The current study found higher serum and urinary BPA levels in T2DM and diabetic-associated vascular complications groups than in control participants. Also, we found a significant correlation between BPA and vascular calcification biomarkers. In the study groups, serum and urinary BPA levels were negatively correlated with serum and urinary FTA levels. As well as serum and urinary OPG levels were positively increased with serum and urinary BPA levels in the study groups compared to the control group.
Medical calcification is a strong risk factor that develops vascular diseases in diabetes, including diabetes, CVD and DN. In diabetes, increased glucose levels affect the vascular smooth muscle cells (VSMCs) functions, leading to medical calcification [23]. Eraso et al. suggest that lower serum FTA levels were significantly associated with diabetes and its associated vascular complications. In contrast, FTA levels were more significant in diabetes with peripheral arterial disease than in diabetes without peripheral arterial disease patients [24]. These results agree with our study that lower serum and urinary FTA levels were found in T2DM-associated vascular complications groups of CVD and DN compared to T2DM without vascular complications and the control group. Also, serum and urinary FTA negatively correlated with diabetic parameters such as fasting glucose, post-prandial glucose concentration, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). However, our study results contrast with another research study, which found that increased levels of FTA were a risk factor for insulin resistance, ultimately resulting in diabetes [25]. Recently, researchers reported a positive correlation between lower FTA and dyslipidemia [26]. Our study results also showed increased lipid profile levels with lower serum and urinary FTA levels in T2DM, T2DM-associated CVD and DN groups than in the control group.
Another vascular calcification biomarker of OPG was increased in diabetes-associated CVD subjects [27]. Also, serum OPG levels were highly significant with albuminuria in diabetic nephropathy patients [28]. Similarly, our results also resemble the previous research reports. In our study, serum and urinary OPG levels were highly observed in T2DM, T2DM-associated CVD and DN groups than in the control group. Moreover, increased serum and urinary OPG levels were more significant with diabetic parameters such as fasting glucose, post-prandial glucose concentration, HbA1c, and HOMA-IR. Likewise, higher levels of OPG were positively significant with increased lipid profile levels in study participants.
Our results agreed with Talib et al. study, and they found an association between FTA and OPG levels in diabetic nephropathy patients who were under dialysis and resulting lower levels of FTA with increased levels of OPF were observed in T2DM, T2DM-associated CVD and DN groups than in the control group [29]. In our study results, FTA and OPG were negatively associated in study groups. Increased levels of OPG and lower levels of FTA were observed in T2DM, T2DM-associated CVD and DN groups. These results were observed in both serum and urine, respectively.
We also determined that serum and urinary BPA levels were significantly greater in T2DM, T2DM-associated CVD and DN groups than in the control group. There was a positive significant correlation between serum and urinary BPA with fasting glucose, post-prandial glucose concentration, HbA1c and HOMA-IR. Our study results agreed with Soundararajan et al. 2019 study, and they found an association between serum BPA and diabetes parameters such as fasting glucose, post-prandial glucose concentration, HbA1c and HOMA-IR [30]. Also, our study results were revealed by researchers, and they found higher levels of serum BPA in diabetic nephropathy and enhanced urinary BPA levels found in CVD patients compared to control participants [6, 31].
Recent research has evidence that chronic exposure to Bisphenol A alters the carbohydrate and lipid metabolism by affecting the metabolic enzymes, leading to diminishing glucose uptake, which results in diabetes mellitus. According to their findings, BPA enhances the inflammatory response by increasing oxidative stress, which leads to insulin resistance and affects carbohydrate and lipid metabolism [32]. We conclude that diabetic profiling markers such as fasting blood sugar, post-prandial blood sugar and HbA1c were highly significant with serum and urinary BPA levels. Moreover, compared to control groups, increased BPA were found in T2DM and its associated vascular complications. We have evaluated that serum and urinary BPA levels were significantly correlated with increased total cholesterol (TC), triglycerides (TG) and LDL levels. A previous research study observed that enhanced serum BPA levels were highly significant with increased TC concentration and lower HDL cholesterol levels [33].
According to earlier reports, DN and CVD patients had lower FTA levels when compared with control and T2DM subjects [34, 35]. Likewise, our findings suggest that lower levels of FTA result in diabetes, as well as in CVD and DN, when compared with healthy individuals. These lower levels of FTA were directly associated with increased calcification in arteries [36], resulting in diabetes and T2DM with macro and microvascular complications [12]. Our study reported that lower levels of FTA are indirectly proportional to increased serum and urinary BPA levels in T2DM, T2DM-associated CVD and DN groups than in the control group. Previous literature found that higher levels of serum OPG significantly affected cardiac functions [37] and renal functions [38]. Similarly, our results suggest increased serum and urinary OPG levels develop vascular complications in diabetic patients. Also, enhanced OPG levels were observed in diabetes-associated CVD and DN groups compared to T2DM without vascular complications and control groups.
Since it is the first time to investigate the link between BPA and vascular calcification in T2DM patients, we need versatile knowledge about environmental toxins like BPA, which may be probable to cause diabetics-vascular complications which anticipate national and international regulations and guidelines to limit their use and human exposure.