Circulating metabolites in progression to islet autoimmunity and type 1 diabetes

循环代谢物在胰岛自身免疫和 1 型糖尿病中的进展

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作者:Santosh Lamichhane, Esko Kemppainen, Kajetan Trošt, Heli Siljander, Heikki Hyöty, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Tuulia Hyötyläinen, Mikael Knip, Matej Orešič

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.

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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