Altered expression of miR-375 and miR-541 in type 2 diabetes patients with and without coronary artery disease (CAD): the potential of miR-375 as a CAD biomarker.

Background: MicroRNAs (miRNAs, miRs) have been linked to beta-cell pathologies and have also shown potential as biomarkers for cardiovascular disease. This study aimed to evaluate the expression of miR-375 and miR-541 in T2D patients with and without CAD, in order to determine the potential of these miRNAs as biomarkers for assessing CAD risk. Methods: This study was conducted on 106 patients with T2D who underwent coronary angiographic examination. Reverse transcription was performed using the cDNA synthesis kit. Real-time PCR was performed using the SYBR Green method and specific primers. The ability to predict which person had developed CAD was evaluated by calculating the area under the receiver-operating characteristic (ROC) curve (AUC). Results: The expression of miR-375 was significantly higher in samples from CAD patients compared to those without CAD (p = 0.009). While the expression of miR-541 was also higher in CAD patients, the difference was not statistically significant. In terms of predicting CAD, miR-375 was found to be a suitable predictor with an AUC of 0.74 (p = 0.01), while miR-541 was not. With a cut-off value of 0.016 for miR-375, the sensitivity was 67% and the specificity was 80%. Conclusion: Our results indicated that circulating levels of miR-375 and miR-541 were elevated in T2D patients with CAD compared to those without CAD. This suggests that miR-375 could potentially be used as a non-invasive biomarker for the diagnosis of CAD in T2D patients.

Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes?

BACKGROUND AND AIMS: Novel biomarkers are required to improve cardiovascular disease prediction in patients with type 2 diabetes (T2D) as a high-risk population. This study was conducted to examine whether coronary artery disease (CAD) risk assessment can be improved by substituting high-density lipoprotein (HDL)-bound paraoxonase 1 (PON1) activity for HDL cholesterol (HDL-C) concentration in patients with T2D. METHODS AND RESULTS: In this study, we studied 139 patients with T2D (mean age 64.12 ± 8.17 years) who underwent coronary angiographic examination. The initial rate of substrate hydrolysis was spectrophotometrically assayed in kinetic mode for measuring PON1 activity. Receiver operating characteristic (ROC) graphs are created by plotting true positivity versus false positivity. In patients with HbA1c ≥ 7%, PON1 (AUC = 0.7, p = 0.029) and nonHDL-C/PON1 (AUC = 0.75, p = 0.013) were significantly more capable of differentiating patients with CAD from those without CAD compared to HDL-C and nonHDL-C/HDL-C. Also, the predictive power of PON1 (AUC = 0.64, p = 0.029) and nonHDL-C/PON1 (AUC = 0.71, p = 0.004) were significantly higher in comparison with HDL-C and nonHDL-C/HDL-C for CAD characterization in patients aged ≥50 years. Moreover, PON1 and nonHDL-C/PON1 are associated with the incidence of CAD with an AUC of 0.7 (p = 0.026) and AUC of 0.64 (p = 0.087), respectively, among subjects with low HDL-C. CONCLUSION: PON1 and the ratio of nonHDL-C/PON1 significantly improve the prediction of severe CAD in T2D patients and in patients with HbA1c ≥ 7%, age ≥50 years, or low HDL-C. PON1 activity and lipid ratios using this enzyme may be valuable as substitutes of HDL-C for increasing clinical efficacies in cardiovascular risk assessment.

The Atherogenic Index Log (Triglyceride/HDL-Cholesterol) as a Biomarker to Identify Type 2 Diabetes Patients with Poor Glycemic Control.

BACKGROUND: Identifying appropriate biomarkers for predicting type 2 diabetes (T2D) patients with increased HbA1c may prove helpful in preventing increased risk of cardiovascular disease (CVD). The present study was conducted to analyze the diagnostic performance of the atherogenic index log (TG/HDL-C) in T2D patients with increased HbA1c. METHODS: Patients with T2D were classified into two groups according to having an HbA1c <8% or ≥8%. Atherogenic index was calculated from the logarithmic transformation of TG/HDL-C. Receiver operating characteristic curve was used to evaluate the diagnostic performance of log (TG/HDL-C). Insulin and fasting glucose concentrations were used to determine homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: Compared with the patients with HbA1c <8%, log (TG/HDL-C) was significantly higher in the patients with HbA1c ≥8% (p = 0.025). The atherogenic index was a biomarker for the prediction of T2D patients with HbA1c ≥8% versus patients with HbA1c <8%, as shown in the area under the curve (AUC = 0.61, P = 0.013). The best cut-off point of log (TG/HDL-C) for the discrimination between patients with HbA1c ≥8% versus patients with HbA1c <8% determined to be 0.44. Atherogenic index was significantly and positively correlated with HOMA-IR in female patients (r = 0.313, P = 0.003) and in patients with an age ≥5o (r = 0.253, P = 0.021). CONCLUSION: The log (TG/HDL-C) in addition to its known association with enhanced CVD risk could be considered as a biomarker to predict T2D patients with poor glycemic control. Therefore, the increased ratio may provide a simple and useful way of identifying poor glycemic T2D patients who are possibly to be at elevated risk of CVD.

Importance of paraoxonase 1 (PON1) as an antioxidant and antiatherogenic enzyme in the cardiovascular complications of type 2 diabetes: Genotypic and phenotypic evaluation.

Oxidant-antioxidant imbalance is involved in the etiology of different diseases, including cardiovascular diseases (CVDs), liver disorders, kidney diseases, cancers and diabetes mellitus. Antioxidant enzymes play a key role in striking an oxidant-antioxidant balance. Moreover, paraoxonase 1 (PON1) is an antioxidant enzyme that binds with high-density lipoprotein (HDL) in the circulation, and antioxidant and antiaterogenic properties of this lipoprotein are significantly associated with PON1. Research suggests PON1 contributes to the pathogenesis of certain human diseases such as type 2 diabetes (T2D). The association between PON1 and T2D appear to be reciprocal so that the disease significantly decreases PON1 levels and in turn, the genetics of PON1 may have a role the risk of susceptibility to T2D. Several factors that reduce the activity and concentration of PON1 in patients with T2D include increased glycation and loss-of-function polymorphisms. The genotypic and phenotypic evaluations of PON1 are therefore crucial for assessing the risk of cardiovascular complications in these patients, and strategies for increasing or restoring PON1 levels are useful for reducing or preventing their cardiovascular complications as their main cause of mortality. The present review aimed at discussing and emphasizing the key role of PON1 in T2D as a silent and dangerous disease.