Abstract
BACKGROUND: Circulating branched chain amino acids (BCAA) are associated with cardiometabolic risk, although the mechanisms leading to their accumulation remain uncertain. Examining the relationship between fasting status, metabolic syndrome, and type 2 diabetes (T2D) with circulating BCAA levels may provide insights into their metabolic handling. METHODS: We conducted cross-sectional analyses among 25,740 Women's Health Study participants (mean age 55 years). RESULTS: In multivariable linear regression models, fasting was associated with lower plasma BCAAs vs. non-fasting in women without metabolic syndrome or T2D (% mean difference = -5.1%; 95% CI = -5.8, -4.5) and among women with metabolic syndrome only (-3.7%; -4.9, -2.6), p(interaction) = 0.002. However, there was no difference in BCAAs by fasting status among women with T2D (0.4%; -3.7, 4.7). CONCLUSIONS: We observed higher BCAAs with worsening metabolic health status. Fasting is modestly associated with lower plasma BCAAs, except among women with T2D. These findings support hypotheses that impaired BCAA catabolism may be a feature of T2D pathophysiology.