American Diabetes Association
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Distinct Amino Acid Profile Characterizes Youth with or at risk for Type 2 Diabetes

posted on 2024-01-12, 18:36 authored by Fida Bacha, Heba El-Ayash, Mahmoud Mohamad, Susan Sharma, Maurice Puyau, Rupa Kanchi, Cristian Coarfa

Branched-chain amino acids (BCAA) and aromatic AAs (AAA) are associated with increased risk for type 2 diabetes in adults. Studies in youth show conflicting results. We hypothesized that an AA metabolomic signature can be defined to identify youth at risk for β-cell failure and the development of type 2 diabetes. We performed targeted AA metabolomics analysis on 127 adolescents (65 females, 15.5±1.9 years old, Tanner stage II-V) with normal weight or obesity across the spectrum of glycemia, with assessment of AA concentrations by mass spectrometry, at fasting and steady-state (SS) of a hyperinsulinemic-euglycemic clamp, with determination of insulin sensitivity (ISFFM). We measured insulin secretion during a 2-hour hyperglycemic clamp and calculated the disposition index (DIFFM), a measure of β-cell function. Our results showed that Gly and Gln/Glu were lower, whereas BCAA, Tyr and Lys concentrations were higher in the groups with obesity and dysglycemia compared with those with normal weight. Gly and Gln/Glu were positively related to IS and DIFFM, with opposite relationships observed for BCAA, AAA and Lys. We conclude that a metabolic signature of low Gly, low Gln/Glu and elevated BCAA, AAA and Lys may constitute a biomarker to identify youth at risk for β-cell failure.


This study was supported by the USDA/ARS CRIS Award 3092-51000-057 to FB. The funding source had no involvement in the study design; collection, analysis and interpretation of data; writing of the report; or in the decision to submit the article for publication.


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