Prediabetes Is Associated with Specific Changes in Valine Metabolism

Abstract Objectives Recent studies have suggested that a high plasma concentration of the branched-chain amino acids (BCAAs) can serve as a biomarker for type-2-diabetes (T2D). Whether this is also the case for prediabetes remains unclear. Our goal is to examine whether specific disturbances exist in the kinetics of the BCAAs leucine, isoleucine and valine in middle aged/older adults with prediabetes. Methods We measured BCAA kinetics in 70 prediabetic subjects (fasting glucose: 5.7-6.5 mM), 47 diabetic subjects (fasting glucose: ≥6.5 mM, or are taking medication to control blood glucose) and 170 healthy subjects (fasting glucose: < 5.7 mM) that were 40 years or older. In the fasted state, a pulse of stable isotopes containing leucine, isoleucine and valine was administered intravenously while blood was sampled to assess their whole body production rates (WBP). BCAA tracer enrichment and concentration analyses were done by LC-MS/MS. BCAA whole body production rates were calculated from the area under the curve (AUC). Statistics by ANCOVA corrected for age, sex, and lean body mass as covariates. Significance set at P< 0.05. Results expressed as means [95% CI]. Results The subjects with prediabetes had a lower valine WBP (9492 [8256, 10913] vs. 12288 [11247, 13425] μmol/h, P = 0.0021), but a higher plasma valine concentration (185.7 [176.4, 195.6] vs. 172.2 [166.5, 178.1] μM, P = 0.0178) than the healthy control subjects. No differences in WBP or concentrations of isoleucine or leucine were observed between the groups. Diabetic subjects had the highest plasma concentration for valine across the groups (213.8 [200.4, 228.0] μM, P = < 0.0001), but without a change in the WBP of leucine, isoleucine and valine. Conclusions Prediabetes is characterized by specific changes in the concentration and whole body production of valine. Funding Sources None