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First-appearing isl...
First-appearing islet autoantibodies for type 1 diabetes in young children : maternal life events during pregnancy and the child's genetic risk
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- Johnson, Suzanne Bennett (författare)
- Florida State University
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- Lynch, Kristian F (författare)
- University of South Florida
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- Roth, Roswith (författare)
- University Hospital Graz
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- Lundgren, Markus (författare)
- Lund University,Lunds universitet,Pediatrisk endokrinologi,Forskargrupper vid Lunds universitet,Paediatric Endocrinology,Lund University Research Groups,Skåne University Hospital
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- Parikh, Hemang M (författare)
- University of South Florida
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- Akolkar, Beena (författare)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Hagopian, William (författare)
- Pacific Northwest Research Institute
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- Krischer, Jeffrey (författare)
- University of South Florida
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- Rewers, Marian (författare)
- University of Northern Colorado
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- She, Jin-Xiong (författare)
- Medical College of Georgia
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- Toppari, Jorma (författare)
- University of Turku,Turku University Hospital
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- Ziegler, Anette G (författare)
- Technical University of Munich,Klinikum rechts der Isar,Helmholtz Zentrum München
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- Lernmark, Åke (författare)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
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- 2021-01-06
- 2021
- Engelska.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 64:3, s. 591-602
- Relaterad länk:
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http://dx.doi.org/10...
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https://link.springe...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Av författaren/redakt...
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Johnson, Suzanne ...
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Lynch, Kristian ...
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Roth, Roswith
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Lundgren, Markus
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Parikh, Hemang M
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Akolkar, Beena
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Hagopian, Willia ...
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Krischer, Jeffre ...
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Rewers, Marian
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She, Jin-Xiong
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Toppari, Jorma
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Ziegler, Anette ...
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Lernmark, Åke
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Diabetologia
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