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Diabetologia. 2019 Aug 23. doi: 10.1007/s00125-019-04980-0. [Epub ahead of print]

Circulating metabolites in progression to islet autoimmunity and type 1 diabetes.

Author information

1
Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520, Turku, Finland. santosh.lamichhane@utu.fi.
2
Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520, Turku, Finland.
3
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
4
Children's Hospital, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 11, 00029 HUS, Helsinki, Finland.
5
Research Program Unit, University of Helsinki, Helsinki, Finland.
6
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
7
Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
8
Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
9
Clinical Microbiology, Turku University Hospital, Turku, Finland.
10
Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.
11
Department of Pediatrics, Turku University Hospital, Turku, Finland.
12
Department of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland.
13
Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
14
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
15
Department of Chemistry, Örebro University, Örebro, Sweden.
16
Children's Hospital, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 11, 00029 HUS, Helsinki, Finland. mikael.knip@helsinki.fi.
17
Research Program Unit, University of Helsinki, Helsinki, Finland. mikael.knip@helsinki.fi.
18
Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland. mikael.knip@helsinki.fi.
19
Folkhälsan Research Center, Helsinki, Finland. mikael.knip@helsinki.fi.
20
Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520, Turku, Finland. matej.oresic@utu.fi.
21
School of Medical Sciences, Örebro University, 702 81, Örebro, Sweden. matej.oresic@utu.fi.

Abstract

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.

KEYWORDS:

Beta cell autoimmunity; Metabolomics; Type 1 diabetes

PMID:
31444528
DOI:
10.1007/s00125-019-04980-0

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