Anita M Nucci1, Suvi M Virtanen2,3,4,5, David Cuthbertson6, Johnny Ludvigsson7, Ulle Einberg8, Celine Huot9, Luis Castano10, Bärbel Aschemeier11, Dorothy J Becker12, Mikael Knip13,14,15,16, Jeffrey P Krischer6. 1. Department of Nutrition, Georgia State University, Atlanta, GA, USA. anucci@gsu.edu. 2. Welfare and Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland. 3. Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland. 4. Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland. 5. The Science Center of Pirkanmaa Hospital District, Tampere, Finland. 6. Pediatrics Epidemiology Center, University of South Florida, Tampa, FL, USA. 7. Crown Princess Victoria Children's Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. 8. Tallinn Children's Hospital, Tallinn, Estonia. 9. CHU Ste. Justine, Montreal, QC, Canada. 10. Cruces, University Hospital, Biocruces Bizkaia Research Institute, UPV/EHU, CIBERDEM, CIBERER, Endo-ERN, Bilbao, Bizkaia, Spain. 11. Diabetes Centre for Children and Adolescents, Children's and Adolescent's Hospital AUF DER BULT, Hannover, Germany. 12. Division of Endocrinology, University of Pittsburgh and UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. 13. Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 14. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 15. Folkhälsan Research Center, Helsinki, Finland. 16. Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Abstract
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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777.
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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777.
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