211-LB: Branched-Chain Amino Acid Levels Negatively Associate with Postprandial ß-Cell Function in Type 1 Diabetes

Understanding the role of insulin resistance (IR) in type 1 diabetes (T1D) may help to improve its treatment. Postprandial insulin secretion stimulates amino acid (AA) uptake and protein synthesis. Consequently, impaired insulin-mediated AA clearance could raise postprandial branched-chain AA (BCAA: valine (VAL), leucine (LEU), isoleucine (ILE)) levels and in turn contribute to BCAA-induced IR. We hypothesized that BCAA levels associate negatively with postprandial ß-cell function already in recent-onset T1D. In a cross-sectional study, volunteers of the German Diabetes-Study with T1D (n=10, diabetes duration <1 year) and excellent glycemic control (HbA1C 6.6±0.9%/48±9 mmol/mol), and age-, sex- and BMI- matched glucose tolerant humans (control, CON, n=10, HbA1C 5.1±0.3%/32±3 mmol/mol) underwent a mixed-meal tolerance test (MMT) to assess ß-cell function through disposition index (DI, the product of insulin sensitivity (IS) and acute insulin response to glucose) and postprandial IS (PREDIM index, predicted M-value). Adipose tissue (AT) IR index was calculated as fasting plasma levels of FFA (mmol*l^-1) x insulin (pmol*l^-1). Postprandial total BCAA, VAL and LEU levels were 25% higher in patients with T1D compared with CON (AUC 11167±5136 vs. 8410±3298, 14363±959 vs. 11754±3890, 11980±4317 vs. 8476±4257 µmol*l^-1*3 h^-1, p<0.05, respectively). PREDIM was lower in T1D (3.3±1.1 vs. CON 7.0±1.4 ml*min^-1*m^-2, p<0.01), while fasting and postprandial AT IR were not different. Persons with T1D showed an inverse relationship between BCAA concentrations and C-peptide levels (total BCAA: r=-0.76, p<0.01; VAL: r=-0.80, p<0.01; LEU: r=-0.71, p<0.05; ILE: r=-0.67, p<0.05) and DI (total BCAA: r=-0.71, p<0.05; VAL: r=-0.78, p<0.01; LEU: r=-0.75, p<0.01; ILE: r=-0.69, p<0.05).

In conclusion, persons with even well-controlled recent-onset T1D exhibit elevated postprandial BCAA concentrations, likely due to impaired ß-cell function, which contribute to postprandial IR.