Beclin1 circulating level as predictor of carotid intima-media thickness in patients with type 2 diabetes mellitus

Abstract

Type 2 diabetes (T2DM) represents a major risk factor for atherosclerosis that is the underlying cause of most cardiovascular diseases. Identifying reliable predictive biomarkers are needed to improve the long-term outcome in diabetic patients. Autophagy plays a pivotal role in the pathogenesis of atherosclerosis. Beclin1 is a key regulatory protein of autophagy and has been localized in human atherosclerotic lesions. However, the relation of serum level of Beclin1 and atherosclerosis in patients with diabetes has not been clarified yet. To assess the relationship between serum level of Beclin1 and carotid intima-media thickness (CIMT) in patients with T2DM. In this case-control study participants were recruited from tertiary care hospitals in Egypt. The study enrolled 50 patients with T2DM and 25 healthy subjects between January, 2019 and January, 2020. Age, gender, and body mass index were recorded for all subjects. Laboratory works up including glycated hemoglobin, lipid panel, and serum Beclin1 (by enzyme-linked immunosorbent assay) were measured. CIMT was assessed by color Doppler. Comparisons between patients and the control group were done using analysis of variance and Chi-square test. Correlations between CIMT and Beclin1 level and different variables were done using the Pearson correlation coefficient. Receiver operator characteristic curve was constructed with the area under curve analysis performed to detect the best cutoff value of Beclin1 for detection of CIMT > 0.05 cm. The level of Beclin1 in the patient group was significantly lower compared with that in the control group (1.28 ± 0.51 vs 5.24 ± 1.22 ng/dL, P < .001). The level of Beclin1 apparently decreased in the higher CIMT group in T2DM patients. Serum Beclin1 levels were negatively correlated with CIMT ( r = –0.762; P < .001), low-density lipoprotein-cholesterol ( r = −0.283; P = .04), and triglycerides ( r = −0.350; P = .01) but positively correlated with high-density lipoprotein-cholesterol ( r = 0.491; P < .001) in patients with T2DM. Beclin1 level >2.2 ng/dL was an accurate predictor of CIMT >0.05 cm with an area under the curve value of 0.997, 93.9% sensitivity, and 100% specificity. Beclin1 levels were negatively correlated with atherosclerotic load in patients with T2DM and it may be considered as a promising diagnostic and therapeutic target.

Research progress on the relationship between autophagy and chronic complications of diabetes

“…ATG5 and LC3 are key genes of autophagy and their levels are obviously lower in diabetic nephropathy (DN) model mice than those in normal group, which affects autophagy ( Yassin et al, 2021 ). Autophagy is an essential regulatory mechanism in diabetes, where the serum levels of the ATG protein Beclin-1 are inversely correlated with carotid intima-media thickness in patients with type 2 diabetes (T2D) ( Naguib et al, 2021 ). The hyperglycemic state of diabetic rats increases the accumulation and expression of Beclin-1 simultaneously promoting retinal Müller cell death in rats ( Lopes de Faria et al, 2016 ).…”

Circulating MicroRNA-30a, Beclin1 and Their Association with Different Variables in Females with Metabolically Healthy /Unhealthy Obesity

“…The association between microRNA-30a and cardiovascular diseases has been formerly described. 14 , 32 The microRNA-30 has been shown to affect endothelial cell function and arteriolar branching and consequently development of hypertension. 33 Furthermore, microRNA-30a was found to be associated with an atherogenic lipid profile.…”

“… 33 Furthermore, microRNA-30a was found to be associated with an atherogenic lipid profile. 14 Also, autophagy has important regulatory role in lipid metabolism and autophagy dysfunction is associated with atherogenic lipid profile and development of atherosclerosis. 34 Furthermore, our previous work has demonstrated significant relationship between beclin1 and atherosclerosis and LDL-C, HDL-C, and triglycerides in patients with T2DM.…”

“…Setting the power=0.80 and α=0.05 with using PASS 11th release, 13 each group should have a minimal sample size of three cases to get statistical significance between assumed beclin1 level 1.28±0.51(ng/mL) in patients with type 2 diabetes mellitus (T2DM) and 5.24±1.22(ng/mL) and healthy subjects, respectively. 14 We included 34 women with MHO and 34 women with MUO and 20 healthy controls for further analysis.…”