Background and Objectives: 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. Materials and Methods: 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. Results: Of the 120 participants, 23 (19.2%) had low ABI. Compared with the normal-ABI group, the low-ABI group was older (p = 0.017) and exhibited higher levels of urine albumin-to-creatinine ratio (UACR, p < 0.001), C-reactive protein (CRP, p < 0.001), and TMAO (p < 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; p = 0.003). In Spearman’s rank correlation analyses, log-transformed left ABI (log-left ABI, p = 0.017) and log-right ABI (p = 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; p < 0.001). Conclusions: Among individuals with T2DM, higher serum TMAO levels were associated with lower left and right ABI values and an increased likelihood of PAD.

Background: Peripheral arterial stiffness (PAS) is common in patients with type 2 diabetes mellitus (T2DM). Despite osteopontin (OPN) being linked to structural alterations in the vasculature, its specific association with the cardio-ankle vascular index (CAVI) as an indicator of PAS is still unclear. Methods: A total of 120 patients diagnosed with T2DM were enrolled in this cross-sectional study. Participants were stratified into the PAS group (CAVI ≥ 9.0) and the control group (CAVI < 9.0) based on the diagnostic criterion of CAVI ≥ 9.0. Circulating OPN concentrations were determined via a commercial enzyme-linked immunosorbent assay kit. Results: PAS was present in 72 (60.0%) participants. Relative to the control group, individuals with PAS were older (p < 0.001) and had higher fasting glucose (p = 0.015), glycated hemoglobin (p = 0.006), urine albumin-to-creatinine ratio (p = 0.007), and OPN (p < 0.001) levels, whereas their high-density lipoprotein cholesterol (HDL-C) concentrations were markedly lower (p = 0.021). Spearman’s rank correlation demonstrated a significant positive association between serum OPN concentrations and bilateral CAVI measurements (both p < 0.001). In multivariable Firth logistic regression, elevated serum OPN concentrations were independently predictive of PAS (adjusted odds ratio [aOR] = 1.035; 95% confidence interval [CI]: 1.012–1.066; p = 0.001), along with older age and lower HDL-C levels. These associations were consistent across conventional and penalized logistic regression analyses. Receiver operating characteristic curve analysis revealed that OPN alone achieved an area under the curve (AUC) of 0.748, whereas the model combining OPN, age, and HDL-C achieved an AUC of 0.831. Conclusions: Higher serum OPN levels were independently associated with PAS in patients with T2DM, particularly when combined with age and HDL-C.