Relationship Between Cardiac Dysfunction Detected By Echocardiography And SRAGE Level In Patients With Type 1 Diabetes Mellitu

Objectives Type 1 diabetes(T1D)is a very common chronic diseases.Diabetic cardiomyopathy(DC)is an important complication of T1 D,which can lead to heart failure.Studies have shown that early echocardiographic abnormalities in patients with T1 D can be manifested not only as left ventricular diastolic dysfunction,but also as early subclinical left ventricular systolic dysfunction.Speckle tracking echocardiography(STE)can track myocardial spots,obtain the position changes between two adjacent frames in the cardiac cycle,so as to calculate the myocardial deformation parameters,which can be used to detect subclinical left ventricular systolic dysfunction in early diabetic cardiomyopathy.Advanced glycation end products(AGEs)are a large class of compounds formed by non enzymatic glycosylation of proteins.At present,the specific types and quantity of AGEs have not been studied clearly yet.Carboxymethyl lysine(CML)and methylglyoxal hydroimidazolone(MG-H)are widely studied in AGEs.They are considered to be related to the pathogenesis of diabetic cardiomyopathy.RAGE,receptor for AGEs,is a receptor on the cell membrane,and is expressed in a variety of cardiac cells,including endothelial cells,vascular smooth muscle cells and myocardial cells.AGEs can directly lead to changes in the function of structural proteins,or interact with RAGE to make cell signal transduction,pro-inflammatory cytokine production,free radical activation,etc.,and eventually lead to the occurrence and development of diabetic cardiomyopathy.In addition to the full-length membrane binding receptor RAGE,soluble RAGE can be detected in the extracellular space and blood circulation.It mainly comes from two ways: the proteolysis of the extracellular part of the full-length RAGE transmembrane receptor,and the alternative splicing of RAGE gene to produce splicing variants.There are at least 19 splicing variants of RAGE gene.Among them,V1 is the only recognized endogenous secret RAGE.Circulating sRAGE can act as a decoy receptor to bind AGE and prevent the adverse effects of AGE on heart directly or indirectly.In previous studies of cardiovascular diseases,sRAGE and esRAGE were also correlated with heart disease status and heart function.The purpose of this study was to detect the changes of cardiac function in early stage of diabetic cardiomyopathy by speckle tracking echocardiography,to determine the circulating levels of CML,MG-H,sRAGE and esRAGE in patients with type 1 diabetes mellitus,and to preliminarily explore the correlation between them and the influencing factors of cardiac dysfunction.MethodsThere were 29 patients with type 1 diabetes and 31 healthy controls.The general clinical data and laboratory indexes were obtained.The concentrations of circulating CML,MG-H,sRAGE and esRAGE were detected by ELISA,and the parameters of cardiac function were obtained by echocardiography.Results1.Compared with the control group,CML was increased and esRAGE decreased in T1 D group,which resulted in the increase of CML / esRAGE ratio.MG-H and sRAGE increased without statistical significance.2.Compared with the control group,the ultrasonic structural parameters of T1 D group,IVSD,LVPWd,LAVI and LVMI was increased,and the differences were statistically significant.Diastolic function parameters: e(lat)decreased,E /e(lat)increased,with statistical significance.In the systolic function parameters,LS in most segments of left ventricle and GLS were lower than those in the control group,and the difference was statistically significant.3.Correlation analysis showed that CML / esRAGE was negatively correlated with diastolic and systolic function,while esRAGE was positively correlated with systolic function.4.Regression analysis showed that CML / esRAGE was the independent determinant of e(lat).The independent determinant of E /e(lat)was heart rate.The independent determinants of GLS were Hb A1 c and duration.Conclusion1.Speckle tracking echocardiography can detect subclinical systolic dysfunction in early stage of diabetic cardiomyopathy,which is more sensitive than left ventricular ejection fraction.Tissue Doppler ultrasound can be used to detect early diastolic dysfunction.2.The decrease of esRAGE may indicate the decrease of systolic function,and the increase of CML / esRAGE may indicate the decrease of systolic or / and diastolic function.3.Good control of blood glucose is still the key to prevent diabetic cardiomyopathy.Patients who have been ill for more than 11 years should routinely monitor cardiac function parameters to detect abnormalities in the early stage.The esRAGE may have a protective effect on cardiac diastolic function.