Visual Abstract

We studied fasting amino acid levels in 12 children (6 T2D and 6 controls). The mean age was 16.2 ± 0.7 years. The study cohort comprised 42% females, 67% Hispanic, 25% black, and 8% non-Hispanic white. Mean BMI percentile was higher in the T2D group vs. controls (99.1 vs. 50.9 percentiles, p<0.001). In children with T2D, mean HbA1c was 6.4% ± 1% with mean diabetes duration of 1.3 ± 0.3 years. Age, sex, race/ethnicity, the amount of protein intake in the preceding day (61 ± 29 gram), and the duration of fasting (13.5 ± 1 h) were similar between the groups. Fasting citrulline concentration was lower (17.8 vs. 27.8 µmol/L, p=0.01) and fasting ADMA concentration higher (0.523 vs. 0.455 µmol/L, p=0.05) in the children with T2D vs. controls. Fasting arginine level was also lower in the T2D group compared to controls (79.6 vs. 97 µmol/L), but the difference did not attain statistical significance (p=0.22). After Grubb’s test uncovered an outlier in the T2D group, fasting arginine level was also statistically different (69.5 µmol/L in the T2D group vs. 97 µmol/L in controls, p=0.02) (Figure 1). We found a unique metabolomic signature in children with T2D indicating disturbed arginine-citrulline metabolism. Defective arginine-citrulline metabolism may play a role in the pathogenesis of T2D in children, with implications for targeted nutritional therapy.

Disclosure

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

Funding

Texas Children’s Hospital

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