University of Oulu

Lamichhane S, Sen P, Dickens AM, Kråkström M, Ilonen J, Lempainen J, Hyöty H, Lahesmaa R, Veijola R, Toppari J, Hyötyläinen T, Knip M and Orešič M (2023) Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children. Front. Endocrinol. 14:1211015. doi: 10.3389/fendo.2023.1211015

Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children

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Author: Lamichhane, Santosh1; Sen, Partho1; Dickens, Alex M.1,2;
Organizations: 1Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland
2Department of Chemistry, University of Turku, University, Turku, Finland
3Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
4Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
5Clinical Microbiology, Turku University Hospital, Turku, Finland
6Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
7Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
8InFLAMES Research Flagship Center, University of Turku, Turku, Finland
9Institute of Biomedicine, University of Turku, Turku, Finland
10Department of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland
11Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
12Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland
13School of Science and Technology, Örebro University, Örebro, Sweden
14Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
15Department of Pediatrics, Tampere University Hospital, Tampere, Finland
16School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.3 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-10-16


Aims/hypothesis: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).

Methods: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.

Results: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.

Conclusion/interpretation: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.

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Series: Frontiers in endocrinology
ISSN: 1664-2392
ISSN-E: 1664-2392
ISSN-L: 1664-2392
Volume: 14
Article number: 1211015
DOI: 10.3389/fendo.2023.1211015
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by the Novo Nordisk Foundation (NNF18OC0034506, to MO), Juvenile Diabetes Research Foundation (2-SRA-2014-159-Q-R, to MO, TH, RL, and MKn), Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research – SyMMyS, Decision No. 250114, to RL, JT, MO, RL, and MKn; and Personalised Health 2014 programme project, Decision No. 292568, to RL, JT, MO, RL, and MKn). Further support was received by the Academy of Finland postdoctoral grant (No. 323171 to SL) and (grant no. 333981 to MO), “Inflammation in human early life: targeting impacts on life-course health” (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under Grant Agreement 101094099 (to MO), the Medical Research Funds, Tampere and Helsinki University Hospitals (to MKn), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530) and Turku University Hospital (to MO, RL, and JT).
Copyright information: © 2023 Lamichhane, Sen, Dickens, Kråkström, Ilonen, Lempainen, Hyöty, Lahesmaa, Veijola, Toppari, Hyötyläinen, Knip and Orešič. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.