348-OR: Glycine and Branched-Chain Amino Acids (BCAA) Metabolic Signature in Youth with Obesity and Type 2 Diabetes (T2D)

BCAAs are associated with increased risk for T2D in adults, while glycine (Gly) appears to be have an inverse relationship. β-cell function is central to the development of T2D in youth. The relationship of Gly and BCAA to β-cell function in youth is not clear. We investigated the relationship between Gly vs. the BCAA: Leucine (Leu) , Isoleucine (Ile) and Valine (Val) , to insulin sensitivity (IS) and β-cell function in youth across the spectrum of glycemia. Adolescents (65 female/62 male; 15.5±1.9 y.o.; 30 with normal weight normal glucose tolerance (NW-NGT) , 33 obese-NGT, 34 prediabetes, and 30 T2D) underwent assessment of AA concentrations (mass spectrometry) , fasting and at steady state (SS) of a 3-hr hyperinsulinemic-euglycemic clamp (in-vivo IS) ; insulin secretion by 2-hr hyperglycemic clamp; adipokines, body composition (DXA) and visceral fat (MRI) . The disposition index (DI) (measure of β-cell function) = first phase insulin x IS per fat free mass (DIFFM) . We performed analysis of variance (adjusting for sex, race-ethnicity and Tanner stage) and correlation analyses. Fasting and SS-Gly were lower and SS-BCAA higher in the groups with obesity compared with NW with post-hoc significant differences in T2D vs. NW (p