Interaction Between Obesity And HbA1C In Left Ventricular Diastolic Dysfunction In Type 2 Diabetes Mellitus

Backgroud:Diabetic cardiomyopathy is a kind of heart disease that independent of the hypertension and coronary heart disease(CHD),pathophysiology mechanism has not been fully elucidated,the toxicity of sugar,lipotoxicity and insulin resistance is considered to be the main pathogenic pathways.Left ventricular diastolic dysfunction is the earliest functional feature of DCM,which is widely used in the early of DCM.Our team has been working on the study of DCM since 2014,and a small sample(291 cases)of left ventricular diastolic dysfunction in type 2 diabetes mellitus(T2DM)was analyzed,foud that left ventricular diastolic dysfunction was closely related to age,but not statistically related to glycosylated hemoglobin.Based on a large number of relevant literatures at home and abroad,we proposed the scientific hypothesis that the interaction between glycometabolism and obesity may exsit in left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus.Objective:This study was divided into two parts.First,body mass index(BMI)was used as a grouping variable to explore whether the relationship between HbA1c and left ventricular diastolic dysfunction was affected by BMI;Secondly,HbA1c was used as a grouping variable to to investigate whether the relationship between Chinese visceral fat index(CVAI)and left ventricular diastolic dysfunction was based on HbA1c.Methods:925 patients with type 2 diabetes who were hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Shenzhen University from January 2017 to October 2018 were enrolled.All patients were measured for height,weight,waist circumference(WC),glycosylated hemoglobin(HbA1c),blood lipids,calculated BMI、CVAI,and color Doppler echocardiography were performed to assess left ventricular diastolic function.According to the expert consensus standard of comprehensive management of type 2diabetes mellitus with obesity in China in 2016,patients were divided into two groups according to BMI(normal weight group 18.5 kg/m~2<BMI<24 kg/m~2,overweight/obesity group BMI>24 kg/m~2).HbA1c was divided into three groups with 7%and 10%as cut-off points(HbA1c≥10%,7%≤HbA1c<10%,HbA1c<7%).Firstly,the differences of clinical indicators between groups were compared.The study was divided into two parts,firstly,Binary Logistic regression was used to analyze the correlation between HbA1c and left ventricular diastolic function of T2DM;Stratified interaction test was performed to analyze the interaction between HbA1c and BMI in left ventricular diastolic dysfunction,and curve fitting analysis was used to make the trend chart.Finally,a multivariate Cox regression model was used to perform a subgroup analysis of the interaction between HbA1c and BMI,and to compare the role of each randomized combination models in left ventricular diastolic.Secondly,894 patients with type 2 diabetes were selected again for study two,the relationship between WC,BMI,CVAI,and left ventricular diastolic dysfunction was analyzed by binary logistic regression,and the predictive effect of WC,BMI and CVAI was compared according to the area of ROC curve.Then,the interaction of HbA1c and CVAI in left ventricular diastolic dysfunction was analyzed by stratified interaction test,and the trend map was drawn by curve fitting analysis.Results:There was no statistical correlation between HbA1c level and left ventricular diastolic dysfunction in the general population[OR=0.99(0.91,1.08),P=0.8601].Hierarchical analysis according to BMI level showed that HbA1c level was significantly correlated with left ventricular diastolic dysfunction in normal weight group[OR=1.14(1.01,1.30),P=0.0394],but not significantly correlated with overweight/obesity group[OR=0.92(0.82,1.03),P=0.1315].Curve fitting analysis showed that the relationship between HbA1c and left ventricular diastolic dysfunction in T2DM was different in normal weight group and overweight/obesity group.In normal weight group,HbA1c was positively correlated with left ventricular diastolic dysfunction in T2DM with a curve inflection point of about 10%.In overweight/obese group,the risk of left ventricular diastolic dysfunction was significantly increased even at a low level of HbA1c,and the level of HbA1c was negatively correlated with left ventricular diastolic dysfunction.Cox regression model subgroup analysis showed that the risk of left ventricular diastolic dysfunction was negatively correlated with HbA1c level in overweight/obesity group,and was U-shaped in normal weight group.Logistic regression analysis showed that BMI,WC and CVAI were effective predictors of left ventricular diastolic dysfunction in patients with T2DM[WC:OR=1.16(1.08,1.24),P<0.0001],[BMI:OR=1.05(1.03,1.08);P<0.0001],[CVAI:OR=1.02(1.01,1.02),P<0.0001].The following ROC curves of the three groups were analyzed respectively(0.584,0.602,0.683).Stratified analysis showed that CVAI could predict left ventricular diastolic dysfunction in different blood sugar control groups,but the predictive effect decreased with the increase of HbA1c.Conclusion:The correlation between HbA1c and left ventricular diastolic dysfunction was influenced by BMI level.In non-obese state,HbA1c and left ventricular diastolic dysfunction showed a positive curve relationship with saturation threshold(about 10%).In overweight/obesity state,there was a false negative correlation between HbA1c and left ventricular diastolic dysfunction,suggesting that there was a obesity paradox in left ventricular diastolic dysfunction.BMI,WC and CVAI are reliable predictors of left ventricular diastolic dysfunction in type 2 diabetes mellitus.CVAI has the best predictive effect,but the predictive effect is influenced by the interaction of HbA1c.