Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk.
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.
Overview publication
| Title | Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk. |
| Date | 2021-04-01 |
| Issue name | Diabetologia |
| Issue number | v64.4:826-835 |
| DOI | 10.1007/s00125-020-05358-3 |
| PubMed | 33474583 |
| Authors | |
| Info | TRIGR Investigators, Mandrup-Poulsen T, Arjas E, Läärä E, Lernmark Å, Schmidt B, Krischer JP, Åkerblom HK, Hyytinen M, Knip M, Koski K, Koski M, Pajakkala E, Salonen M, Cuthbertson D, Krischer JP, Shanker L, Bradley B, Dosch HM, Dupré J, Fraser W, Lawson M, Mahon JL, Sermer M, Taback SP, Becker D, Franciscus M, Nucci A, Palmer J, Virtanen SM, Catteau J, Howard N, Crock P, Craig M, Clarson CL, Bere L, Thompson D, Metzger D, Marshall C, Kwan J, Stephure DK, Pacaud D, Schwarz W, Girgis R, Thompson M, Taback SP, Catte D, Lawson ML, Bradley B, Daneman D, Sermer M, Martin MJ, Morin V, Frenette L, Ferland S, Sanderson S, Heath K, Huot C, Gonthier M, Thibeault M, Legault L, Laforte D, Cummings EA, Scott K, Bridger T, Crummell C, Houlden R, Breen A, Carson G, Kelly S, Sankaran K, Penner M, White RA, King N, Popkin J, Robson L, Al Taji E, Mendlova P, Romanova M, Vavrinec J, Vosahlo J, Brazdova L, Venhacova J, Venhacova P, Cipra A, Tomsikova Z, Paterová P, Gogelova P, Einberg Ü, Riikjärv MA, Ormisson A, Tillmann V, Johansson S, Kleemola P, Parkkola A, Järvenpää AL, Hämäläinen AM, Kiiveri S, Salonen M, Tenhola S, Salonen P, Jason E, Selvenius J, Siljander H, Ylitalo S, Paajanen I, Talvitie T, Lindström K, Huopio H, Pesola J, Veijola R, Tapanainen P, Alar A, Popov E, Virransalo R, Nykänen P, Aschemeier B, Danne T, Kordonouri O, Krikovszky D, Madácsy L, Khazrai YM, Maddaloni E, Pozzilli P, Mannu C, Songini M, de Beaufort C, Schierloh U, Bruining J, Bisschoff M, Basiak A, Wasikowa R, Ciechanowska M, Deja G, Jarosz-Chobot P, Szadkowska A, Cypryk K, Zawodniak-Szalapska M, Castano L, Frutos TG, Oyarzabal M, Serrano-Ríos M, Martínez-Larrad MT, Hawkins FG, Arnau DR, Ludvigsson J, Konefal MS, Hanas R, Lindblad B, Nilsson NÖ, Fors H, Nordwall M, Lindh A, Edenwall H, Åman J, Johansson C, Gadient M, Konrad D, Schoenle E, Becker D, Daftary A, Klein MB, Gilmour C, Palmer J, Malone P, Tanner-Blasiar M, White N, Devaskar U, Horowitz H, Rogers L, Colon R, Frazer T, Torres J, Goland R, Greenberg E, Schachner H, Softness B, Ilonen J, Trucco M, Nichol L, Savilahti E, Härkönen T, Knip M, Vaarala O, Luopajärvi K, Dosch HM |
| Keywords | Beta cell autoimmunity, Childhood growth, Genetic risk, Length, Type 1 diabetes, Weight |
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