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 and Objectives: 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). Materials and Methods: 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. Results: A total of 30 patients (37.5%) had AS. IS levels were significantly higher in the AS group than in the control group (p < 0.001). After multivariate adjustment, IS remained an independent predictor of AS (odds ratio: 2.565, 95% confidence interval: 1.145–5.748, p = 0.022). Linear regression analysis confirmed IS as an independent contributor to cfPWV values (β = 0.261, p = 0.019). Receiver operating characteristic analysis showed fair discriminatory ability (area under the curve = 0.739, p < 0.001). Conclusions: In patients with T2DM, serum IS is an independent predictor of AS and may serve as a promising nontraditional biomarker for cardiovascular risk stratification.

Background/Objectives: Endothelial dysfunction represents an early stage of vascular injury in type 2 diabetes mellitus (T2DM) and contributes to increased cardiovascular risk. Leptin, a hormone involved in metabolic and inflammatory regulation, has been implicated in vascular dysfunction. However, its association with digital thermal monitoring (DTM)-derived peripheral vascular reactivity in T2DM remains unclear. Methods: This cross-sectional study enrolled 88 patients with T2DM to investigate the association between serum leptin levels and peripheral vascular reactivity, assessed using the digital thermal monitoring-derived vascular reactivity index (VRI). Based on the VRI values, patients were categorized as having good (VRI ≥ 2.0), intermediate (VRI of 1.0–1.9), or poor (VRI < 1.0) vascular reactivity. Serum leptin levels were quantified using an enzyme immunoassay. Results: Patients with poor vascular reactivity were older and had higher total cholesterol, triglyceride, fasting glucose, glycated hemoglobin, urine albumin-to-creatinine ratio, and leptin levels. In the primary parsimonious multivariable logistic regression model adjusted for age, sex, body mass index (BMI) and eGFR, higher serum leptin levels were associated with vascular reactivity dysfunction. Linear regression analysis also showed that log-transformed leptin levels were negatively associated with VRI. Exploratory analyses, including poor vascular reactivity models and penalized regression models, showed generally consistent findings but were interpreted cautiously because of the limited number of outcome events. Conclusions: Higher serum leptin levels were associated with impaired DTM-derived peripheral vascular reactivity in clinically stable patients with T2DM after adjustment for age, sex, BMI, and eGFR. These findings should be interpreted cautiously and require validation in larger prospective studies.

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.

Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM.