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