Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk
Anita M Nucci, Suvi M Virtanen, David Cuthbertson, Johnny Ludvigsson, Ulle Einberg, Celine Huot, Luis Castano, Bärbel Aschemeier, Dorothy J Becker, Mikael Knip, Jeffrey P Krischer, TRIGR Investigators, Thomas Mandrup-Poulsen, Elias Arjas, Esa Läärä, Åke Lernmark, Barbara Schmidt, Jeffrey P Krischer, Hans K Åkerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Eeva Pajakkala, Marja Salonen, David Cuthbertson, Jeffrey P Krischer, Linda Shanker, Brenda Bradley, Hans-Michael Dosch, John Dupré, William Fraser, Margaret Lawson, Jeffrey L Mahon, Mathew Sermer, Shayne P Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Suvi M Virtanen, Jacki Catteau, Neville Howard, Patricia Crock, Maria Craig, Cheril L Clarson, Lynda Bere, David Thompson, Daniel Metzger, Colleen Marshall, Jennifer Kwan, David K Stephure, Daniele Pacaud, Wendy Schwarz, Rose Girgis, Marilyn Thompson, Shayne P Taback, Daniel Catte, Margaret L Lawson, Brenda Bradley, Denis Daneman, Mathew Sermer, Mary-Jean Martin, Valérie Morin, Line Frenette, Suzanne Ferland, Susan Sanderson, Kathy Heath, Céline Huot, Monique Gonthier, Maryse Thibeault, Laurent Legault, Diane Laforte, Elizabeth A Cummings, Karen Scott, Tracey Bridger, Cheryl Crummell, Robyn Houlden, Adriana Breen, George Carson, Sheila Kelly, Koravangattu Sankaran, Marie Penner, Richard A White, Nancy King, James Popkin, Laurie Robson, Eva Al Taji, Pavla Mendlova, Martina Romanova, Jan Vavrinec, Jan Vosahlo, Ludmila Brazdova, Jitrenka Venhacova, Petra Venhacova, Adam Cipra, Zdenka Tomsikova, Petra Paterová, Pavla Gogelova, Ülle Einberg, Mall-Anne Riikjärv, Anne Ormisson, Vallo Tillmann, Susanne Johansson, Päivi Kleemola, Anna Parkkola, Anna-Liisa Järvenpää, Anu-Maaria Hämäläinen, Sanne Kiiveri, Maria Salonen, Sirpa Tenhola, Pia Salonen, Eeva Jason, Jenni Selvenius, Heli Siljander, Samuli Ylitalo, Ilkka Paajanen, Timo Talvitie, Kaija Lindström, Hanna Huopio, Jouni Pesola, Riitta Veijola, Päivi Tapanainen, Abram Alar, Erik Popov, Ritva Virransalo, Päivi Nykänen, Bärbel Aschemeier, Thomas Danne, Olga Kordonouri, Dóra Krikovszky, László Madácsy, Yeganeh Manon Khazrai, Ernesto Maddaloni, Paolo Pozzilli, Carla Mannu, Marco Songini, Carine de Beaufort, Ulrike Schierloh, Jan Bruining, Margriet Bisschoff, Aleksander Basiak, Renata Wasikowa, Marta Ciechanowska, Grazyna Deja, Przemyslawa Jarosz-Chobot, Agnieszka Szadkowska, Katarzyna Cypryk, Malgorzata Zawodniak-Szalapska, Luis Castano, Teba Gonzalez Frutos, Mirentxu Oyarzabal, Manuel Serrano-Ríos, María Teresa Martínez-Larrad, Federico Gustavo Hawkins, Dolores Rodriguez Arnau, Johnny Ludvigsson, Malgorzata Smolinska Konefal, Ragnar Hanas, Bengt Lindblad, Nils-Östen Nilsson, Hans Fors, Maria Nordwall, Agne Lindh, Hans Edenwall, Jan Åman, Calle Johansson, Margrit Gadient, Daniel Konrad, Eugen Schoenle, Dorothy Becker, Ashi Daftary, Mary Beth Klein, Carol Gilmour, Jerry Palmer, Patty Malone, Marilyn Tanner-Blasiar, Neil White, Uday Devaskar, Heather Horowitz, Lisa Rogers, Roxana Colon, Teresa Frazer, Jose Torres, Robin Goland, Ellen Greenberg, Holly Schachner, Barney Softness, Jorma Ilonen, Massimo Trucco, Lynn Nichol, Erkki Savilahti, Taina Härkönen, Mikael Knip, Outi Vaarala, Kristiina Luopajärvi, Hans-Michael Dosch, Anita M Nucci, Suvi M Virtanen, David Cuthbertson, Johnny Ludvigsson, Ulle Einberg, Celine Huot, Luis Castano, Bärbel Aschemeier, Dorothy J Becker, Mikael Knip, Jeffrey P Krischer, TRIGR Investigators, Thomas Mandrup-Poulsen, Elias Arjas, Esa Läärä, Åke Lernmark, Barbara Schmidt, Jeffrey P Krischer, Hans K Åkerblom, Mila Hyytinen, Mikael Knip, Katriina Koski, Matti Koski, Eeva Pajakkala, Marja Salonen, David Cuthbertson, Jeffrey P Krischer, Linda Shanker, Brenda Bradley, Hans-Michael Dosch, John Dupré, William Fraser, Margaret Lawson, Jeffrey L Mahon, Mathew Sermer, Shayne P Taback, Dorothy Becker, Margaret Franciscus, Anita Nucci, Jerry Palmer, Suvi M Virtanen, Jacki Catteau, Neville Howard, Patricia Crock, Maria Craig, Cheril L Clarson, Lynda Bere, David Thompson, Daniel Metzger, Colleen Marshall, Jennifer Kwan, David K Stephure, Daniele Pacaud, Wendy Schwarz, Rose Girgis, Marilyn Thompson, Shayne P Taback, Daniel Catte, Margaret L Lawson, Brenda Bradley, Denis Daneman, Mathew Sermer, Mary-Jean Martin, Valérie Morin, Line Frenette, Suzanne Ferland, Susan Sanderson, Kathy Heath, Céline Huot, Monique Gonthier, Maryse Thibeault, Laurent Legault, Diane Laforte, Elizabeth A Cummings, Karen Scott, Tracey Bridger, Cheryl Crummell, Robyn Houlden, Adriana Breen, George Carson, Sheila Kelly, Koravangattu Sankaran, Marie Penner, Richard A White, Nancy King, James Popkin, Laurie Robson, Eva Al Taji, Pavla Mendlova, Martina Romanova, Jan Vavrinec, Jan Vosahlo, Ludmila Brazdova, Jitrenka Venhacova, Petra Venhacova, Adam Cipra, Zdenka Tomsikova, Petra Paterová, Pavla Gogelova, Ülle Einberg, Mall-Anne Riikjärv, Anne Ormisson, Vallo Tillmann, Susanne Johansson, Päivi Kleemola, Anna Parkkola, Anna-Liisa Järvenpää, Anu-Maaria Hämäläinen, Sanne Kiiveri, Maria Salonen, Sirpa Tenhola, Pia Salonen, Eeva Jason, Jenni Selvenius, Heli Siljander, Samuli Ylitalo, Ilkka Paajanen, Timo Talvitie, Kaija Lindström, Hanna Huopio, Jouni Pesola, Riitta Veijola, Päivi Tapanainen, Abram Alar, Erik Popov, Ritva Virransalo, Päivi Nykänen, Bärbel Aschemeier, Thomas Danne, Olga Kordonouri, Dóra Krikovszky, László Madácsy, Yeganeh Manon Khazrai, Ernesto Maddaloni, Paolo Pozzilli, Carla Mannu, Marco Songini, Carine de Beaufort, Ulrike Schierloh, Jan Bruining, Margriet Bisschoff, Aleksander Basiak, Renata Wasikowa, Marta Ciechanowska, Grazyna Deja, Przemyslawa Jarosz-Chobot, Agnieszka Szadkowska, Katarzyna Cypryk, Malgorzata Zawodniak-Szalapska, Luis Castano, Teba Gonzalez Frutos, Mirentxu Oyarzabal, Manuel Serrano-Ríos, María Teresa Martínez-Larrad, Federico Gustavo Hawkins, Dolores Rodriguez Arnau, Johnny Ludvigsson, Malgorzata Smolinska Konefal, Ragnar Hanas, Bengt Lindblad, Nils-Östen Nilsson, Hans Fors, Maria Nordwall, Agne Lindh, Hans Edenwall, Jan Åman, Calle Johansson, Margrit Gadient, Daniel Konrad, Eugen Schoenle, Dorothy Becker, Ashi Daftary, Mary Beth Klein, Carol Gilmour, Jerry Palmer, Patty Malone, Marilyn Tanner-Blasiar, Neil White, Uday Devaskar, Heather Horowitz, Lisa Rogers, Roxana Colon, Teresa Frazer, Jose Torres, Robin Goland, Ellen Greenberg, Holly Schachner, Barney Softness, Jorma Ilonen, Massimo Trucco, Lynn Nichol, Erkki Savilahti, Taina Härkönen, Mikael Knip, Outi Vaarala, Kristiina Luopajärvi, Hans-Michael Dosch
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.
Keywords: Beta cell autoimmunity; Childhood growth; Genetic risk; Length; Type 1 diabetes; Weight.
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Source: PubMed