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      The incidence of type 1 diabetes in children under 15 years of age is rising again—a nationwide study

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          Abstract

          International incidence rates (IRs) and trends of childhood type 1 diabetes (T1D) vary. Recent data from Ireland and other high incidence countries suggested a stabilisation in IRs of T1D in children aged under 15 years. Our primary objective was to report the IR of T1D in children in Ireland from 2019 to 2021 and evaluate if age, sex and season of diagnosis had changed. Incident cases of T1D in those aged under 15 years were identified prospectively by clinicians nationally and reported to the Irish Childhood Diabetes National Register (ICDNR). Following case verification, capture-recapture methodology was applied, and IRs calculated. Numbers of children including age, sex and season of diagnosis per year were evaluated. There were 1027 cases, 542 males (53%). The direct standardised incidence rates (SIRs) increased by 21% overall and were 31.1, 32.2 and 37.6/100,000/year, respectively, with no significant sex difference. The highest IRs were in the 10–14-year category until 2021, then changed to the 5–9-year category (40% of cases). Whilst autumn and winter remain dominant diagnostic seasons, seasonality differed in 2021 with a greater number presenting in spring.

          Conclusion: The incidence of childhood T1D in Ireland is increasing, observed prior to the COVID-19 pandemic, and shifting to an earlier age at diagnosis for the first time. The pattern of seasonality also appears to have changed. This may reflect an increased severity of diabetes with important implications for healthcare providers.

          What is Known:

          • Ireland has a very high incidence of T1D in childhood, which had stabilised following a rapid rise, similar to other high incidence countries.

          • The incidence rate is consistently highest in older children (10–14 years).

          What is New:

          • Irish IR is no longer stable and has increased again, with the highest incidence occurring in the younger 5-9 age category for the first time.

          • The seasonality of diagnosis has changed during the COVID-19 pandemic years of 2020–2021.

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          Most cited references21

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          Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989–2013: a multicentre prospective registration study

          Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years.
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            Environmental risk factors for type 1 diabetes.

            The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to β cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens.
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              Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes

              The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
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                Author and article information

                Contributors
                rocheef@tcd.ie
                Journal
                Eur J Pediatr
                Eur J Pediatr
                European Journal of Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-6199
                1432-1076
                8 August 2023
                8 August 2023
                2023
                : 182
                : 10
                : 4615-4623
                Affiliations
                [1 ]The Discipline of Paediatrics, School of Medicine, Trinity College Dublin, ( https://ror.org/02tyrky19) Dublin, Ireland
                [2 ]The Research and Evidence Office, Health Service Executive, ( https://ror.org/04zke5364) Dublin, Ireland
                [3 ]GRID grid.413305.0, ISNI 0000 0004 0617 5936, The Department of Paediatric Growth, Diabetes, and Endocrinology, , Children’s Health Ireland (CHI) at, Tallaght University Hospital, ; Dublin, Ireland
                Author notes

                Communicated by Gregorio Milani

                Author information
                http://orcid.org/0000-0001-7266-8649
                Article
                5125
                10.1007/s00431-023-05125-7
                10587220
                37550598
                2c6c0899-5901-42ad-8fc7-8cf10e191bed
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 March 2023
                : 8 June 2023
                : 18 July 2023
                Funding
                Funded by: National Children’s Hospital Foundation (NCHF). The ICDNR is supported equally by an unrestricted grant from Novo Nordisk Ltd and an unrestricted grant from Abbott Laboratories Ireland Ltd.
                Funded by: University of Dublin, Trinity College
                Categories
                Research
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Pediatrics
                type 1 diabetes,childhood,incidence rate,epidemiology
                Pediatrics
                type 1 diabetes, childhood, incidence rate, epidemiology

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