The Relationship Between Serum Annexin A5 And Artecial Lesions In Type 2 Diabetic Patients

BackgroundIn recent years,with the rapid development of China's economy,Chinese residents have been eating high-calorie diets such as high-sugar,high-fat,and high-protein for a long time.In addition,the reduction in doing exercise,the morbidity and mortality of diabetes increased significantly and showed a younger trend.In 2017,the International Diabetes Federation(IDF)conducted an epidemiological survey of diabetes worldwide,and found that China has become the country with the largest number of diabetes patients in the world,there are about 114.4 million people,the prevalence rate is 10.9%,and about 840,000 patients die of diabetes every year.Chinese residents spend about 173.4 billion yuan a year on diabetes and its complications,accounting for about 13%of national health care spending.Diabetes mellitus not only does the physical and mental health of our residents greatly threaten,but also patients and society shoulders a huge economic burden.Diabetes mellitus is a metabolic disease characterized by a group of chronic hyperglycemia caused by defects in insulin secretion and/or action,but the pathogenesis of diabetes mellitus is still unclear.More than half of patients with early diabetes do not show any clinical symptoms.Because of this insidious nature,patients have multiple organ or system damage and abnormalities when diagnosed with diabetes complications,which increases the harmf-ulness of diabetes.Chronic complications of diabetes,mainly macrovascular diseases,such as coronary artery disease(CAD)leading to angina or myocardial infarction,peripheral artery disease(PAD)leading to stroke,diabetic encephalopathy and diabetic foot are the first causes of disability and death of diabetes.Atherosclerosis is the main pathological change process of diabetic macroangiopathy,presenting the formation of atherosclerotic plaques in large and medium-sized arteries,arterial wall thickening,stenosis or occlusion,resulting in ischemia or necrosis of tissues or organs supplied by the artery.Compare to non-diabetic patients,diabetic patients are 2-4 times more likely to have cardiovascular disease,and about 65%of diabetic patients die from cardiovascular disease.Therefore,timely screening of diabetic cardiovascular diseases and timely intervention can effectively reduce the incidence of diabetic cardiovascular events.Annexin A5 is one of the most abundant and widely distributed members of the annexin family,and is present in trophoblasts,endothelial cells,macrophages,and monocytes.Its gene is located at 15q21-q22 and consists of 317 amino acids with a relative molecular mass of 36KDa.In recent years,foreign studies have shown that Annexin A5 is associated with the occurrence of vascular AS lesions,which may be due to chronic inflammatory conditions,resulting activation,injury,dying or even apoptosis and necrosis of various types of cells.The asymmetry distribution of the outer phospholipids is broken,mainly because the phosphatidyserine(PS)on the inner side of the phospholipid bilayer membrane is transported to the outer side of the cell membrane,which appears on the surface of the cell,Annexin A5 binding to the PS on the outer side of the cell membrane,the monomeric Annexin A5 assembles to form a two-dimensional crystal,thereby exert anti-inflammatory,anti-apoptotic,anti-coagulation,improving vascular endothelial function and promoting appropriate autophagy.Eventually it hinders the development of vascular atherosclerosis.Some foreign clinical studies had found that serum Annexin A5 AnxA5 is also a promising and emerging cardiovascular biomarker,but the relationship between serum Annexin A5 concentration and vascular atherosclerotic lesions had ino definitive conclusion.Most studies had shown that serum Annexin A5 is negatively correlated with vascular disease,and is an independent biomarker for the diagnosis of angiogenic subclinical atherosclerotic lesions.However,there were different opinions.After adjusted for multiple other cardiovascular risk factors by Burgmaier M,serum Annexin A5 was positively correlated with atherosclerotic lesions.Furthermore,there is little research on serum Annexin A5 and macrovascular atherosclerotic lesions caused by diabetes.Therefore,the relationship between Annexin A5 and atherosclerosis needs further research and confirmation.So,this article explores the relationship between serum Annexin A5 and carotid artery and coronary atherosclerosis in patients with type 2 diabetes,and evaluate the diagnostic value of serum Annexin A5 in the detection of carotid artery and coronary atherosclerosis,in order to provide valuable indicators for the early screening and intervention of diabetic arterial lesions.Chapter 1 Correlation between serum Annexin A5 and carotid atherosclerosis in type 2 diabetic patientsObjective To investigate the correlation between serum Annexin A5 and carotid atherosclerosis in type 2 diabetic patients.method1.A total of 160 patients with T2DM who were admitted to the Department of Endocrinology of the 305th Hospital of the People's Liberation Army from October 2017 to November 2018,including 131 males and 29 females,were all eligible for WHO who published the diagnosis and classification criteria for diabetes;2.The carotid intima-media thickness(CIMT)was measured in T2DM patients enrolled in the study.According to the definition of CIMT,the patients were divided into three groups:51 patients in the normal group(CIMT<1.0mm),50 patients in the thickening group(CIMT>1.0mm),and 59 patients in the plaque group(localized CIMT?1.5mm).Collect general patient information and detect serum Annexin A5;3.All data were analyzed by SPSS22.0 statistical software,and the measurement data was tested by the Shapiro-Wilk test method for normality.Measurement data conforming to the normal distribution were expressed as(x±s).one-way ANOVA was used for comparison between groups,and LSD-t test was used to compare between the two groups.The skewed distribution was measured by median(inter-quartile range)[M(Q)]indicates that the Kruskal-Wallis H test was used for comparison between groups,and the Bonferroni test was used for comparison between the two groups.The enumeration data were tested by x2 test.The correlation analysis was using Spearman correlation analysis.The risk factors of CIMT were analyzed by Binary logistic regression.ROC and AUC were used to evaluate the sensitivity and specificity of serum Annexin A5 in predicting T2DM patients with cervical atherosclerosis.Cohen's kappa coefficient analysis was used to evaluate the consistency of serum Annexin A5 and CIMT in the detection of cervical atherosclerosis.Result1.Comparison of serum Annexin A5 in three groupsThe serum Annexin A5 in the plaque group and the thickening group were lower than that in the normal group[(7.68±1.42)VS(8.67±1.98)VS(10.06±2.49)ng/ml,P<0.05],and the serum Annexin A5 in the thickening group was significantly higher in the plaque group(P = 0.012).2.Correlation analysis of cimt and various indicatorsSpearman correlation analysis showed that CIMT was positively correlated with patient age,duration of diabetes,BMI,HbAlc,TC,and LDL(r = 0.165,0.188,0.184,0.172,0.193,0.179,P<0.05),and HDL and Annexin A5 was negatively correlated(r=-0.167,-0.562,P<0.05);3.Analysis of the influencing factors of CIMTUse CIMT as the dependent variable(category variable assignment:0 is normal,1 is abnormal),other datum were independent variables.serum HDL(OR=0.041,95%CI 1.010?1.102)and Annexin A5(OR=0.654,95%CI 0.515?0.830)were protective factors.Age(OR=1.049,95%CI 1.010?1.102),the course of diabetes(OR=1.149,95%CI 1.028?1.283),HbAlc(OR=1.544,95%CI 1.112?2.143),LDL(OR=1.748,95%CI 1.007?3.036)were risk factors.4.Predictive ability of serum Annexin A5 in carotid vascular disease in patients with type 2 diabetesThe ROC curve of serum Annexin A5 showed an area under ROC of 0.751[95%CI(0.670,0.751)],and the optimal cut-off(Youden Index)was 8.95 ng/ml.The sensitivity was 71.6%and the specificity was 70.6%;The Kappa value of serum Annexin A5 was 0.420[95%CI(0.297,0.561)],indicating that serum Annexin A5 has medium-intensity consistency to diagnose the cervical atherosclerosis.Conclusion1.Serum Annexin A5 is negatively correlated with carotid atherosclerosis in type 2 diabetic patients.It is a protective factor for diabetic angiopathy and may be involved in the development of atherosclerosis in patients with type 2 diabetes.;2.Serum Annexin A5 can be used as a predictor.The index of carotid artery thickening in patients with type 2 diabetes is moderately consistent with the diagnosis of atherosclerosis by carotid ultrasonography.It provides a certain guiding value for early screening of carotid atherosclerosis in patients with type 2 diabetes.Chapter 2 Diagnostic Value of Serum Annexin A5 in Type 2 Diabetes Patients Complicated with Coronary AtherosclerosisObjective To explore the diagnostic value of serum Annexin A5 in with type 2 diabetes with coronary atherosclerosisMethods1.From October 2017 to December 2018,a total of 149 patients with T2DM who underwent coronary angiography due to suspected chest pain or chest tightness or who had been diagnosed with coronary atherosclerotic heart disease,including 110 males,39 females were collected.2.According to the results of coronary angiography,T2DM patients were divided into normal coronary artery and coronary artery disease groups.Calculate corresponding Gensini scores and collect general clinical data,common biomarkers and serum Annexin A5.3.Using SPSS22.0 statistical software for analysis,the measurement data use the Shapiro-Wilk test method for normality test.Measurement data conforming to the normal distribution were expressed as x±s,and Two independent sample t-test was used for comparison between groups.The measurement data of skewed distribution was expressed as median(interquartile range)[M(Q)],comparison between groups uses the Mann-Whitney U test.The enumeration data were tested by X2 test.The correlation analysis was using Spearman correlation analysis.The risk factors of Gensini score were analyzed by Multiple linear regression analysis.ROC and AUC were used to evaluate the sensitivity and specificity of serum Annexin A5 in predicting T2DM patients with coronary atherosclerosis.Cohen's kappa coefficient analysis was used to evaluate the consistency of serum Annexin A5 and Gensini score in the detection of coronary atherosclerosis.Result1.Comparison of serum Annexin A5 between the two groupsSerum Annexin A5 is significantly lower in the coronary artery lesion group than in the normal coronary artery group[(8.18±1.57)VS(10.08±2.47)ng/ml,(P<0.000)].2.Correlation analysis between Gensini score and clinical factorsThe Gensini score is positively correlated with the patient's age,duration of diabetes,BMI,HbA1c and LDL(r = 0.394,0.311,0.202,0.220,0.324,P<0,05),negatively correlates with HDL and Annexin A5(r =-0.236,-0.633,P<0.05).3.Analysis of the influencing factors of Gensini scoreAge,duration of diabetes,serum LDL,HDL and Annexin A5 are independent influencing factors of Gensini score.4.Predictive ability of serum Annexin A5 in carotid vascular disease in patients with type 2 diabetesThe ROC curve of serum Annexin A5 showed an area under ROC of 0.752[95%CI(0.668,0.830)],and the optimal cut-off(Youden Index)was 8.93 ng/ml.The sensitivity was 74.2%and the specificity was 73.1%;The Kappa value of serum Annexin A5 was 0.451[95%CI(0.306,0.596)],indicating that serum Annexin A5 has medium-intensity consistency to diagnose the cervical atherosclerosis.Conclusion1.Serum Annexin A5 is negatively correlated with coronary atherosclerosis in type 2 diabetic patients.It is an independent influencing factor of diabetic angiopathy and may be involved in the development of coronary atherosclerosis in patients with type 2 diabetes;2.Serum Annexin A5 may be As a safer and more sensitive method of examination,coronary angiography with moderate intensity of coronary atherosclerosis may be a new indicator for predicting coronary artery thickening in patients with type 2 diabetes.