University of Oulu

Lamichhane, S., Kemppainen, E., Trošt, K. et al. Circulating metabolites in progression to islet autoimmunity and type 1 diabetes. Diabetologia 62, 2287–2297 (2019).

Circulating metabolites in progression to islet autoimmunity and type 1 diabetes

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Author: Lamichhane, Santosh1; Kemppainen, Esko1; Trošt, Kajetan2;
Organizations: 1Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520, Turku, Finland
2Steno Diabetes Center Copenhagen, Gentofte, Denmark
3Children’s Hospital, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 11, 00029 HUS, Helsinki, Finland
4Research Program Unit, University of Helsinki, Helsinki, Finland
5Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
6Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
7Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
8Clinical Microbiology, Turku University Hospital, Turku, Finland
9Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
10Department of Pediatrics, Turku University Hospital, Turku, Finland
11Department of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland
12Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
13Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
14Department of Chemistry, Örebro University, Örebro, Sweden
15Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
16Folkhälsan Research Center, Helsinki, Finland
17School of Medical Sciences, Örebro University, 702 81, Örebro, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-03-13


Aims/hypothesis: Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.

Methods: We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.

Results: In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.

Conclusions/interpretation: Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.

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Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 62
Issue: 12
Pages: 2287 - 2297
DOI: 10.1007/s00125-019-04980-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by JDRF grants 4-1998-274, 4-1999-731 4-2001-435 and special research funds for Oulu, Tampere and Turku University Hospitals in Finland. This work was supported by the JDRF (2-SRA-2014-159-Q-R to MO) and the Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research – SyMMyS, decision no. 250114, to MO and MK).
Dataset Reference: The metabolomics data and the associated metadata are deposited at the MetaboLights database [46] with the acquisition number (MTBLS802). All the data supporting the findings of this study are available from the MetaboLights database or from the corresponding authors on reasonable request.
Copyright information: © The Author(s) 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.