Metabolic Alterations in Human Peripheral Blood Mononuclear Cells Associate with Progression to Islet Autoimmunity and Type 1 Diabetes
Sen, P.; Dickens, A. M.; Lopez-Bascon, M. A.; Lindeman, T.; Kemppainen, E.; Lamichhane, S.; Ronkko, T.; Ilonen, J.; Veijola, R.; Hyoty, H.; Hyotylainen, T.; Knip, M.; Oresic, M.
Show abstract
Previous metabolomics studies suggest that type 1 diabetes (T1D) is preceded by specific metabolic disturbances. Here we asked whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children later developing pancreatic {beta}-cell autoimmunity or overt T1D. In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who either (1) progressed to T1D (PT1D, n=34), (2) seroconverted to [≥]1 islet autoantibody without progressing to T1D (P1Ab, n=27), or (3) remained autoantibody negative during follow-up (CTRL, n=10). During the first year of life, levels of most lipids and polar metabolites were lower in PT1D and P1Ab, versus CTRLs. Pathway overrepresentation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were overrepresented in PT1D. Genome-scale metabolic models of PBMCs in T1D progression were developed using available transcriptomics data and constrained with metabolomics data from our study. Metabolic modeling confirmed altered ceramide pathways as specifically associated with T1D progression.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Vitamin B2 enables peroxisome proliferator-activated receptor α regulation of fasting glucose availability 94%
- Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles at 12 months of age: a population-based cohort study 94%
- Maternal diet-induced obesity during pregnancy alters lipid supply to fetuses and changes the cardiac tissue lipidome in a sex- dependent manner 94%
Similar papers in this journal
- Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes 95%
- Longitudinal pathway analysis using structural information with case studies in early type 1 diabetes 95%
- Identification of metabolomics biomarkers for type 2 diabetes: triangulating evidence from longitudinal and Mendelian randomization analyses 94%
Similar papers in this journal
- Chronic hyperglycaemia drives functional impairment of lymphocytes in diabetic INSC94Y transgenic pigs 95%
- Proteomic and metabolomic signatures associated with the immune response in healthy individuals immunized with an inactivated SARS-CoV-2 vaccine 93%
- Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury 93%
Similar papers in this journal
- Integrated Proteomic and Metabolomic Analyses of the Mitochondrial Neurodegenerative Disease MELAS 92%
- Mammary gland metabolism and its relevance to the fetoplacental expression of cytokine signaling in Caveolin-1 null mice 91%
- Re-mining serum proteomics data reveals extensive post-translational modifications upon Zika and dengue infection 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.