2. Academic Validation
  3. Phospholipid Levels at Seroconversion Are Associated With Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young

Phospholipid Levels at Seroconversion Are Associated With Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young

  • Diabetes. 2021 Jul;70(7):1592-1601. doi: 10.2337/db20-1251.
Patrick M Carry 1,  Lauren A Vanderlinden 1,  Randi K Johnson 2,  Teresa Buckner 1,  Oliver Fiehn 3,  Andrea K Steck 4,  Katerina Kechris 5,  Ivana Yang 6,  Tasha E Fingerlin 1 5 7,  Marian Rewers 4,  Jill M Norris 8 4
Affiliations

Affiliations

  • 1 Department of Epidemiology, Colorado School of Public Health, Aurora, CO.
  • 2 Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • 3 University of California, Davis, Davis, CA.
  • 4 Barbara Davis Center for Diabetes, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • 5 Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO.
  • 6 Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • 7 Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO.
  • 8 Department of Epidemiology, Colorado School of Public Health, Aurora, CO jill.norris@cuanschutz.edu.
PMID: 33863802 DOI: 10.2337/db20-1251
Abstract

Reversion 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 whether the metabolites (2,487) predicted IA reversion: two or more consecutive visits negative for all autoantibodies. We conducted a principal components 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 (HR per 1 SD 2.16, false discovery rate (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.

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