Advanced

First-appearing islet autoantibodies for type 1 diabetes in young children : maternal life events during pregnancy and the child's genetic risk

Johnson, Suzanne Bennett LU ; Lynch, Kristian F LU ; Roth, Roswith ; Lundgren, Markus LU ; Parikh, Hemang M LU ; Akolkar, Beena ; Hagopian, William ; Krischer, Jeffrey ; Rewers, Marian and She, Jin-Xiong , et al. (2021) In Diabetologia 64(3). p.591-602
Abstract

AIMS/HYPOTHESIS: Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk.

METHODS: The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3 months from 3 months to 4 years, and bi-annually thereafter. Reports of major life events during pregnancy... (More)

AIMS/HYPOTHESIS: Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk.

METHODS: The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3 months from 3 months to 4 years, and bi-annually thereafter. Reports of major life events during pregnancy were collected at study inception when the child was 3 months of age and placed into one of six categories. Life events during pregnancy were examined for association with first-appearing insulin (IAA) (N = 222) or GAD (GADA) (N = 209) autoantibodies in the child until 6 years of age using proportional hazard models. Relative excess risk due to interaction (RERI) by the child's HLA-DR and SNP profile was estimated.

RESULTS: Overall, 65% of mothers reported a life event during pregnancy; disease/injury (25%), serious interpersonal (28%) and job-related (25%) life events were most common. The association of life events during pregnancy differed between IAA and GADA as the first-appearing autoantibody. Serious interpersonal life events correlated with increased risk of GADA-first only in HLA-DR3 children with the BACH2-T allele (HR 2.28, p < 0.0001), an additive interaction (RERI 1.87, p = 0.0004). Job-related life events were also associated with increased risk of GADA-first among HLA-DR3/4 children (HR 1.53, p = 0.04) independent of serious interpersonal life events (HR 1.90, p = 0.002), an additive interaction (RERI 1.19, p = 0.004). Job-related life events correlated with reduced risk of IAA-first (HR 0.55, p = 0.004), particularly in children with the BTNL2-GG allele (HR 0.48; 95% CI 0.31, 0.76).

CONCLUSIONS/INTERPRETATION: Specific life events during pregnancy are differentially related to IAA vs GADA as first-appearing IA and interact with different HLA and non-HLA genetic factors, supporting the concept of different endotypes underlying type 1 diabetes. However, the mechanisms underlying these associations remain to be discovered. Life events may be markers for other yet-to-be-identified factors important to the development of first-appearing IA.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
64
issue
3
pages
591 - 602
publisher
Springer
external identifiers
  • pmid:33404683
  • scopus:85098750965
ISSN
1432-0428
DOI
10.1007/s00125-020-05344-9
project
The Environmental Determinants of Diabetes in the Young
language
English
LU publication?
yes
id
b6b5d711-5def-4ebd-850e-a3340409b58d
date added to LUP
2021-01-13 08:40:44
date last changed
2021-06-08 01:23:04
@article{b6b5d711-5def-4ebd-850e-a3340409b58d,
  abstract     = {<p>AIMS/HYPOTHESIS: Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk.</p><p>METHODS: The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3 months from 3 months to 4 years, and bi-annually thereafter. Reports of major life events during pregnancy were collected at study inception when the child was 3 months of age and placed into one of six categories. Life events during pregnancy were examined for association with first-appearing insulin (IAA) (N = 222) or GAD (GADA) (N = 209) autoantibodies in the child until 6 years of age using proportional hazard models. Relative excess risk due to interaction (RERI) by the child's HLA-DR and SNP profile was estimated.</p><p>RESULTS: Overall, 65% of mothers reported a life event during pregnancy; disease/injury (25%), serious interpersonal (28%) and job-related (25%) life events were most common. The association of life events during pregnancy differed between IAA and GADA as the first-appearing autoantibody. Serious interpersonal life events correlated with increased risk of GADA-first only in HLA-DR3 children with the BACH2-T allele (HR 2.28, p &lt; 0.0001), an additive interaction (RERI 1.87, p = 0.0004). Job-related life events were also associated with increased risk of GADA-first among HLA-DR3/4 children (HR 1.53, p = 0.04) independent of serious interpersonal life events (HR 1.90, p = 0.002), an additive interaction (RERI 1.19, p = 0.004). Job-related life events correlated with reduced risk of IAA-first (HR 0.55, p = 0.004), particularly in children with the BTNL2-GG allele (HR 0.48; 95% CI 0.31, 0.76).</p><p>CONCLUSIONS/INTERPRETATION: Specific life events during pregnancy are differentially related to IAA vs GADA as first-appearing IA and interact with different HLA and non-HLA genetic factors, supporting the concept of different endotypes underlying type 1 diabetes. However, the mechanisms underlying these associations remain to be discovered. Life events may be markers for other yet-to-be-identified factors important to the development of first-appearing IA.</p>},
  author       = {Johnson, Suzanne Bennett and Lynch, Kristian F and Roth, Roswith and Lundgren, Markus and Parikh, Hemang M and Akolkar, Beena and Hagopian, William and Krischer, Jeffrey and Rewers, Marian and She, Jin-Xiong and Toppari, Jorma and Ziegler, Anette G and Lernmark, Åke},
  issn         = {1432-0428},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {591--602},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {First-appearing islet autoantibodies for type 1 diabetes in young children : maternal life events during pregnancy and the child's genetic risk},
  url          = {http://dx.doi.org/10.1007/s00125-020-05344-9},
  doi          = {10.1007/s00125-020-05344-9},
  volume       = {64},
  year         = {2021},
}