ESPE Yearbook of Paediatric Endocrinology

PLoS One. 2020 Jun 26;15(6):e0234970. doi: 10.1371/journal.pone.0234970.

In brief: Metabolite signatures were compared between children with normal weight, obesity, and both obesity and T2DM, by measuring 273 analytes in fasting plasma and a 24-hour urine sample. Twenty-two urine metabolites were uniquely associated with T2DM. Adolescents with T2DM have altered purine nucleotide metabolism, betaine metabolism, and oxidative branched-chain amino acids (BCAAs) and their catabolites.

Comment: Metabolomics, also known as metabolic profiling, is the systematic study of the unique chemical fingerprints of specific cellular processes (1). It involves the measurement of low-molecular-weight metabolites and their intermediates, and reflects the dynamic response to genetic modification and physiological pathways. Metabolite profiling is also useful in detecting incipient adverse events. The prefix ‘meta’ is Greek and means ‘change’. This study describes a targeted, quantitative mass spectrometry-based approach to generate unique urine and plasma metabolite signatures that differentiate youth with obesity and obesity plus T2DM.

Only a few plasma metabolites were uniquely associated with T2DM. However, a clearer unique signature was demonstrated in urine, in which the purine intermediate succinylaminoimidazole carboxamide riboside (SAICA-riboside) was the most increased. Second were betaine metabolites. The largest set of metabolites in the T2DM urine signature were the BCAAs, valine and leucine, and their direct catabolic derivatives, which were all increased in those with T2DM. Aromatic amino acids (phenylalanine, tyrosine and tryptophan) were also increased in the T2DM group. These findings in adolescents corroborate a prospective study in >4000 adults (2). There, the use of nontargeted metabolomics identified 3 purine metabolites associated with risk of developing T2DM (2). Better understanding of the adverse health effects of each of these metabotoxins is needed. Another study on purines in flies presented below (paper 12.9) may shed some insights.

Reference: 1. Satheesh G, Ramachandran S, Jaleel A. Metabolomics-Based Prospective Studies and Prediction of Type 2 Diabetes Mellitus Risks. Metab Syndr Relat Disord. 2020 Feb;18(1):1–9. doi: 10.1089/met.2019.0047. PMID: 31634052.2. Ottosson F, Smith E, Gallo W, Fernandez C, Melander O. Purine Metabolites and Carnitine Biosynthesis Intermediates Are Biomarkers for Incident Type 2 Diabetes. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4921–4930. doi: 10.1210/jc.2019-00822. PMID: 31502646; PMCID: PMC6804288.