figshare
Browse
Santoshmetabomeeting2020_poster.pdf (1.69 MB)

The circulating metabolites in the progression to islet autoimmunity and type 1 diabetes

Download (1.69 MB)
Version 2 2020-01-21, 18:49
Version 1 2020-01-21, 18:46
poster
posted on 2020-01-21, 18:49 authored by Santosh LamichhaneSantosh Lamichhane, Partho SenPartho Sen, Matej Oresic, Heli Siljander, Heikki Hyöty, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Tuulia Hyötyläinen, Mikael Knip

Type 1 diabetes (T1D) is a chronic autoimmune disease caused by specific destruction of the insulin-producing beta cell. Clinically pre-diabetic period in T1D is characterized by presence of beta cell specific autoantibodies. Earlier metabolomics study suggests specific metabolic disturbances before individuals precede to auto-immunity.

Here, we analyze circulating metabolites in a prospective series of plasma samples from children who progressed to T1D, children who developed islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and matched controls (CTR) in the subset of samples from internationally recognized DIPP and DIABIMMUNE study cohorts. We found sphingomyelins and methionine to be persistently dysregulated in PT1D when compared to the P1Ab and CTR groups. Additionally, bile acids were found to be dysregulated in cases than the CTR during early infancy. We also found potential microbial metabolites including hydroxyphenyllactic acid, indole acetic acid, and 11-eicosenoic acid to be significantly downregulated at early age (3 and 6 months) preceding clinical T1D. Microbial community modelling obtained from the shotgun metagenomics data showed significant differences in microbial metabolic pathways such as fatty acids, L-methionine, bile acids and amino acid biosynthesis among the cases.

Taken together, our study support findings from earlier studies and suggests novel metabolic signatures that characterize children who progressed to islet autoimmunity or overt T1D, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.

Funding

This work was supported by the JDRF (2-SRA-2014-159-Q-R to M.O.), the Novo Nordisk Foundation (no. NNF18OC0034506 to M.O.), Academy of Finland (no. 250114 to M.O.) and Juvenile Diabetes Research Foundation (no. 2-SRA-2014-159-Q-R to M.O.), Academy of Finland postdoctoral grant (No. 323171 to S.L.) and travel suuport from Nordics metabolomics society to S.L.

History