Serum Indoxyl Sulfate as a Potential Biomarker of Aortic Stiffness in Persons with Type 2 Diabetes Mellitus

<i>Background and Objectives</i>: Indoxyl sulfate (IS), a gut microbiota-derived metabolite of tryptophan, is implicated in vascular dysfunction through oxidative stress and inflammation. This study evaluated the association between serum IS levels and aortic stiffness (AS) in patients with type 2 diabetes mellitus (T2DM). <i>Materials and Methods</i>: This cross-sectional study enrolled 80 patients with T2DM from a medical center in eastern Taiwan, excluding patients with malignancy, acute infection, heart failure, or recent cardiovascular events. Serum IS concentrations were quantified using liquid chromatography-mass spectrometry. AS was assessed using carotid-femoral pulse wave velocity (cfPWV), with values > 10 m/s indicating AS. <i>Results</i>: A total of 30 patients (37.5%) had AS. IS levels were significantly higher in the AS group than in the control group (<i>p</i> < 0.001). After multivariate adjustment, IS remained an independent predictor of AS (odds ratio: 2.565, 95% confidence interval: 1.145-5.748, <i>p</i> = 0.022). Linear regression analysis confirmed IS as an independent contributor to cfPWV values (β = 0.261, <i>p</i> = 0.019). Receiver operating characteristic analysis showed fair discriminatory ability (area under the curve = 0.739, <i>p</i> < 0.001). <i>Conclusions</i>: In patients with T2DM, serum IS is an independent predictor of AS and may serve as a promising nontraditional biomarker for cardiovascular risk stratification.