Circulating BCKAs are closely associated with adipose tissue insulin resistance in type 2 diabetes

This study aimed to examine the association between branched-chain amino acids/branched-chain α-keto acids (BCAAs/BCKAs) and adipose tissue insulin resistance (Adipo-IR) in patients with type 2 diabetes mellitus (T2DM).

A total of 506 patients with T2DM were included in this cross-sectional study. Participants were categorized into two groups based on Adipo-IR levels (non-Adipo-IR: Adipo-IR<7.68; Adipo-IR: Adipo-IR ≥ 7.68). Serum BCAA/BCKA concentrations were measured using ELISA kits. Correlations between BCAAs/BCKAs and Adipo-IR or HOMA-IR were evaluated using Spearman correlation analysis. Binary logistic regression was used to examine the associations of BCKAs with both indices of insulin resistance.

Median serum BCKA levels were significantly higher in the Adipo-IR group than in the non-Adipo-IR (128.27 vs. 121.16, p < 0.001), while there was no significant difference in median serum BCAA levels between the two groups (2.54 vs. 2.52, p = 0.714). BCKAs were positively correlated with both Adipo-IR and HOMA-IR (both p < 0.01), and the association with Adipo-IR was stronger. Binary logistic regression analysis revealed that BCKAs were associated with Adipo-IR regardless of adjustment for influencing factors, with increasing odds ratios across BCKAs quartiles (p for trend < 0.01). However, after adjusting for covariates, the association between BCKAs and HOMA-IR was no longer significant.

Serum BCKA levels were elevated in T2DM patients with Adipo-IR and were more strongly correlated with Adipo-IR than HOMA-IR. BCKAs may serve as sensitive biomarkers for Adipo-IR. Consequently, we would promote their clinical usage in the early screening of individuals with obesity, insulin resistance and a high risk of T2DM.