Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease (1, 2). Chronic complications are the main causes of adverse outcomes in T2DM patients, including blindness, end-stage renal disease, limb amputation, and cardiovascular diseases (3). Among these, cardiovascular diseases are the most severe, being a major cause of disability and death in patients (4). Obstructive sleep apnea hypopnea syndrome (OSAHS) is a clinical syndrome mainly characterized by repeated hypoventilation and respiratory interruption during sleep due to various reasons, resulting in hypoxemia, hypercapnia, and sleep structure disorders (5, 6). As an emerging risk factor for cardiovascular disease, studies have shown that the presence and severity of OSAHS are associated with a higher prevalence of cardiovascular diseases, especially atherosclerosis, hypertension, stroke, and heart failure (7), which severely impacts the quality of life and causing negative effects on both physical and mental health. In recent years, it has gradually attracted attention.

Studies have pointed out that sleep apnea and related hypoxemia can harm the cardiovascular system through mechanisms such as sympathetic nervous system activation, oxidative stress, endothelial dysfunction, systemic inflammation, and lipid peroxidation (8). A meta-analysis by Wang et al. (9) of 12 prospective cohort studies found that, compared to healthy individuals, patients with severe OSAHS had a relative risk of 1.79 for cardiovascular adverse events. Additionally, for every 10-unit increase in AHI, the risk of cardiovascular diseases increased by 17%. A follow-up study conducted by Souza et al. (10) demonstrated that in a cohort with an average age of 48 years, mild, moderate, or severe OSAHS were independently associated with atherosclerosis. However, some researchers believe that OSAHS may not be an independent factor directly causing atherosclerosis. Patients typically exhibit a range of cardiovascular risk factors, which can accelerate the progression of atherosclerosis, even causing vascular lesions in the early stages of the disease (11, 12). A study has shown that T2DM patients with OSAHS develop arteriosclerosis earlier (13). Adderley et al. (14) also proposed that OSAHS in T2DM patients significantly increases the risk of cardiovascular diseases. A longitudinal study spanning 4.9 years on T2DM patients revealed that sleep-disordered breathing predicts adverse cardiovascular events, with a hazard ratio of 1.9 (15). It appears that the coexistence of OSAHS and T2DM seems to have a synergistic effect, elevating the risk of cardiovascular events in these patients. However, some studies have also shown that the association between OSAHS and cardiovascular disease is not strong in T2DM patients (16). A study indicates that, in T2DM patients, although the severity of OSAHS was not significantly associated with adverse cardiovascular events, the cardiovascular disease risk still trends upward in mild OSAHS (17). This study will focus on mild patients, aiming to confirm this increased risk trend so that doctors and patients can identify it earlier and take intervention measures.

Research shows that OSAHS, especially moderate-to-severe OSAHS, is closely related to hypertension (18). Hypoxemia in OSAHS patients triggers excessive activation of the sympathetic nervous system, leading to elevated blood pressure, which induces and accelerates atherosclerosis (19). Therefore, hypertensive patients with OSAHS have a higher risk of adverse cardiovascular events (20). At the same time, hypertension plays a crucial role in T2DM-related complications. Beyond blood glucose control, systolic blood pressure (SBP) has been proven to have independent and additive effects on microvascular and macrovascular complications in T2DM patients (21). Hypertension is likely to mediate, at least to some extent, the relationship between OSAHS and adverse cardiovascular events in T2DM patients, but validation with large sample data is still needed.

Given this, this study proposes the following hypotheses: First, OSAHS may affect arteriosclerosis in T2DM patients, and the arteriosclerosis risk gradually increases with the severity of OSAHS. Secondly, mild OSAHS can also contribute to the arteriosclerosis risk in T2DM patients. Thirdly, the severity of OSAHS may have direct and indirect impacts on arteriosclerosis in T2DM patients, with blood pressure as an intermediary variable in this relationship.

Statistical analysis was performed using R software (version 4.2.0; http://www.R-project.org). The main toolkits include `stats`, `mgcv`, `lmtest`, and `mediation`. Descriptive statistics were used for general clinical data, glucose and lipid metabolism indicators, and sleep-related parameters. Continuous variables were described using means (standard deviation) or medians (interquartile range), and comparisons between groups were made using the t-test or Mann-Whitney U test. Categorical variables were described using frequencies (percentages), and comparisons between groups were made using the χ² test or Fisher’s exact test.

A generalized linear model with a logit link was used to test AHI’s independent and combined effects on the arteriosclerosis status. The predictor of univariate logistic regression analysis was the independent variable AHI, which was used to preliminarily explore its relationship with arteriosclerosis. In the multivariate logistic regression analysis, we used a stepwise adjustment approach: the initial adjustment model incorporated key confounders recognized in the literature (e.g., sex, age, BMI, smoking history, and duration of diabetes); the fully adjusted model was based on the preliminary adjusted model and further included potential confounders that may significantly affect the results (i.e., variables that changed the estimated values ​​of AHI and atherosclerosis risk by more than 10% or were significantly associated with atherosclerosis risk, P <0.1). We calculated unadjusted and adjusted estimates using both exact and asymptotic methods and finally calculated Regression coefficients (β), odds ratios (OR), and their 95% confidence intervals (CI).

A generalized additive model (GAM) was used to fit a smoothed curve for the relationship between AHI and arteriosclerosis, further exploring the nonlinear relationship. Confounders were fully adjusted in the model, and the trend between AHI and arteriosclerosis was observed through curve-fitting results. To evaluate the threshold effect of AHI on arteriosclerosis, this study adopted a segmented logistic regression model and used the log-likelihood ratio test to compare the goodness of fit between two nested models to determine whether an inflection point needed to be introduced. When the P value was significant (P < 0.05), it indicated a significant threshold effect in the model, thus supporting the selection of the segmented model.

A stratified analysis method assessed the interaction between AHI and arteriosclerosis across blood pressure subgroups (hypertension history, SBP, DBP, PP, MAP). The regression coefficients and P values between different subgroups were compared to determine whether significant interaction effects existed.

A mediation effect model was employed to evaluate whether the effect of AHI on arteriosclerosis was indirectly mediated through mediating variables such as blood pressure (SBP, DBP, MAP). The model adjusted for confounding variables such as gender, age, BMI, smoking history, and diabetes duration, then calculated the direct and indirect effects and their proportions. The significance of the mediation effect was tested by the Bootstrap method using the mediation package (version 4.0) of R software, with a sampling frequency of 1000 times, and the percentile method was used to generate the 95% confidence interval of the effect value. All statistical analyses were conducted using a two-sided test, with P < 0.05 considered statistically significant.

Among the 411 T2DM patients included in the study, ages ranged from 18 to 88 years (mean age 52.6 ± 14.9 years), with 276 males (67.2%) and 135 females (32.8%). Based on the criteria for arteriosclerosis, patients were divided into the arteriosclerosis group (299 patients) and the non-arteriosclerosis group (112 patients). Based on AHI, there were 44 patients with simple snoring, 254 with mild-moderate OSAHS, and 113 with severe OSAHS.

This study found a significant association between OSAHS and arteriosclerosis in individuals with T2DM. As the severity of OSAHS increases, the risk of arteriosclerosis also gradually rises. When AHI < 8.8 events/h, the increase in AHI significantly raises the risk of arteriosclerosis, indicating that even a slight elevation of AHI beyond the normal range (5 events/h) may begin to impact arteriosclerosis negatively. The study also revealed that blood pressure indicators mediate the process of OSAHS-related arteriosclerosis. This suggests that the effect of OSAHS on arteriosclerosis is partly exerted through blood pressure, highlighting the importance of actively controlling related risk factors in T2DM patients with OSAHS in clinical practice.

As a common sleep-breathing disorder, OSAHS has gradually attracted widespread attention. Increasing evidence suggests that OSAHS plays a significant role in the occurrence and progression of arteriosclerosis (30–33). OSAHS may disrupt the body’s metabolism and normal physiological rhythms through various pathways such as intermittent hypoxia, sympathetic activation, and the influence on the Hypothalamic-Pituitary-Adrenal (HPA) Axis, thereby advancing the course of arteriosclerosis (34). OSAHS and T2DM often coexist, and the prevalence of OSAHS is significantly higher in patients with T2DM compared to the general population (35). In T2DM patients with OSAHS, macrovascular and microvascular complications increase significantly (36). In a study involving 305 T2DM patients, it was found that AHI was associated with a 2.57-fold increase in stroke risk (37). Research by Adderley and Subramanian (14) showed that T2DM patients who developed OSAHS during follow-up had a significantly higher risk of peripheral neuropathy and atrial fibrillation. A study from the Da Qing Diabetes Research Center also indicated that T2DM patients with OSAHS are more prone to arteriosclerosis, and early intervention is recommended (13). In our study, the AHI and ODI levels were significantly higher in the arteriosclerosis group, indicating more severe sleep apnea and hypoxemia in this group. The results also showed that T2DM patients with atherosclerosis had higher Apo-A1 but lower Apo-B, LDL-C, Apo-B/Apo-A1, and HbA1c. We noted that despite being diagnosed with arteriosclerosis, patients might be at different stages and have received various degrees of treatments, such as a balanced diet, regular exercise, smoking cessation, alcohol restriction, effective glucose, and lipid-lowering treatments, causing observed lipid and glucose metabolism indicators to differ from expectations (38). In the future, we need larger samples, stricter grouping criteria, and more comprehensive variable controls to verify our findings. Further research showed that even mild OSAHS, compared to simple snoring, was associated with arteriosclerosis, and as OSAHS severity increased, so did the risk of arteriosclerosis. Notably, this correlation remains robust in the stratified analysis of different blood pressure indicators, and OSAHS remains an independent risk factor for arteriosclerosis. A study from Beijing indicated that ba-PWV was significantly elevated in T2DM patients with OSAHS, and after adjusting for age, gender, BMI, diabetes duration, blood glucose, blood pressure, blood lipids, and other factors, AHI remained an independent risk factor for increased ba-PWV (33). Drager and Queiroz (39) also found that when diabetes and OSAHS coexist, patients face a higher risk of arteriosclerosis, and the severity of OSAHS correlates with the severity of arteriosclerosis. However, some studies have pointed out that although there is a significant relationship between OSAHS and arteriosclerosis in T2DM patients, the severity of OSAHS is not necessarily related to the severity of arteriosclerosis (40–42). In our study, we did not conduct exhaustive and quantitative monitoring of patients’ dietary habits (such as meal structure, calorie intake, etc.) and medication use (including types, dosages, adherence, etc.), which increases the possibility of generating other unknown confounding effects and may have contributed to differences in the results.

This study also found a threshold effect between AHI and the risk of arteriosclerosis in T2DM patients. Compared to the conventional AHI classification (mild, moderate, severe), the threshold of 8.8 events/h is much lower than the commonly defined upper limit of mild OSAHS (15 events/h). This may suggest that in T2DM patients, even a slight increase in AHI beyond the normal range (5 events/h) could negatively impact arteriosclerosis. This finding highlights the importance of early identification and intervention in patients with mild OSAHS, as it may help reduce the risk of arteriosclerosis and associated cardiovascular events. This is especially important for T2DM patients, as they are already at an increased risk of cardiovascular disease due to diabetes itself. A domestic multicenter prospective study (43) found that T2DM and OSAHS synergistically affect arteriosclerosis. Although the severity of OSAHS was not significantly associated with the risk of major adverse cardiovascular events (MACE), there was an increasing trend of MACE risk in T2DM patients with mild OSAHS, similar to our findings. Severe OSAHS may involve more effective self-protective mechanisms, such as increased breathing or respiratory rate, to compensate for hypoxia, thereby reducing the risk of adverse events (44). A study of 131 T2DM patients found moderate-to-severe OSAHS triples the risk of cardiovascular disease compared to mild or absent OSAHS (17). Some researchers believe that mild OSAHS does not show significant changes in endothelial function and inflammatory indicators and may be considered a confounding variable that needs to be controlled in research (45). Therefore, we look forward to future studies that can further explore this threshold effect and provide a solid evidence base for its application in clinical practice.

In T2DM patients, the potential mechanisms underlying the association between OSAHS and arteriosclerosis are complex. It is still unclear whether OSAHS directly affects arteriosclerosis or exerts its influence indirectly by causing related metabolic disturbances (46). We conducted a mediation analysis to clarify whether AHI affects arteriosclerosis through intermediate variables. The results showed that in T2DM patients, blood pressure indicators mediated the effect of AHI on arteriosclerosis. Although hypertension history and duration also had a mediating effect on the relationship, their impact was not significant. The direct effect of AHI on arteriosclerosis was also insignificant, which may indicate that AHI indirectly influences the increase in arterial stiffness by affecting blood pressure indicators rather than acting directly. OSAHS is closely related to hypertension, with the prevalence of hypertension in OSAHS patients being around 50-60% (47). Hypoxemia and hypercapnia in OSAHS trigger excessive activation of the sympathetic nervous system, and increased sympathetic activity leads to a sharp rise in catecholamine release, increasing cardiac output and peripheral vascular resistance, thereby causing nighttime blood pressure elevation (48). Notably, catecholamine levels in both serum and urine of OSAHS patients rise at night but persist even after the night, during waking periods. This prolonged elevation of catecholamines promotes the development of hypertension in OSAHS patients and is positively correlated with the severity of OSAHS (49, 50). In T2DM patients, hyperglycemia leads to the formation of a large number of advanced glycation end products, triggering oxidative stress, causing vasoconstriction, and contributing to the development of hypertension (51). Hypertension can further damage endothelial cells, increasing insulin resistance, accelerating lipid deposition on the vessel walls, and, through the impact of high-velocity blood flow on the vascular wall, leading to vascular injury and promoting the formation and progression of arteriosclerosis (52). Some experts point out that blood pressure variability, especially changes in SBP, is closely related to arteriosclerosis, and higher variability is associated with increased cardiovascular risk, while average blood pressure levels seem to have a less significant role in this regard (53). Studies have found that when OSAHS coexists with hypertension, there is a cumulative effect on arteriosclerosis, and the association between OSAHS and arteriosclerosis may be mediated by hypertension (54). Siwasaranond et al. (17) expressed a similar view, finding that the risk of arteriosclerosis in T2DM patients with severe OSAHS is 3.05 times higher than in those with mild or no OSAHS, and this relationship is mainly mediated by the presence of hypertension. Clearly, blood pressure control is a critical factor. We recommend personalized blood pressure management plans for T2DM patients with OSAHS through lifestyle interventions, medication adherence, and continuous monitoring with adjustments to the treatment plan as needed. In our study, although all patients were on relatively stable antihypertensive treatment, we did not meticulously document medication use, which may have somewhat obscured the role of blood pressure as a mediating variable. In future research, we can further validate this issue by incorporating ambulatory blood pressure monitoring.

This study has several limitations. First, it is a single-center retrospective study, and there may be selection bias in patient enrollment. Future research should consider expanding the sample scope and verifying it through prospective, multicenter studies to reflect the diversity of the target population more comprehensively. Second, the interactions between OSAHS, T2DM, and arteriosclerosis are complex and multifaceted, so we cannot completely rule out potential residual confounding factors, such as patients’ renal function, lifestyle, and medication use. In future studies, we recommend further incorporating relevant indicators to refine the analysis. Lastly, the study population was limited to T2DM patients, and these results may not broadly represent other populations.

OSAHS significantly impacts arteriosclerosis in T2DM patients, with blood pressure playing a partial mediating role in this process. Early identification and intervention of OSAHS, particularly at the mild OSAHS stage, may help reduce the risk of arteriosclerosis and associated cardiovascular events in T2DM patients, improving overall patient outcomes.