1275-P: Higher Branched-Chain Amino Acids in Youth with Type 2 Diabetes Paradoxically Increased by Short-Term Metformin

Abstract

Branched chain amino acids (BCAA) are important signaling molecules that are strongly related to type 2 diabetes (T2D), but the data linking BCAAs to reduced insulin sensitivity (IS) in youth is conflicting. This complex relationship of BCAAs with IS and glycemia may be further confounded by metformin that potentially alters BCAA synthesis and transport via gut mechanisms. Therefore, we compared: (1) BCAAs in 20 youth with T2D pre-metformin to 10 normal glucose tolerant (NGT) age/BMI-matched controls and (2) the change in BCAAs after 3 months of metformin in 8 youth with T2D. Fasting BCAAs were measured with nuclear magnetic resonance spectroscopy and IS and oral disposition index (oDI) calculated during a multi-sample 75g OGTT. Compared to NGT, youth with T2D had higher BCAAs and hemoglobin A1c (HbA1c) but lower IS and oDI (Table). Higher total BCAAs pre-metformin correlated with HbA1c (r=0.6, P<0.001,), inversely correlated with oDI (r= -0.5, P=0.02,), but not with IS or BMI (r=0.2, P>0.2). Metformin decreased HbA1c and increased leucine and isoleucine (Table), but there was no change in BMI, IS or valine (all P>0.05). In youth, higher BCAAs were related to lower β-cell function relative to IS and worse glycemia. Although metformin improved glycemia, BCAAs were paradoxically increased suggesting that BCAAs may not be a useful treatment biomarker or indicator of changes in metabolic status. Disclosure A. Meyers: None. C.K. Cravalho: None. A. Villalobos-Perez: None. S. Matta: None. L. Mabundo: None. A.B. Courville: None. M.L. Sampson: None. J.D. Otvos: Employee; Self; LabCorp. S.T. Chung: None. Funding National Institutes of Health (to S.T.C., L.M., A.B.C.)