The global diabetes epidemic poses a significant challenge to public health systems worldwide, imposing considerable economic and social burdens. According to the International Diabetes Federation (IDF) (1), 589 million adults aged 20–79 years are living with diabetes globally. This number is expected to rise to 853 million by 2050, with over 90% of cases attributed to type 2 diabetes mellitus (T2DM). China has the highest diabetes burden, affecting 12.8% of the adult population (2). Crucially, diabetes-related complications, particularly macrovascular diseases such as atherosclerosis, ischemic heart disease, and stroke, have emerged as the leading causes of mortality and disability among patients with diabetes. Importantly, these complications are increasingly prevalent among younger populations (3), underscoring the urgent need for early screening of high-risk individuals and implementation of targeted vascular protection strategies.

Arterial stiffness, characterized by diminished arterial elasticity due to structural and functional abnormalities of the arterial wall, represents an early indicator of atherosclerosis (4). Substantial evidence indicates that increased arterial stiffness is independently correlated with cardiovascular disease (CVD) and renal impairment, serving as a predictor of cardiovascular morbidity and mortality (4–6). Diabetes exacerbates arterial stiffening through various pathophysiological mechanisms, including insulin resistance, endothelial dysfunction, non-enzymatic glycation, platelet dysfunction, chronic inflammation, and increased oxidative stress (7). In patients with T2DM, early detection of arterial stiffness, in conjunction with biomarker identification, is crucial for mitigating the progression of atherosclerosis. Brachial-ankle pulse wave velocity (baPWV), a noninvasive and cost-effective clinical tool, has a strong ability to predict for cardiovascular risk and all-cause mortality in diabetic patients (8, 9). Notably, assessing baPWV in newly diagnosed with T2DM is of significant clinical importance. Many of these patients have already experienced prolonged hyperglycemia, which initiates the progression of vascular stiffness. Early detection of arterial stiffness in this population provides a critical opportunity for intervention, potentially altering the progression of CVD.

Blood urea nitrogen (BUN), a metabolic byproduct of protein catabolism, serves as a biomarker of renal function, nutritional status, and volume status. It has also been independently associated with CVD mortality risk, establishing its utility in the assessment of CVD prognosis (10, 11). Serum albumin(ALB), a key nutritional indicator, critically mediates substance transport, ligand binding, and maintenance of plasma colloid osmotic pressure. Additionally, it has antioxidant, anti-inflammatory, and endothelial stabilizing functions (12, 13). The blood urea nitrogen to serum albumin ratio (BAR) is an innovative biomarker that combines indicators of BUN and ALB, reflecting both nutritional and inflammatory factors. Studies have demonstrated that it has significant predictive value in assessing the prognosis of various diseases, including pneumonia, chronic heart failure, sepsis, and renal insufficiency (14–17). However, its association with arterial stiffness in patients with T2DM remains unknown. Therefore, this study aimed to investigate the correlation between BAR and arterial stiffness, as determined by baPWV, in individuals newly diagnosed with T2DM.

In this study, we investigated the relationship between arterial stiffness, as quantified by baPWV and BAR, in patients newly diagnosed with T2DM. To our knowledge, this study is the first to identify a positive association between BAR and arterial stiffness in T2DM patients, even after adjusting for relevant potential confounders. In each subgroup, the positive association between BAR and baPWV was consistently maintained, as shown by further stratified analyses. Thus, these findings suggest that BAR may be useful in assessing early arterial stiffness in people with T2DM.

Research has consistently shown that there is a significant connection between arterial stiffness and atherosclerotic diseases, including myocardial infarction, heart failure, peripheral vascular disease, and stroke (20–22). Additionally, widespread cardiovascular risk factors such as diabetes, aging, hypertension, obesity, and chronic kidney disease can increase arterial stiffness and decrease elasticity (23). Pulse wave velocity (PWV) is an important index for assessing arterial stiffness and can be characterized by carotid-femoral PWV (cfPWV), brachial-ankle PWV (baPWV), aortic PWV (aPWV), femoral-ankle PWV (faPWV), and carotid-radial PWV (crPWV) according to the pulse wave recording area. Compared with other parameters of arterial stiffness, such as the CAI, CAVI, and CAP, PWV is the most reliable indicator of CVD and is strongly correlated with CVD events and their risk factors, such as hypertension, obesity, and diabetes (9, 24). An increase in arterial stiffness is positively correlated with an increased risk of cardiovascular events and all-cause mortality among T2DM patients (25). The baPWV is a clinically validated, simple, and cost-effective measure for evaluating arterial stiffness. Prospective clinical studies have demonstrated that arterial stiffness, quantified by baPWV, is a predictor of all-cause and cause-specific mortality in individuals with T2DM (8, 26). Research has indicated that an elevated baPWV acts as an independent predictor of adverse prognosis in individuals with ASCVD (27). A 1-SD increase in baPWV raises the likelihood of cardiovascular events by 1.41 times (27). An improvement in arterial stiffness was related to a 43% decrease in the risk of primary composite events, which included stroke, myocardial infarction, and all-cause mortality (28). Research has further indicated that arterial stiffness is an independent risk factor for heart failure. Notably, for every 359 cm/s increase in baPWV, the risk of heart failure increases by 10% over an average period of 5.53 years (20). Recent research has indicated a potential bidirectional connection between the onset of diabetes and arterial stiffness. The Chinese Kailuan Study cohort demonstrated that an increased baPWV significantly elevates the risk of developing diabetes, suggesting that arterial stiffness may act as an early pathological contributor to the development of the disease (29). Further study suggested that aortic stiffness may impair glucose metabolic homeostasis through microvascular damage to the pancreas, liver, and skeletal muscle, potentially serving as an early predictive marker of diabetes (30). Therefore, early assessment of arterial stiffness could be beneficial for predicting T2DM and diabetes-related macrovascular diseases. The identification of simple biomarkers to predict arterial stiffness in clinical settings remains a focal point of research in the field of metabolic diseases.

BUN and ALB are widely used biochemical markers that are easily accessible in routine clinical practice and offer a cost-effective means of assessment. Elevated BUN levels have been shown to be associated with a heightened risk of developing diabetes and its microvascular complications (31, 32), along with a positive, non-linear relationship with the risk of all-cause and cardiovascular mortality in individuals with T2DM (11). Elderly patients with low ALB levels are more likely to have cardiovascular disease, and even those within low-normal ALB level may also be at higher risk of CVD and mortality (33). BAR acts as an indicator of variations in BUN and ALB levels, offering insights into nutritional health, protein metabolism, and the function of the liver and kidney. It serves as an independent predictor of adverse prognosis and short-term mortality in various critical illnesses including pneumonia, sepsis, renal insufficiency, and CVD (14–17, 34–36). Recent studies have identified BAR as a significant prognostic marker of chronic diseases. In a cohort of healthy individuals undergoing physical examinations, a significant positive correlation was identified between BAR and cerebral small vessel disease, including all its subtypes, in a dose-response relationship (37). Moreover, a recent study has identified a significant positive correlation between elevated BAR and increased risks of CVD (OR 1.09), cardiovascular mortality (OR 1.13), and all-cause mortality (OR 1.12) in patients with diabetes (38). In our study, 510 patients with newly diagnosed T2DM were stratified according to BAR tertiles. The group in the highest BAR group presented increased age, blood creatinine and BUN levels. Additionally, the highest BAR group had a greater proportion of patients with arterial stiffness than the other groups. Regardless of whether it was treated as a continuous or categorical variable, BAR was positively correlated with elevated baPWV after adjusting for relevant factors. These findings are consistent with the hypothesis that BAR may interact with various metabolic factors influencing cardiovascular disease and could be a useful marker for the early differentiation of patients with newly diagnosed T2DM with or without arterial stiffness. The stratified analyses indicated that the independent association between the BAR and elevated baPWV in different groups divided by sex and BMI remained consistent. Nevertheless, the limited sample size of the female group may result in imprecise estimated values. These results should be validated in larger, adequately powered studies. Stratified analysis also revealed that the association between BAR and baPWV was more significant in younger patients newly diagnosed with T2DM who were <50 years old. This finding suggests that BAR may be a more prominent correlation factor of arterial stiffness in younger patients with T2DM. Previous studies has been demonstrated that arterial stiffness is more readily improved in young individuals when a healthy lifestyle is adopted (28). In contrast, arterial stiffness in older patients may be influenced by aging, multiple concurrent diseases, and other factors beyond liver and kidney function, thereby potentially explaining the observed attenuation of the association between BAR and baPWV in this subgroup.

The pathophysiological mechanisms connecting BAR and arterial stiffness in individuals with T2DM remain incompletely understood. Previous research has demonstrated a significant association between BAR and type 2 diabetic retinopathy, nephropathy, and macrovascular diseases (17, 38, 39). It was hypothesized that this association was attributable to the effects of the two principal components that constitute BAR. In the hyperglycemic state of T2DM, the body experiences hemodynamic abnormalities, renal function impairment, inflammation, oxidative stress, and endothelial dysfunction. These conditions lead to changes in BUN and ALB levels, promote arterial stiffness, and increase cardiovascular risk and adverse prognosis in patients with diabetes. First, BUN is a critical parameter for evaluating renal function. Elevated BUN levels signify increased protein catabolism and impaired renal function (40). Arterial stiffness and chronic kidney disease may share common pathological pathways that facilitate their co-occurrence and progression (23). The Framingham study established a significant correlation between PWV and the onset of proteinuria (41). Early vascular dysfunction, indicated by a baPWV exceeding the 90th percentile, was significantly associated with proteinuria alone, impaired renal function alone, and the combined risk of proteinuria and renal dysfunction (42). Second, existing research has demonstrated that inflammation is an important factor in the development of diabetes and its related complications (39). Elevated BUN levels have been linked to inflammation, oxidative stress, and compromised endothelial function (43, 44). Urea can induce endoplasmic reticulum stress by inactivating the anti-atherogenic enzyme PGI2 synthase, thereby impairing endothelial function by inhibiting of cell proliferation and inducing endothelial-mesenchymal transition (45, 46). Additionally, urea induces the production of oxygen free radicals from endothelial progenitor cells (EPCs), leading to impaired EPCs function and the development of cardiovascular disease (47). Plasma ALB fulfills several physiological functions, including reducing inflammation, preventing oxidative stress, preservation of vascular endothelial integrity. Research indicates that ALB can attenuate the expression of VCAM-1 induced by TNF-α, thereby inhibiting the onset of vascular inflammation (48). Furthermore, ALB acts as a scavenger of oxygen-free radicals, inhibits the activity of angiotensin-converting enzymes, reduces the sensitivity of blood vessels to nitric oxide, and reduces apoptosis in endothelial cells (49, 50). Finally, elevated BUN levels may serve as indirect markers of a hypercoagulable state, thereby facilitating the onset of diabetic complications. Serum albumin also contributes to the stability of the circulatory system through its anticoagulant, antithrombotic, and antiplatelet aggregation properties (51).

This study encountered various limitations. Firstly, the cross-sectional design of the study precludes the establishment of causal relationships between BAR and baPWV, and the possibility of reverse causality cannot be dismissed. Secondly, despite adjustments for multiple confounding variables, residual confounding, such as that related to lifestyle factors or unmeasured inflammatory markers, may persist. Thirdly, the single-center design and the homogeneous Chinese cohort limit the generalizability of the findings to other populations. Fourthly, the inclusion of only newly diagnosed T2DM patients may restrict the applicability of the results to individuals with a longer disease duration or those undergoing treatment. Finally, the absence of longitudinal data precludes the assessment of BAR’s predictive value for the progression of arterial stiffness. Consequently, it is essential to conduct more prospective randomized controlled trials to substantiate the conclusions of this study.

In conclusion, our findings indicate that BAR is positively and independently associated with arterial stiffness, as determined by baPWV, in Chinese patients with newly diagnosed T2DM. These results imply that BAR levels could play a role in improving the management of cardiovascular complications in patients with newly diagnosed T2DM, particularly those younger than 50 years.