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Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk
Georgia State Univ, GA 30303 USA.
Finnish Inst Hlth & Welf, Finland; Tampere Univ, Finland; Tampere Univ, Finland; Tampere Univ Hosp, Finland; Pirkanmaa Hosp Dist, Finland.
Univ S Florida, FL 33620 USA.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.ORCID iD: 0000-0003-1695-5234
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2021 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 64, no 4, p. 826-835Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. Methods Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10-14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. Results In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2-10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. Conclusions/interpretation In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. Graphical abstract

Place, publisher, year, edition, pages
SPRINGER , 2021. Vol. 64, no 4, p. 826-835
Keywords [en]
Beta cell autoimmunity; Childhood growth; Genetic risk; Length; Type 1 diabetes; Weight
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-173475DOI: 10.1007/s00125-020-05358-3ISI: 000609036400001PubMedID: 33474583OAI: oai:DiVA.org:liu-173475DiVA, id: diva2:1530033
Note

Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 Diabetes Research by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health; Commission of the European Communities (specific RTD programme Quality of Life and Management of Living Resources)European Union (EU) [QLK1-2002-00372]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); JDRF InternationalJuvenile Diabetes Research Foundation; Academy of FinlandAcademy of Finland

Available from: 2021-02-20 Created: 2021-02-20 Last updated: 2022-03-17

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Ludvigsson, Johnny
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Division of Children's and Women's HealthFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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