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Background: Children presenting to primary care with suspected type 1 diabetes should be referred immediately to secondary care to avoid life-threatening diabetic ketoacidosis. However, early recognition of children with type 1 diabetes is challenging. Children might not present with classic symptoms, or symptoms might be attributed to more common conditions. A quarter of children present with diabetic ketoacidosis, a proportion unchanged over 25 years. Our aim was to investigate whether a machine-learning algorithm could lead to earlier detection of type 1 diabetes in primary care., Methods: We developed the predictive algorithm using Welsh primary care electronic health records (EHRs) linked to the Brecon Dataset, a register of children newly diagnosed with type 1 diabetes. Children were included from their first primary care record within the study period of Jan 1, 2000, to Dec 31, 2016, until either type 1 diabetes diagnosis, they turned 15 years of age, or study end. We developed an ensemble learner (SuperLearner) using 26 potential predictors. Validation of the algorithm was done in English EHRs from the Clinical Practice Research Datalink (primary care) and Hospital Episode Statistics, focusing on the ability of the algorithm to identify children who went on to develop type 1 diabetes and the time by which diagnosis could be anticipated., Findings: The development dataset comprised 34 754 400 primary care contacts, relating to 952 402 children, and the validation dataset comprised 43 089 103 primary care contacts, relating to 1 493 328 children. Of these, 1829 (0·19%) children younger than 15 years in the development dataset, and 1516 (0·10%) in the validation dataset had a reliable date of type 1 diabetes diagnosis. If set to give an alert in 10% of contacts, an estimated 71·6% (95% CI 68·8-74·4) of the children with type 1 diabetes would receive an alert by the algorithm in the 90 days before diagnosis, with diagnosis anticipated, on average, by an estimated 9·34 days (95% CI 7·77-10·9)., Interpretation: If implemented into primary care settings, this predictive algorithm could substantially reduce the proportion of patients with new-onset type 1 diabetes presenting in diabetic ketoacidosis. Acceptability of alert thresholds should be explored in primary care., Funding: Diabetes UK., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Type 1 diabetes (T1D) is a chronic autoimmune disease of childhood affecting 1:500 children aged under 15 years, with around 25% presenting with life-threatening diabetic ketoacidosis (DKA). While first-degree relatives have the highest risk of T1D, more than 85% of children who develop T1D do not have a family history. Despite public health awareness campaigns, DKA rates have not fallen over the last decade. T1D has a long prodrome, and it is now possible to identify children who go on to develop T1D with a high degree of certainty. The reasons for identifying children presymptomatically include prevention of DKA and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. Research studies of population-based screening strategies include using islet autoantibodies alone or in combination with genetic risk factors, both of which can be measured from a capillary sample. If found during screening, the presence of two or more islet autoantibodies has a high positive predictive value for future T1D in childhood (under 18 years), offering an opportunity for DKA prevention. However, a single time-point test will not identify all children who go on to develop T1D, and so combining with genetic risk factors for T1D may be an alternative approach. Here we discuss the pros and cons of T1D screening in the UK, the different strategies available, the knowledge gaps and why a T1D screening strategy is needed., Competing Interests: Competing interests: REJB reports receiving speaking honoraria from Springer Healthcare and Eli Lilly, and reports sitting on the NovoNordisk UK Foundation Research Selection Committee on a voluntary basis. TR reports receiving consultancy fees from Abbott Diabetes Care (specifically for Libre evidence reviews) and lecture/programme organiser fees from Novo Nordisk. CMD reports having been an advisor giving honorarium lectures to NovoNordisk, Sanofi-genzyme, Janssen, Servier, Lilly, AstraZeneca, Provention Bio, UCB, MSD and Vielo Bio. CMD holds a joint patent with Midatech. JWG chairs the NovoNordisk UK Foundation Research Selection Committee and is a Foundation Trustee. TB reports receiving speaking honoraria from AstraZeneca, Servier and Novo Nordisk, and has received consultancy fees from Novo Nordisk and is an NN Global Expert Panel., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the delivery of home and hospital management at diagnosis of type 1 diabetes in childhood and any impact this had on health professionals delivering care., Methods: This qualitative study was undertaken as part of the Delivering Early Care in Diabetes Evaluation randomized controlled trial where participants were individually randomized to receive initiation of management at diagnosis, to home or hospital. Semi-structured telephone interviews were planned with a purposive sample of health professionals involved with the delivery of home and hospital management, to include consultants, diabetes and research nurses, and dieticians from the eight UK centres taking part. The interview schedule focused on their experiences of delivering the two models of care; preferences, impact, and future plans. Data were subject to thematic analysis., Results: Twenty-two health professionals participated, represented by consultants, diabetes and research nurses, and dieticians. Overall, nurses preferred home management and perceived it to be beneficial in terms of facilitating a unique opportunity to understand family life and provide education to extended family members. Nurses described a special bond and lasting relationship that they developed with the home managed children and families. Consultants expressed concern that it jeopardized their relationship with families. Dieticians reported being unable to deliver short bursts of education to families in the home managed arm. All health professionals were equally divided over which was logistically easier to deliver., Conclusions: A hybrid approach, of a brief stay in hospital and early home management, offers a pragmatic solution to the advantages and challenges presented by both systems., (© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Aims/hypothesis: The aim of this study was to describe the characteristics and outcomes of pregnancies in a national cohort of teenage (<20 years) and young adult women (≥20 years) with and without childhood-onset (<15 years) type 1 diabetes. We hypothesised that, owing to poor glycaemic control during the teenage years, pregnancy outcomes would be poorer in teenage mothers with type 1 diabetes than young adult mothers with type 1 diabetes and mothers without diabetes., Methods: The Brecon Register of childhood-onset type 1 diabetes diagnosed in Wales since 1995 was linked to population-based datasets in the Secure Anonymised Information Linkage (SAIL) Databank, creating an electronic cohort (e-cohort) of legal births (live or stillbirths beyond 24 weeks' gestation) to women aged less than 35 years between 1995 and 2013 in Wales. Teenage pregnancy rates were calculated based on the number of females in the same birth cohort in Wales. Pregnancy outcomes, including pre-eclampsia, preterm birth, low birthweight, macrosomia, congenital malformations, stillbirths and hospital admissions during the first year of life, were obtained from electronic records for the whole Welsh population. We used logistic and negative binomial regression to compare outcomes among teenage and young adult mothers with and without type 1 diabetes., Results: A total of 197,796 births were eligible for inclusion, including 330 to girls and women with childhood-onset type 1 diabetes, of whom 68 were teenagers (age 14-19 years, mean 17.9 years) and 262 were young adults (age 20-32 years, mean 24.0 years). The mean duration of diabetes was 14.3 years (9.7 years for teenagers; 15.5 years for young adults). Pregnancy rates were lower in teenagers with type 1 diabetes than in teenagers without diabetes (mean annual teenage pregnancy rate between 1999 and 2013: 8.6 vs 18.0 per 1000 teenage girls, respectively; p < 0.001). In the background population, teenage pregnancy was associated with deprivation (p < 0.001), but this was not the case for individuals with type 1 diabetes (p = 0.85). Glycaemic control was poor in teenage and young adult mothers with type 1 diabetes (mean HbA 1c based on closest value to conception: 81.3 and 80.2 mmol/mol [9.6% and 9.5%], respectively, p = 0.78). Glycaemic control improved during pregnancy in both groups but to a greater degree in young adults, who had significantly better glycaemic control than teenagers by the third trimester (mean HbA 1c : 54.0 vs 67.4 mmol/mol [7.1% vs 8.3%], p = 0.01). All adverse outcomes were more common among mothers with type 1 diabetes than mothers without diabetes. Among those with type 1 diabetes, hospital admissions during the first year of life were more common among babies of teenage vs young adult mothers (adjusted OR 5.91 [95% CI 2.63, 13.25]). Other outcomes were no worse among teenage mothers with type 1 diabetes than among young adult mothers with diabetes., Conclusions/interpretation: Teenage girls with childhood-onset type 1 diabetes in Wales are less likely to have children than teenage girls without diabetes. Teenage pregnancy in girls with type 1 diabetes, unlike in the background population, is not associated with social deprivation. In our cohort, glycaemic control was poor in both teenage and young adult mothers with type 1 diabetes. Pregnancy outcomes were comparable between teenage and young adult mothers with type 1 diabetes, but hospital admissions during the first year of life were five times more common among babies of teenage mothers with type 1 diabetes than those of young adult mothers with diabetes.

Context & Objectives: The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior., Design & Participants: Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported., Results: There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children., Conclusions: There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine whether, in children with newly diagnosed type 1 diabetes who were not acutely unwell, management at home for initiation of insulin treatment and education of the child and family, would result in improved clinical and psychological outcomes at 2 years postdiagnosis., Design: A multicentre randomised controlled trial (January 2008/October 2013)., Setting: Eight paediatric diabetes centres in England, Wales and Northern Ireland., Participants: 203 clinically well children aged under 17 years, with newly diagnosed type 1 diabetes and their carers., Intervention: Management of the initiation period from diagnosis at home, for a minimum of 3 days, to include at least six supervised injections and delivery of pragmatic educational care., Main Outcome Measures: Primary outcome was glycosylated haemoglobin (HbA1c) concentration at 24 months postdiagnosis. Secondary outcomes included coping, anxiety, quality of life and use of NHS resources., Results: 203 children, newly diagnosed, were randomised to commence management at home (n=101) or in hospital (n=102). At the 24 month primary end point, there was one withdrawal and a follow-up rate of 194/202 (96%). Mean HbA1c in the home treatment arm was 72.1 mmol/mol and in the hospital treated arm 72.6 mmol/mol. There was a negligible difference between the mean HbA1c levels in the two arms adjusted for baseline (1.01, 95% CI 0.93 to 1.09). There were mostly no differences in secondary outcomes at 24 months, apart from better child self-esteem in the home-arm. No home-arm children were admitted to hospital during initiation and there were no adverse events at that time. The number of investigations was higher in hospital patients during the follow-up period. There were no differences in insulin regimens between the two arms., Conclusions: There is no evidence of a difference between home-based and hospital-based initiation of care in children newly diagnosed with type 1 diabetes across relevant outcomes., Trial Registration Number: ISRCTN78114042., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate primary care presentations during the prodrome (12 months prior to onset type-1 diabetes (T1D), with or without diabetic ketoacidosis [DKA]), to identify opportunities for earlier diagnosis., Methods: This was a case-control study, linking 16 years of data from children (≤15 years) registered at diagnosis of T1D, and routinely collected primary care records in Wales (United Kingdom). Controls (without T1D) were matched on a 3:1 ratio. Conditional logistic regression modeling was used to compare characteristics occurring in cases (children with T1D) and controls; and cases that presented with/without DKA., Results: A total of 1345 children with T1D (19% DKA) and 4035 controls were identified. During the 12 months prior to diagnosis, cases were 6.5 times more likely to have at least one primary care contact (P < 0.001). One to 30 days prior to diagnosis, contacts relating to blood tests, fungal conditions, respiratory tract infections (RTIs), urinary conditions, vomiting, and weight were independently associated with T1D, as were contacts relating to blood tests, between 91 and 180 days prior to diagnosis. Children with a contact up to a month prior to diagnosis, relating to RTIs, antibiotic prescriptions, and vomiting, were more likely to present in DKA, as were boys (P = 0.047)., Conclusion: There are opportunities in primary care for an earlier diagnosis of T1D in childhood. These data could be used to create a predictive diagnostic tool, as a potential aid for primary care health professionals, to prevent presentation in DKA., (© 2019 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Type 1 diabetes mellitus (T1DM) is a common chronic disease in children and young people. Living with diabetes can pose many challenges both medical and psychological. Disordered eating behaviours, intentional insulin omission and recognised eating disorders are common among young people with diabetes and are associated with increased risk of short-term and long-term complications and death. Recognition of these behaviours is important to ensure that relevant support is provided. Joint working between diabetes and mental health teams has challenges but is essential to ensure all needs are met during treatment and recovery., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There is increased incidence of new cases of type 1 diabetes in children younger than 15 years. The debate concerning where best to manage newly diagnosed children continues. Some units routinely admit children to hospital whilst others routinely manage children at home. A Cochrane review identified the need for a large well-designed randomised controlled trial to investigate any significant differences in comprehensive short and long-term outcomes between the two approaches. The DECIDE study will address these knowledge gaps, providing high quality evidence to inform national and international policy and practice., Methods/design: This is a multi-centre randomised controlled trial across eight UK paediatric diabetes centres. The study aims to recruit 240 children newly diagnosed with type 1 diabetes and their parents/carers. Eligible patients (aged 0-17 years) will be remotely randomised to either 'hospital' or 'home' management. Parents/carers of patients will also be recruited. Nursing management of participants and data collection will be co-ordinated by a project nurse at each centre. Data will be collected for 24 months after diagnosis; at follow up appointments at 3, 12 and 24 months and every 3-4 months at routine clinic visits.The primary outcome measure is patients' glycosylated haemoglobin (HbA1c) at 24 months after diagnosis. Additional measurements of HbA1c will be made at diagnosis and 3 and 12 months later. HbA1c concentrations will be analysed at a central laboratory.Secondary outcome measures include length of stay at diagnosis, growth, adverse events, quality of life, anxiety, coping with diabetes, diabetes knowledge, home/clinic visits, self-care activity, satisfaction and time off school/work. Questionnaires will be sent to participants at 1, 12 and 24 months and will include a questionnaire, developed and validated to measure impact of the diagnosis on social activity and independence. Additional qualitative outcome measures include the experience of both approaches by a subgroup of participants (n = 30) and health professionals. Total health service costs will be evaluated. A cost effectiveness analysis will assess direct and indirect health service costs against the primary outcome (HbA1c)., Discussion: This will be the first randomised controlled trial to evaluate hospital and home management of children newly diagnosed with type 1 diabetes and the findings should provide important evidence to inform practice and national guidelines., Trial Registration Number: ISRCTN: ISRCTN78114042.