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 β-cell function. Objective To investigate cross-sectional and prospective associations between circulating BCAA and postprandial β-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 β-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.