Growth and development of islet autoimmunity and type 1 diabetes in children genetically at riskShow others and affiliations
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
2021-02-202021-02-202022-03-17