Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes : the TEDDY Study

Li, Qian ; Liu, Xiang ; Yang, Jimin ; Erlund, Iris ; Lernmark, Åke LU orcid ; Hagopian, William ; Rewers, Marian ; She, Jin-Xiong ; Toppari, Jorma and Ziegler, Anette-G , et al. (2021) In Diabetes 70(1). p.282-292
Abstract

Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial... (More)

Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.

(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
Diabetes
volume
70
issue
1
pages
11 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:33106256
  • scopus:85099072947
ISSN
1939-327X
DOI
10.2337/db20-0696
language
English
LU publication?
yes
additional info
© 2020 by the American Diabetes Association.
id
0ed9bab1-cae4-4269-a606-390f5f859231
date added to LUP
2020-11-04 08:38:15
date last changed
2024-12-12 19:04:05
@article{0ed9bab1-cae4-4269-a606-390f5f859231,
  abstract     = {{<p>Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.</p>}},
  author       = {{Li, Qian and Liu, Xiang and Yang, Jimin and Erlund, Iris and Lernmark, Åke and Hagopian, William and Rewers, Marian and She, Jin-Xiong and Toppari, Jorma and Ziegler, Anette-G and Akolkar, Beena and Krischer, Jeffrey P}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{282--292}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes : the TEDDY Study}},
  url          = {{http://dx.doi.org/10.2337/db20-0696}},
  doi          = {{10.2337/db20-0696}},
  volume       = {{70}},
  year         = {{2021}},
}