To investigate arginine metabolism in pediatric T2D, we measured fasting amino acid levels in 28 children (T2D: n=13, healthy controls [H/C]: n=15) . In the T2D group, the mean HbA1c was 8.5 ± 3.4%, with mean diabetes duration of 2.7 ± 2.4 years, and mean BMI percentile higher (98.5 ± 1) than in H/C (71.5 ± 32.6, p=0.006) . There were no statistical differences between T2D and H/C in age (16.4 ± 0.8 years) , sex (46% female) , race/ethnicity (61% Hispanic, 21% Black, 18% non-Hispanic White) , or protein intake in the preceding day (64 ± 30.5 gram) . We found lower fasting arginine (77 ± 21.9 vs. 97.2 ± 15.9 μmol/L, p=0.01) , citrulline (a precursor of arginine) (21.1 ± 7.3 vs. 27.8 ± 5.5 μmol/L, p=0.01) , and glutamine (a precursor of citrulline) (424.6 ± 64.7 vs. 539.5 ± 76.3, p=<0.001) levels in children with T2D vs. H/C. The difference in fasting arginine levels was even more significant (72.6 ± 15.6 in the T2D group vs. 97.2 ± 15.9 μmol/L in controls, p<0.001) after removal of a T2D group outlier identified by Grubb’s test (outlier: 130 vs. the rest: 72.6 ± 15.6 μmol/L) . There were no differences in ornithine, proline, and ADMA levels between the groups (Figure 1) . In conclusion, children with T2D have a unique metabolomic signature in regard to arginine metabolism. Since arginine plays important roles in regulating both insulin secretion and sensitivity, our findings may provide mechanistic insight into T2D pathophysiology and opportunities for precision therapy.


M. Tosur: Advisory Panel; Provention Bio, Inc. S. Deen: None. M.J. Redondo: Advisory Panel; Provention Bio, Inc. F. Jahoor: None. A. Balasubramanyam: None.


Texas Children's Hospital Pilot Grant

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