Distinct amino acid profile characterizes youth with or at risk for type 2 diabetes

Authors: BACHA, FIDA - Children'S Nutrition Research Center (CNRC); EL-AYASH, HEBA - Children'S Nutrition Research Center (CNRC); MOHAMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC); SHARMA, SUSAN - Children'S Nutrition Research Center (CNRC); PUYAU, MAURICE - Children'S Nutrition Research Center (CNRC); KANCHI, RUPA - Baylor College Of Medicine; COARFA, CRISTIAN - Baylor College Of Medicine

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2024
Publication Date: 4/1/2024
Citation: Bacha, F., El-Ayash, H., Mohamad, M., Sharma, S., Puyau, M., Kanchi, R., Coarfa, C. 2024. Distinct amino acid profile characterizes youth with or at risk for type 2 diabetes. Diabetes. 73(4):628–636. https://doi.org/10.2337/db23-0375.
DOI: https://doi.org/10.2337/db23-0375

Interpretive Summary: Elevation in the concentrations of specific amino-acids (proteins) in the blood has been linked to higher risk of type 2 diabetes in adult individuals. Whether this is the case for youth-onset diabetes is unclear. Researchers in Houston evaluated 127 adolescents (65 of whom were girls) with obesity and with normal weight. Some of the adolescents with obesity had type 2 diabetes or prediabetes. Researchers measured the blood concentrations of amino acids as well as insulin sensitivity and secretion in these youth. They showed that a particular amino acid profile could be detected in youth with prediabetes and type 2 diabetes compared with peers without abnormalities in their glucose regulation. Furthermore, these abnormalities in the circulating amino acids were found to be related to measures of insulin sensitivity and secretion. This suggests that having such abnormality in protein metabolism can be utilized in future studies to identify the youth who are at risk of developing diabetes. This profile can also potentially be used to track the effect of diabetes treatments.

Technical Abstract: Branched-chain amino acids (BCAAs) and aromatic AAs (AAAs) 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 B-cell failure and the development of type 2 diabetes. We performed targeted AA metabolomics analysis on 127 adolescents (65 girls; 15.5 [SD +/-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 of a hyperinsulinemic-euglycemic clamp, with determination of insulin sensitivity (IS) per fat-free mass (FFM). We measured insulin secretion during a 2-h hyperglycemic clamp and calculated the disposition index per FFM (DIFFM), a measure of B-cell function. Our results showed that concentration of glycine (Gly) and the glutamine (Gln)-to-glutamate (Glu) ratio were lower, whereas BCAA, tyrosine, and lysine (Lys) concentrations were higher in the groups with obesity and dysglycemia compared with those with normal weight. Gly and Gln-to-Glu ratio were positively related to IS and DIFFM, with opposite relationships observed for BCAAs, AAAs, and Lys. We conclude that a metabolic signature of low Gly concentration and low Gln-to-Glu ratio, and elevated BCAAs, AAAs, and Lys concentrations may constitute a biomarker to identify youth at risk for B-cell failure.