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

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.