Serum Argininosuccinic Acid Is Associated with Diabetes in Patients with Coronary Artery Disease: An Exploratory Targeted LC–MS/MS Study

Abstract

Diabetes mellitus is associated with metabolic alterations, but amino-acid differences among patients with coronary artery disease (CAD) remain incompletely characterized. We screened 45 amino acids and related metabolites by diabetes status in an exploratory retrospective disease-restricted cohort (recorded diseased-vessel count ≥ 1; n = 33). Argininosuccinic acid was available for 26 patients. Comparisons used exact Wilcoxon tests, Cliff’s delta, and Benjamini–Hochberg correction. Estimated argininosuccinic acid concentrations were higher in diabetes (0.28 [0.21–0.34] vs. 0.15 [0.13–0.19] µmol/L; Cliff’s delta = 0.765; p < 0.001; q = 0.035), the only association surviving false-discovery-rate correction. All argininosuccinic acid estimates were extrapolated below the lowest calibrator and should be interpreted as semiquantitative. The diabetes coefficient remained positive in crude and age- and sex-adjusted HC3-robust models, but renal and influence analyses were imprecise. Argininosuccinic acid correlated inversely with eGFR (rho = −0.445; p = 0.023) and positively with creatinine (rho = 0.486; p = 0.012). The diabetes-by-CAD interaction was not significant (p = 0.183). These data suggest a hypothesis-generating association requiring validation with an appropriate calibration range and careful renal phenotyping.