Children with early-stage (pre-symptomatic) type 1 diabetes are currently identified primarily via research-based screening programmes in Australia. Once identified, families live with the knowledge that their child has an increased chance of developing symptomatic, lifelong, insulin-requiring type 1 diabetes but have no specific clinical pathway available to them in Western Australia (WA) for accessing tailored support or education. This project aimed to co-design a new clinical pathway to address this unmet need. Experience-based co-design (EBCD) methodology was applied, comprising three phases undertaken consecutively over 12 months. Recruitment for each phase was via open invitation with voluntary participation. Phases 1 and 2 involved facilitated community conversations and focus groups conducted separately for type 1 diabetes community members and healthcare professionals (HCPs). Data from these phases were analysed using deductive and inductive content analysis to identify key categories of information and a prototype clinical pathway was developed incorporating these. For phase 3, a combined workshop was held with all stakeholders to obtain feedback on the prototype, and refine it accordingly. In phase 1, 16 community members (people living with type 1 diabetes, families whose child or children had been screened for type 1 diabetes) and 36 HCPs (doctors, nurse educators, social workers, dietitians, a mental health nurse and administrative staff from Perth Children’s Hospital) participated in separate community conversations. The following three key categories were identified: (1) the need for education; (2) the need for support and strategies for managing uncertainty; and (3) the need for information on disease-modifying therapies and access to clinical trials. In phase 2, seven community members and 11 HCPs participated in separate focus groups. The following key priorities were identified: (1) the need for access to HCPs skilled in supporting patients to manage uncertainty; (2) the need for flexibility in delivery modes (telehealth/in-person); (3) the need for early referral to relevant clinical trials; and (4) the need for reliable and up-to-date resources. In phase 3, three community members and three HCPs attended a combined workshop to provide feedback on a prototype clinical pathway and their feedback was incorporated into a final version. Application of EBCD methodology enabled the development of a new clinical pathway tailored to the needs of WA families with a child living with early-stage type 1 diabetes.

Enteroviruses (EVs) have long been implicated in the development of islet autoimmunity (IA) and type 1 diabetes (T1D). However, given the ubiquity of EV infections in children, disease susceptibility is likely driven by host-specific immune responses rather than viral exposure alone. To investigate the host antibody response to EVs, we employed virome-wide serological profiling (VirScan), to compare the EV antigen landscapes in children with IA-positive cases versus IA-negative controls across two independent paediatric cohorts separated by 12 years, using samples collected at the singular timepoint of seroconversion. For the first time, we identified a reproducible and distinct EV-specific antibody signature in IA-positive cases, with a borderline significant enriched immunogenic hotspot localised within a highly conserved region in the 3D RNA-dependent RNA polymerase. Additionally, IA-positive males exhibited heightened antibody responses against the VP1 capsid protein. Our findings provide paradigm-shifting evidence that differential antiviral humoral responses, rather than the specific type of EV infections, play a central role in IA development, highlighting the need for an updated framework to study host-virus interactions in autoimmune pathogenesis.

OBJECTIVE:To compare diet and physical activity during pregnancy in women with and without type 1 diabetes and assess against national dietary guidelines. RESEARCH DESIGN AND METHODS:Diet and physical activity were measured prospectively in 1,124 pregnancies using validated questionnaires. RESULTS:Diets exceeded recommended intake for fat, saturated fat, discretionary foods, sodium, vitamin C, calcium, and zinc and were below recommendations for carbohydrate, fruit, dairy, vegetables, grain foods, and lean meats and alternatives. Differences in dietary intake between women with and without type 1 diabetes were modest. Total, moderate, and vigorous physical activity decreased in the third trimester. Women with type 1 diabetes performed less vigorous intensity activity than women without type 1 diabetes. CONCLUSIONS:Most pregnant women with and without type 1 diabetes did not meet dietary guidelines. Physical activity patterns were also mostly similar in women with and without type 1 diabetes.

Background:Advances in the understanding of type 1 diabetes (T1D) natural history have enabled screening for islet autoantibodies and the detection of presymptomatic (early-stage) T1D prior to clinical presentation and the need for insulin replacement therapy. As screening programs expand, increasing numbers of children are being identified with early-stage T1D, creating a pressing need for relevant, accessible, evidence-based educational resources. Due to the rapidly changing paradigm of T1D care in such settings, many health care professionals currently lack awareness or guidance on which educational resources to recommend to families. To date, no review has systematically identified and evaluated educational resources for families navigating early-stage T1D or for health care professionals supporting them. Objective:This scoping review aims to (1) systematically identify and evaluate educational resources for early-stage T1D; (2) assess resource readability, understandability, quality, and credibility; (3) create an inventory of resources consistent with current care and health literacy guidelines; and (4) identify resource gaps and priorities for future development. Methods:A comprehensive search of peer-reviewed (MEDLINE, CINAHL, PsycInfo, and Scopus) and gray literature databases (Google advanced searches and targeted searches of professional organizations, advocacy groups, research consortiums, and screening programs) will be conducted to identify English-language resources (eg, fact sheets, websites, videos, and infographics). Resources must target, or be suitable for adaptation for, audiences including youth (aged <25 years), families, parents, carers, and/or health care professionals. Resources must provide information about early-stage T1D, monitoring of early-stage T1D, trajectories, psychosocial aspects, or care navigation. Eligible resources will undergo standardized assessment using validated tools for readability (Flesch-Kincaid Grade Level [FKGL] and Simple Measure of Gobbledygook [SMOG]), understandability (Patient Education Materials Assessment Tool [PEMAT]), information quality (Quality Evaluation Scoring Tool [QUEST]), and credibility (adherence to current early-stage T1D guidelines). Two reviewers will abstract data using a charting tool prepared for the study. Results:Resources will be grouped by type, audience, and origin. Readability, understandability, quality, and credibility assessments will be presented in tables. Resource gaps will be identified to make recommendations for future resource development. The review will begin in March 2026, and data extraction and analysis will be completed by August 2026, with manuscript submission by October 2026. Conclusions:This paper presents the protocol for the first scoping review to systematically compile and appraise educational resources for early-stage T1D. The findings will offer a clear overview of the current resource landscape, identify gaps, highlight resources that adhere to current early-stage T1D and health literacy guidelines, and provide a foundation for future development and co-design of fit-for-purpose materials.

Continuous glucose monitoring (CGM) of children with early-stage type 1 diabetes (T1D) identifies early glycemic anomalies associated with glycemic progression. This study applied machine learning on CGM features to identify glycemic patterns that precede stage 3 T1D. The aim of this study was to apply symbolic transformation and machine learning–based multilevel clustering approaches to cross-sectional CGM data from children with presymptomatic type 1 diabetes to identify glycemic patterns associated with progression to stage 3 T1D. Cross-sectional CGM data from 79 participants being longitudinally followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) study were analyzed using multilevel clustering frameworks applied at both daily and participant levels. Input features included time spent in glycemic ranges, area under the curve (AUC), average glycemic distribution, and glycemic variability metrics. Clustering of daily CGM profiles using k-means identified subgroups characterized by different proportions of CGM time in tight range, hyperglycemia and/or hypoglycemia. In parallel, participant level clustering was performed to identify subgroups of individual glycemic profiles consisting of multiple consecutive days. Six of the seven participants who progressed to stage 3 T1D within the study period were identified by one or more clustering approaches. Mathematical models and machine learning approaches to time-series data may provide novel insights from CGM data. A combination of symbolic transformation with statistical clustering at multiple temporal resolutions provides a robust framework for characterizing glycemic variability in CGM data. This exploratory approach could be applied to larger datasets to support early risk stratification and inform the development of CGM-based clinical surveillance strategies.

Objective: Reduced microbial short-chain fatty-acids (SCFA) have been implicated in type-1-diabetes (T1D) risk. We investigated fecal SCFA concentrations in mother-infant dyads from pregnancy to the onset of islet autoimmunity (IA) to test whether decreased fecal SCFA concentrations increase islet autoimmunity (IA) risk. Research design and methods Children with a first-degree relative with T1D and their mothers were followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort study. A nested case-control design included n=54 infant-cases that developed  1 persistent islet autoantibodies/clinical T1D and n=161 age- and sex-matched controls without IA. Stool (n=1120 samples) from each pregnancy trimester in mothers (median n=2 samples) and from birth in infants (median n=6 samples) up until IA onset were used to quantify SCFAs by LC/MS. Weighted-conditional logistic-regression and linear mixed-effect models investigated associations between SCFAs and IA-onset. Results Fecal SCFAs were not associated with IA-onset, and SCFA profiles through pregnancy and early-childhood were similar between cases and controls. Infant fecal SCFA concentrations increased until age 1 year. Introduction of solid foods significantly increased acetate (FDR=0.000028) and summed primary SCFA (FDR=0.00784) concentrations. Higher infant BMI z-scores correlated with higher fecal acetate (FDR=0.0767) and butyrate (FDR=0.0590). Mothers with T1D had lower acetate (FDR=0.0696), butyrate (FDR=0.0959) and propionate (FDR=0.0696) than mothers without T1D during pregnancy. Concentrations of these three SCFA were lower in infants of mothers with versus without T1D (FDR=0.0073, FDR=0.0603, 0.0479, respectively). Conclusion These data do not support that lower fecal SCFA concentrations across pregnancy and early-life are directly associated with IA development.

AIM:To explore the lived experiences of parents of children at risk of type 1 diabetes (T1D) undergoing repeated blinded continuous glucose monitoring (CGM). METHOD:Since 2021, children with persistent islet autoimmunity in the Environmental Determinants of Islet Autoimmunity (ENDIA) study have been invited to participate in a sub-study involving blinded Dexcom G6 CGM. Parents with children undergoing repeated CGM participated in a semi-structured audio call interview. Open-ended questions captured their experiences of their child's repeated blinded CGM. Data were analysed using inductive thematic analysis. RESULTS:Nineteen parents (18 mothers, 1 father) of children with a mean (SD) age of 7.5 (1.3) years, who had undergone a mean 5.5 (3.2) CGM assessments, were interviewed for a mean duration of 21.3 (8.0) minutes. Three main themes were identified: Challenges of CGM wear: All parents identified at least one difficult experience (e.g. pain with sensor insertion, anxiety of data loss) during CGM assessments Content and timing of feedback of CGM assessment findings: Parents described a range of experiences related to receiving feedback from health care professionals and their child's stage of T1D. Preparation for diagnosis of clinical (Stage 3) T1D and initiation of insulin treatment: Parents described feeling empowered by knowing their child's risk, allowing them to feel more prepared for progression to Stage 3 T1D. CONCLUSION:Despite the challenges parents face while their child undergoes CGM assessments, they reported repeated blinded CGM as an acceptable form of monitoring that provided valuable knowledge regarding their child's risk of stage 3 type 1 diabetes.

This cohort study examines whether there is a temporal association between SARS-CoV-2 infection and the development of islet autoimmunity among Australian children with a first-degree relative with type 1 diabetes.

Objectives: To characterise small-area geographical variation in the prevalence of diabetes in Australian youth. Methods: A combined statistical reconstruction and small-area estimation algorithm was applied to privacy-modulated data from the 2021 Australian Census. The census instrument and reconstruction accuracy was examined by comparisons against a hospital-based register and community register. Diabetes prevalence maps were created from the small-area estimates. Results: The median and interquartile range of estimated diabetes prevalence by small-area unit under our geospatial smoothing model were 1.76 [1.49–1.97] cases per 1000 population for those aged 0–14 years and 5.2 [4.4–5.9] cases per 1000 population for those aged 15–19 years old. Concentrations of elevated prevalence were identified in the vicinities of regional towns across South-East Queensland, regional New South Wales and regional Victoria. Across each of Australia’s five largest cities a gradient of decreasing youth diabetes prevalence from the outer suburbs to the urban centre was identified. Conclusion: Diabetes burden is systematically higher among rural and peri-urban resident youth in Australia compared with their urban counterparts. Implications for Public Health: Hotspots of prevalence in regional areas deserve attention from public health authorities.

OBJECTIVE:To characterize longitudinal continuous glucose monitoring (CGM) data in young children with presymptomatic type 1 diabetes. RESEARCH DESIGN AND METHODS:Between 2021 and 2024, children in the Australian ENDIA study with persistent multiple islet autoimmunity underwent blinded CGM assessments every 3-6 months. CGM-derived metrics (SD sensor glucose, coefficient of variation, mean sensor glucose, and percent CGM time >7.8 mmol/L [140 mg/dL]) were determined for each child by time from islet autoantibody detection. RESULTS:A total of 178 CGM assessments were analyzed for 36 children (median [Q1, Q3] age at first assessment 4.5 [3.5, 6.0] years) who underwent a median of 5.5 (2.0, 7.0) assessments of 11 (9, 15) days duration each. High within-person variability was observed in serial CGM metrics, including percent CGM time >7.8 mmol/L (140 mg/dL) (intraclass correlation coefficient 0.30). CONCLUSIONS:Further research is needed to inform interpretation of CGM-derived metrics in young children with presymptomatic type 1 diabetes.

AIMS:Evidence on outcomes of treating type 1 diabetes (T1D) with long-acting basal insulins in low-resourced settings is lacking. This study aimed to evaluate the impact of switching children and youth with T1D in the low-income country of Mali from human insulin via syringe to long-acting biosimilar insulin glargine delivered by reusable pens combined with short-acting insulin via syringe. METHODS:A two-group parallel design randomised trial was conducted enrolling 260 youth aged <25 years, diagnosed with T1D for ≥12 months without prior use of analogue insulin. Youth were randomised 1:1 to either continue receiving current therapy or switch to analogue insulin. The primary outcome was HbA1c, collected at baseline and 3-monthly for 12 months. RESULTS:Primary outcome data were available for 130 (100%) youth in the intervention group and 128 (98.5%) in the control group. Over the 12-month study period, mean HbA1c decreased from 103 to 65 mmol/mol (11.6%-8.1%) (p < 0.001) in the intervention group and from 101 to 93 mmol/mol (11.4% to 10.7%) in the control group (p < 0.01), an absolute difference of 30 mmol/mol (95% CI: -37, -24) (p < 0.001). The proportion of participants with HbA1c ≥130 mmol/mol (≥14%) decreased from 38.5% to 0% in the intervention group, versus 40.6% to 21.9% in the control group. CONCLUSIONS:Switching to a basal-bolus insulin regimen including biosimilar glargine resulted in marked improvements in HbA1c and diabetic ketoacidosis episodes. With relevant training, resources, and support, use of long-acting analogue insulin for treating T1D in Mali was feasible and acceptable to participants and healthcare professionals.

We aimed to assess perceived stress and influencing factors in mothers with children at risk of type 1 diabetes and coeliac disease who did, or did not, develop islet autoantibodies (IA) or coeliac autoantibodies (CA) by 4 years of age. Maternal perceived stress was assessed postpartum and when their child was approximately 4 years of age using the Perceived Stress Scale (range 1–56) in mothers followed prospectively in the multicentre Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy–birth cohort. Data were analysed using linear mixed models. In total, 818 mothers were included (642 children had no detected IA or CA [Ab negative], 97 had IA detected [IA positive] and 79 had CA detected [CA positive]). The development of IA or CA in young children did not add significantly to the perceived stress of their mothers at a median of 1.8 [IQR 0.8–2.5] and 1.6 [IQR 0.9–2.3] years later, respectively (Ab negative, adjusted predicted mean score 23.8 [95

AIMS:Globally, symptomatic type 1 diabetes (T1D) prevalence varies markedly. The International Diabetes Federation 11thEdition Atlas/T1D Index Version 3.0 estimated 2025 numbers for 202 countries/territories ("countries"), and projected to2040. METHODS:The T1D Index model, a Markov model with sub-models for incidence-over-time, adult incidence, and mortality-over-time, was updated with recent population-based T1D incidence, mortality and prevalence studies. For countries without studies, data were extrapolated from countries with similarsettings. RESULTS:There are estimated 9.5 million people living with T1D globally (compared to 8.4 million in 2021, a 13 % increase), with 1.0 million of these aged 0-14, and 0.8 million aged 15-19 years. In lower-income countries, prevalent cases increased by 20 % from 1.8 million in 2021 to 2.1 million in 2025. Incident cases in 2025 are an estimated 513,000 (164,000 aged 0-14 and 58,000 aged 15-19 years), with incidence increasing by 2.4 % in the last year. Premature deaths are estimated at 174,000, with 17.2 % of these due to non-diagnosis soon after clinical onset. The estimated remaining life expectancy of a 10-year-old child diagnosed with T1D in 2025 varies between countries from 6 to 66 years. There are still no data available for 119 countries. The projectedT1D population for 2040 is estimated to be14.7 million. CONCLUSIONS:The number of global T1D cases is rising quickly, especially in lower-income settings, due to increasing diagnosed incidence, falling mortality and ageing, and population growth. Contemporary data are unavailable for over 50% of all countries, highlighting need for epidemiological studies.

Islet autoantibodies herald early type 1 diabetes. However, less is known of the evolution of autoantibodies to the islet autoantigen ZnT8. Our primary aim was to characterise the development of islet autoantibodies in a pregnancy–birth at-risk cohort and to provide new knowledge about ZnT8A. Islet autoantibodies were measured every 3–6 months in 1277/1473 children with a first-degree relative with type 1 diabetes who were followed prospectively from pregnancy in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort for 7.0 (IQR 5.8–8.3) years. Islet autoantibodies were also measured in the mothers and/or in cord blood in 901 pregnancies with type 1 diabetes. The development of persistent IAA reached a probability of 0.02 by 2 years of age. A combination of IAA- and GADA-first, GADA-first and ZnT8A-first all reached a similar probability by 5 years of age. ZnT8A appeared as the first islet autoantibody, alone or in combination, in 43 (32

Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a ‘fresh food’ dietary pattern than women without type 1 diabetes (OR 1.19, 95