University of Oulu

Sen, P., Dickens, A.M., López-Bascón, M.A. et al. Metabolic alterations in immune cells associate with progression to type 1 diabetes. Diabetologia 63, 1017–1031 (2020). https://doi.org/10.1007/s00125-020-05107-6

Metabolic alterations in immune cells associate with progression to type 1 diabetes

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Author: Sen, Partho1; Dickens, Alex M.1; Asunción López-Bascón, María2,3;
Organizations: 1Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland
2Department of Analytical Chemistry, University of Córdoba, Córdoba, Spain
3Department of Chemistry, Örebro University, Örebro, Sweden
4Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
5Clinical Microbiology, Turku University Hospital, Turku, Finland
6Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
7Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
8Department of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland
9Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
10Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
11Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
12Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
13Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290, Helsinki, Finland
14Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
15Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
16School of Medical Sciences, Örebro University, Örebro, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020060941244
Language: English
Published: Springer Nature, 2020
Publish Date: 2020-06-09
Description:

Abstract

Aims/hypothesis: Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.

Methods: In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10).

Results: During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.

Conclusions/interpretation: Our data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.

Data availability: The GEMs for PBMCs have been submitted to BioModels (www.ebi.ac.uk/biomodels/), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (https://www.ebi.ac.uk/metabolights/), under accession number MTBLS1015.

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Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 63
Issue: 5
Pages: 1017 - 1031
DOI: 10.1007/s00125-020-05107-6
OADOI: https://oadoi.org/10.1007/s00125-020-05107-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Subjects:
Funding: This study was supported by the Novo Nordisk Foundation (NNF18OC0034506, to MO), Juvenile Diabetes Research Foundation (2-SRA-2014-159-Q-R, to M.O., T.H. and M.K.), Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research – SyMMyS, Decision No. 250114, to MO and MK; and Personalised Health 2014 programme project, Decision No. 292568, to MO and M.K.), and FPU scholarship from the Spanish Ministry of Education, Culture and Sport (FPU15/02373, to MAL-B).
Copyright information: © The Authors 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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