The seasonality of T1D diagnoses closely correlated with that of influenza infections ( r = 0.79, p = 0.002). However, the overall trends differed, suggesting that other viruses with similar transmission patterns may contribute to the seasonality of T1D onset. Conclusion: These findings underline the complex interplay between viral infections and T1D seasonality and suggest that public health strategies aimed at mitigating severe viral infections, including vaccination, warrant further investigation for their potential role in modulating T1D onset in susceptible individuals.

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.

Background: Time in range is a reliable measure of the risk of diabetes complications. High percentage of patients with diabetes fail to achieve the recommended time in range (TIR) target of 70–180 mg/dl (3.9–10 mmol/l) >70%. Objective: This study aimed to identify factors influencing TIR prolongation. Methods: Children aged 1–17 years with >1-year type 1 diabetes (T1D) duration, treated with continuous subcutaneous insulin infusion (CSII) ≥3 months, using continuous glucose monitoring (CGM) or intermittently scanned CGM (is-CGM) ≥1 month, and with a registration time >70% were included. Data were collected during routine diabetology visits at an outpatient clinic. Insulin pump and CGM or is-CGM reports in the most recent 14 days were recorded using a dedicated software. Legal caregivers were also asked to complete a questionnaire on how the patients use the insulin pump functions and eating habits. Results: A sample of 110 patients was categorized into two groups: those with TIR >70% and TIR ≤70%. TIR ≤70% group presented with repeated hyperglycemia and a high glycemic variability coefficient of variation. We noted an acceptable hypoglycemia rate (3%), regardless of the TIR value. Patients with TIR >70% predominantly used predictive low glucose suspend system, maintained adequate intervals between insulin delivery and meal consumption, used the “bolus calculator” function, and more frequently created electronic reports. Conclusions: Hyperglycemia and high glycemic variability prevent patients from achieving the target TIR. Advanced features in the CGM systems, premeal insulin bolus, and patients’ involvement in diabetes treatment are the main factors contributing to TIR prolongation.

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).

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.