Identification of pathognomonic purine synthesis biomarkers by metabolomic profiling of adolescents with obesity and type 2 diabetes.

Autor: Concepcion J; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America.; Rady Children's Hospital, San Diego, CA, United States of America., Chen K; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America., Saito R; Keio University, Yamagata, Japan., Gangoiti J; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America., Mendez E; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America., Nikita ME; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America., Barshop BA; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America.; Rady Children's Hospital, San Diego, CA, United States of America., Natarajan L; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States of America., Sharma K; Center for Renal Precision Medicine, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX, Unied States of America., Kim JJ; Department of Pediatrics, University of California San Diego, La Jolla, CA, United States of America.; Rady Children's Hospital, San Diego, CA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Jun 26; Vol. 15 (6), pp. e0234970. Date of Electronic Publication: 2020 Jun 26 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0234970
Abstrakt: The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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