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

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Sen , P , Dickens , A M , Lopez-Bascon , M A , Lindeman , T , Kemppainen , E , Lamichhane , S , Rönkkö , T , Ilonen , J , Toppari , J , Veijola , R , Hyöty , H , Hyötyläinen , T , Knip , M & Oresic , M 2020 , ' Metabolic alterations in immune cells associate with progression to type 1 diabetes ' , Diabetologia , vol. 63 , no. 5 , pp. 1017-1031 .

Title: Metabolic alterations in immune cells associate with progression to type 1 diabetes
Author: Sen, Partho; Dickens, Alex M.; Lopez-Bascon, Maria Asuncion; Lindeman, Tuomas; Kemppainen, Esko; Lamichhane, Santosh; Rönkkö, Tuukka; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta; Hyöty, Heikki; Hyötyläinen, Tuulia; Knip, Mikael; Oresic, Matej
Contributor organization: HUS Children and Adolescents
Children's Hospital
Research Programs Unit
University of Helsinki
CAMM - Research Program for Clinical and Molecular Metabolism
Faculty of Medicine
Date: 2020-05
Language: eng
Number of pages: 15
Belongs to series: Diabetologia
ISSN: 0012-186X
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 (), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (), under accession number MTBLS1015.
Subject: Birth cohort
Genome-scale metabolic modelling
Peripheral blood mononuclear cells
Sphingolipid metabolism
Type 1 diabetes
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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