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

J Endocr Soc. 2021 Apr 20;5(6):bvab067. doi: 10.1210/jendso/bvab067. eCollection 2021 Jun 1.

Abstract

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.

Keywords: BCAA; postprandial insulin secretion; recent-onset diabetes.