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<0.0for fasting and SS-Gly, SS-Ile, and p=0.02 for SS-Val) and in prediabetes vs. NW (for Gly, Val and Ile) . Fasting and SS-Gly negatively and SS-BCAA positively associated with %body fat, waist/hip, and visceral fat, while Gly positively and BCAA negatively related to adiponectin. Fasting and SS-Gly (r=0.4, p<0.001) positively and SS-BCAA (r=-0.4 for Val, Leu, Ile, p<0.001) negatively related to ISFFM. Gly positively (r=0.27, p=0.005) , SS-Ile (r=-0.26, p=0.006) inversely related to DIFFM. Gly is positively related to IS and β-cell function and negatively to adiposity measures, with opposite relationships observed for BCAA. A metabolic signature of low Gly and elevated BCAA may constitute a biomarker to identify youth at risk for β-cell failure. Disclosure H.El ayash: None. M.A.Mohammad: None. R.S.Shawar: None. R.S.Kanchi: None. S.Sharma: None. M.R.Puyau: None. C.Coarfa: None. F.Bacha: Other Relationship; AstraZeneca, Takeda Pharmaceutical Company Limited, Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Agriculture. Funding USDA-ARS