Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort

Olga Kordonouri; David Cuthbertson; Malin Belteky; Bärbel Aschemeier-Fuchs; Neil H. White; Elisabeth Cummings; Mikael Knip; Johnny Ludvigsson

doi:10.1007/s00125-022-05786-3

Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort

Olga Kordonouri
, David Cuthbertson
, Malin Belteky
, Bärbel Aschemeier-Fuchs
, Neil H. White
, Elisabeth Cummings
, Mikael Knip
, Johnny Ludvigsson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

12 Citations (Scopus)

17 Downloads (Pure)

Abstract

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. Graphical abstract: [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	2098–2107
Number of pages	10
Journal	Diabetologia
Volume	65
Issue number	12
DOIs	https://doi.org/10.1007/s00125-022-05786-3
Publication status	Published - 2022
Publication type	A1 Journal article-refereed

Funding

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Autoimmunity
Children
Early infections
TRIGR
Type 1 diabetes

Publication forum classification

Publication forum level 2

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

Access to Document

10.1007/s00125-022-05786-3Licence: CC BY

s00125-022-05786-3Final published version, 572 KBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202210217729Licence: CC BY

Cite this

@article{775a88aeea524972af8c0f50443dc882,

title = "Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort",

abstract = "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. Graphical abstract: [Figure not available: see fulltext.]",

keywords = "Autoimmunity, Children, Early infections, TRIGR, Type 1 diabetes",

author = "Olga Kordonouri and David Cuthbertson and Malin Belteky and B{\"a}rbel Aschemeier-Fuchs and White, \{Neil H.\} and Elisabeth Cummings and Mikael Knip and Johnny Ludvigsson",

note = "Funding Information: Open access funding provided by Link{\"o}ping 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 {\textquoteleft}Diabetes Prevention{\textquoteright}). 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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

doi = "10.1007/s00125-022-05786-3",

language = "English",

volume = "65",

pages = "2098–2107",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "12",

}

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. Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

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. Graphical abstract: [Figure not available: see fulltext.]

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. Graphical abstract: [Figure not available: see fulltext.]

KW - Autoimmunity

KW - Children

KW - Early infections

KW - TRIGR

KW - Type 1 diabetes

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 -

Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

Access to Document

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Cite this