3_IA_Metabolite_Reversion_Diabetes_Online_Appendix_Rev1.1_Clean.pdf (175.74 kB)
Download filePhospholipid Levels at Seroconversion are Associated with Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young
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posted on 2021-04-16, 16:00 authored by Patrick M. Carry, Lauren A. Vanderlinden, Randi K. Johnson, Teresa Buckner, Oliver Fiehn, Andrea K. Steck, Katerina Kechris, Ivana Yang, Tasha E. Fingerlin, Marian Rewers, Jill M. NorrisReversion of islet
autoimmunity (IA) may point to mechanisms that prevent IA progression. We
followed 199 individuals who developed IA during the Diabetes Autoimmunity Study in the Young. Untargeted metabolomics
was performed in serum samples following IA. Cox-proportional hazards models
were used to test if the metabolites (2,487) predicted IA reversion, two or
more consecutive visits negative for all autoantibodies. We conducted a
principal component analysis (PCA) of the top metabolites, |hazard ratio (HR)
>1.25| and nominal p<0.01. Phosphatidylcholine (16:0_18:1(9Z) was the
strongest individual metabolite (hazard ratio (HR) per 1 standard deviation:
2.16, FDR adjusted p=0.0037). Enrichment
analysis identified four clusters (FDR p<0.10) characterized by an
overabundance of sphingomyelin
(d40:0), phosphatidylcholine (16:0_18:1(9Z)), phosphatidylcholine
(30:0), and L-decanoylcarnitine. Overall, 63 metabolites met the criteria for
inclusion in the PCA. PC1 (HR: 1.4, p<0.0001), PC2 (HR: 0.85, p=0.0185), and
PC4 (HR: 1.28, p=0.0103) were associated with IA reversion. Given the potential
influence of diet on the metabolome, we investigated whether nutrients were
correlated with PCs. We identified 20 nutrients that were correlated with the
PCs (p<0.05). Total sugar intake was the top nutrient. Overall, we
identified an association between phosphatidylcholine, sphingomyelin, and
carnitine levels and reversion of IA.