TY - JOUR
T1 - Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals
T2 - the TRIGR cohort
AU - Kordonouri, Olga
AU - Cuthbertson, David
AU - Belteky, Malin
AU - Aschemeier-Fuchs, Bärbel
AU - White, Neil H.
AU - Cummings, Elisabeth
AU - Knip, Mikael
AU - Ludvigsson, Johnny
N1 - Funding Information:
Open access funding provided by Linköping University. 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, National Institutes of Health, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Further support was provided by the Canadian Institutes of Health Research, the JDRF, the Academy of Finland, a European Foundation for the Study of Diabetes/JDRF/Novo Nordisk focused research grant, and the Commission of the European Communities via the Quality of Life and Management of Living Resources Program (contract number QLK1-2002-00372 ‘Diabetes Prevention’). The content does not necessarily reflect the views of the Commission of the European Communities and in no way anticipates its future policy in this area. The infant formulas used in TRIGR were provided free of charge by Mead Johnson Nutrition.
Funding Information:
We are grateful for the work of all TRIGR investigators (see Appendix in the ESM), and to M. Salonen, Project Coordinator, Biomedicum 2, University of Helsinki, for her outstanding administrative support. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. JL and DC wrote the manuscript, planned the analysis, researched data and contributed to discussion. DC performed the statistical analysis; OK obtained data, initiated and planned the analysis, contributed to the discussion and reviewed/edited the manuscript; MB planned the analysis, contributed to the discussion and reviewed/edited the manuscript. All other authors contributed to acquisition of data, to the discussion and reviewed/edited the manuscript. All authors approved the final version of the manuscript. JL is the guarantor of this work.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Aims/hypothesis: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. Methods: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. Results: Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). Conclusions/interpretation: We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.
AB - Aims/hypothesis: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. Methods: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. Results: Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). Conclusions/interpretation: We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.
KW - Autoimmunity
KW - Children
KW - Early infections
KW - TRIGR
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85137581748&partnerID=8YFLogxK
U2 - 10.1007/s00125-022-05786-3
DO - 10.1007/s00125-022-05786-3
M3 - Article
C2 - 36083343
AN - SCOPUS:85137581748
SN - 0012-186X
VL - 65
SP - 2098
EP - 2107
JO - Diabetologia
JF - Diabetologia
IS - 12
ER -