Serum Trimethylamine N-Oxide Levels Are Associated with Peripheral Artery Disease in Patients with Type 2 Diabetes Mellitus

<i>Background and Objectives</i>: Peripheral arterial disease (PAD), frequently observed in individuals with type 2 diabetes mellitus (T2DM), is associated with diminished life quality, increased cardiovascular risk, and higher mortality rates. Similarly, trimethylamine N-oxide (TMAO), a uremic toxin produced by gut microbiota, has been linked to hypertension, cardiovascular disease, and increased overall mortality. In this study, we aimed to investigate whether serum TMAO levels are related to PAD in T2DM cases. <i>Materials and Methods</i>: In this cross-sectional investigation performed at one medical center, 120 patients with type 2 diabetes mellitus (T2DM) were included. High-performance liquid chromatography-mass spectrometry and an automated oscillometric device were used to measure serum TMAO levels and ankle-brachial index (ABI) values, respectively. Individuals exhibiting an ABI of less than 0.9 were classified as belonging to the low-ABI group. <i>Results</i>: Of the 120 participants, 23 (19.2%) had low ABI. Compared with the normal-ABI group, the low-ABI group was older (<i>p</i> = 0.017) and exhibited higher levels of urine albumin-to-creatinine ratio (UACR, <i>p</i> < 0.001), C-reactive protein (CRP, <i>p</i> < 0.001), and TMAO (<i>p</i> < 0.001). After adjusting for age, UACR, and CRP, multivariable logistic regression analysis identified serum TMAO concentration as an independent predictor of PAD in T2DM patients (odds ratio [OR]: 1.051; 95% confidence interval [CI]: 1.017-1.086; <i>p</i> = 0.003). In Spearman's rank correlation analyses, log-transformed left ABI (log-left ABI, <i>p</i> = 0.017) and log-right ABI (<i>p</i> = 0.001) negatively correlated with log-TMAO. In patients with T2DM, the predictive performance of serum TMAO levels for PAD yielded an area under the receiver operating characteristic (ROC) curve of 0.812 (95% CI: 0.701-0.923; <i>p</i> < 0.001). <i>Conclusions</i>: Among individuals with T2DM, higher serum TMAO levels were associated with lower left and right ABI values and an increased likelihood of PAD.