期刊
DIABETOLOGIA
卷 64, 期 4, 页码 826-835出版社
SPRINGER
DOI: 10.1007/s00125-020-05358-3
关键词
Beta cell autoimmunity; Childhood growth; Genetic risk; Length; Type 1 diabetes; Weight
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [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') [QLK1-2002-00372]
- Canadian Institutes of Health Research
- JDRF International
- Academy of Finland
In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with an increased risk of progression from multiple IA to type 1 diabetes and with the development of type 1 diabetes, but not with the development of IA. Future studies should assess the impact of weight management strategies on these outcomes.
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
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