TY - JOUR
T1 - Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk
AU - The TRIGR Investigators
AU - Nucci, Anita M.
AU - Virtanen, Suvi M.
AU - Cuthbertson, David
AU - Ludvigsson, Johnny
AU - Einberg, Ulle
AU - Huot, Celine
AU - Castano, Luis
AU - Aschemeier, Bärbel
AU - Becker, Dorothy J.
AU - Knip, Mikael
AU - Krischer, Jeffrey P.
AU - Mandrup-Poulsen, Thomas
AU - Arjas, Elias
AU - Läärä, Esa
AU - Lernmark, Åke
AU - Schmidt, Barbara
AU - Åkerblom, Hans K.
AU - Hyytinen, Mila
AU - Knip, Mikael
AU - Koski, Katriina
AU - Koski, Matti
AU - Pajakkala, Eeva
AU - Salonen, Marja
AU - Shanker, Linda
AU - Bradley, Brenda
AU - Dosch, Hans Michael
AU - Dupré, John
AU - Fraser, William
AU - Lawson, Margaret
AU - Mahon, Jeffrey L.
AU - Sermer, Mathew
AU - Taback, Shayne P.
AU - Becker, Dorothy
AU - Franciscus, Margaret
AU - Nucci, Anita
AU - Palmer, Jerry
AU - Catteau, Jacki
AU - Howard, Neville
AU - Crock, Patricia
AU - Craig, Maria
AU - Clarson, Cheril L.
AU - Bere, Lynda
AU - Thompson, David
AU - Metzger, Daniel
AU - Marshall, Colleen
AU - Kwan, Jennifer
AU - Stephure, David K.
AU - Pacaud, Daniele
AU - Schwarz, Wendy
AU - White, Neil
N1 - Funding Information:
This work was supported by grant numbers HD040364, HD042444 and HD051997 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Special Statutory Funding Program for Type 1 Diabetes Research administered by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), the Canadian Institutes of Health Research, JDRF International, the Academy of Finland, the Commission of the European Communities (specific RTD programme ‘Quality of Life and Management of Living Resources’, contract number QLK1-2002-00372 ‘Diabetes Prevention’; this work does not reflect the Commission’s views and in no way anticipates the Commission’s future policy in this area) and the EFSD/JDRF/Novo Nordisk Focused Research Grant. The study formulas were provided free of charge by Mead Johnson Nutrition.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
PY - 2021/4
Y1 - 2021/4
N2 - 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 Graphical abstract: [Figure not available: see fulltext.]
AB - 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 Graphical abstract: [Figure not available: see fulltext.]
KW - Beta cell autoimmunity
KW - Childhood growth
KW - Genetic risk
KW - Length
KW - Type 1 diabetes
KW - Weight
UR - http://www.scopus.com/inward/record.url?scp=85099655644&partnerID=8YFLogxK
U2 - 10.1007/s00125-020-05358-3
DO - 10.1007/s00125-020-05358-3
M3 - Article
C2 - 33474583
AN - SCOPUS:85099655644
SN - 0012-186X
VL - 64
SP - 826
EP - 835
JO - Diabetologia
JF - Diabetologia
IS - 4
ER -