Branched-Chain Amino Acids Associate Negatively With Postprandial Insulin Secretion In Recent-Onset Diabetes

Context: In addition to unfavorable effects on insulin sensitivity, elevated plasma branched-chain amino acids (BCAA) stimulate insulin secretion, which, over the long-term, could impair pancreatic beta-cell function.Objective: To investigate cross-sectional and prospective associations between circulating BCAA and postprandial beta-cell function in recently diagnosed type 1 and type 2 diabetes.Methods: The study included individuals with well-controlled type 1 and type 2 diabetes (known diabetes duration <12 months) and glucose-tolerant participants (controls) of similar age, sex, and body mass index (n = 10/group) who underwent mixed meal tolerance tests. Plasma BCAA levels were quantified by gas chromatography-mass spectrometry, postprandial beta-cell function was assessed from serum C-peptide levels, and insulin sensitivity was determined from PREDIM index (PREDIcted M-value).Results: In type 1 diabetes, postprandial total BCAA, valine, and leucine levels were 25%, 18%, and 19% higher vs control, and total as well as individual postprandial BCAA were related inversely to C-peptide levels. In type 2 diabetes, postprandial isoleucine was 16% higher vs the respective controls, while neither total nor individual BCAA correlated with C-peptide levels. Whole-body insulin sensitivity was lower in both diabetes groups than in corresponding controls.Conclusion: Insulin deficiency associates with sustained high BCAA concentrations, which could contribute to exhausting the insulin secretory reserve in early type 1 diabetes.