| ObjectiveThe aim of this study is to analyze the effects of dapagliflozin on vascular endothelial function and atherosclerotic indexes in overweight or obese type 2diabetes mellitus(T2DM)patients,to investigate the factors affecting their vascular endothelial function and atherosclerotic indexes,and to further clarify the early cardiovascular protective effects of dapagliflozin in overweight or obese T2 DM patients.MethodsIn this study,patients who met the diagnostic criteria of overweight or obesity and T2 DM in the inpatient and outpatient departments of the First Hospital of Lanzhou University from December 2018 to December 2020 were collected as study subjects,and cases were screened according to inclusion and exclusion criteria,and cases treated with oral dapagliflozin 10mg/day for 6 months were as the dapagliflozin group(n=68),cases not treated with dapagliflozin were as the control group(n=75).Patients in both groups were given diabetic diet,metformin and insulin treatment.This study collected many data in detail before and after 6 months in both groups,including: general clinical data,glucolipid metabolic indexes,endothelial function indexes: nitroglycerin-mediated non-endothelium-dependent vasodilation(NMD),brachial flow-mediated endothelium-dependent vasodilation(FMD)and vascular sclerosis indexes: brachial ankle pulse wave velocity(ba PWV),carotid intima-media thickness(CIMT)and ankle-brachial index(ABI).The changes of before and after treatment in general clinical data,glucose and lipid metabolism indexes,endothelial function indexes and atherosclerosis indexes were analyzed by paired-sample t-test;the differences between the two groups in glucose and lipid metabolism indexes,endothelial function and atherosclerosis indexes were analyzed using independent-sample t-test;spearman correlation analysis and multiple linear regression analysis were used to explore the effects of obesity or obese T2 DM endothelial function indexes(FMD,NMD)and atherosclerotic indexes(ba PWV,CIMT,ABI)associated factors.Results1.Comparison of the base data of the enrolled patients showed that there was no statistically significant differences between the two groups in terms of duration of diabetes,gender,age,weight,BMI,HR,SBP,DBP,hsCRP,insulin TDD(insulin total daily dose),FBG,2h PG,Hb A1 c,FINS,TG,TC,LDL-C,HDL-C(p>0.05).2.After 6 months,weight,BMI,hsCRP,SBP and TDD in the dapagliflozin group were lower than the control group,and the differences were statistically significant(p<0.05);FBG,2h PG,Hb A1 c,TC,LDL-C in the dapagliflozin group were lower than baseline,and the differences were statistically significant(p<0.05).3.Comparison of vascular endothelial function indexes before and after treatment between two groups of patients(1)No statistical difference was seen between the baseline comparison of FMD and NMD in the dapagliflozin group and the control group(p>0.05);(2)After 6 months,FMD was significantly higher in the dapagliflozin group(6.55±2.63%)than in the control group(5.35±2.14%),with statistically significant differences(p<0.05);however,no statistically significant differences were seen in NMD(p>0.05);(3)FMD in the dapagliflozin group(6.55±2.63%)was significantly higher than the baseline level(4.63±1.80%)compared to the pre-observation baseline,with a statistically significant difference(p<0.05);no statistically significant difference was seen in NMD compared to baseline(p>0.05).4.Comparison of atherosclerotic indexes before and after treatment between the two groups(1)There was no statistical difference in CIMT,ba PWV and ABI between the dapagliflozin group and the control group at baseline(p>0.05);(2)After 6 months,ba PWV(1337±116cm/s)in the dapagliflozin group was lower than that in the control group(1408±137cm/s),and the difference was statistically significant(p<0.05);there was no statistically significant differences in ABI and CIMT between groups(p>0.05);(3)Compared with the pre-observation baseline,ba PWV in the dapagliflozin group(1337±116cm/s)was significantly lower than the baseline level(1488±140cm/s),and the difference was statistically significant(p<0.05);no statistically significant differences were seen in the comparison in CIMT and ABI between groups(p>0.05).5.Univariate correlation analysis of vascular endothelial function indices in patients with overweight or obese T2DM(1)FMD was positively correlated with dapagliflozin(r=0.216,p=0.001)and negatively correlated with gender,BMI,Hb Alc,SBP,hsCRP(r=-0.020,p=0.026;r=-0.193,p<0.001;r=-0.167,p<0.001;r=-0.045,p<0.001;r=-0.211,p<0.001);(2)NMD was negatively correlated with BMI and SBP(r=-0.471,p<0.001;r=-0.334,p<0.001).6.Univariate correlation analysis of atherosclerotic indexes in patients with overweight or obese T2DM(1)ba PWV was positively correlated with gender,age and hsCRP(r=0.012,p<0.05;r=0.025,p<0.05;r=0.164,p<0.05);and ba PWV was negatively correlated with dapagliflozin(r=-0.201,p<0.001);(2)ABI was positively correlated with LDL-C(r=0.166,p<0.05);(3)CIMT was positively correlated with BMI and SBP(r=0.235,p<0.001;r=0.232,p<0.05).7.Linear regression analysis of factors influencing endothelial function and atherosclerosis in patients with overweight or obese T2DM(1)Dapagliflozin use was a protective factor for FMD(β=0.032,p<0.05);hsCRP was an independent risk factor for FMD(β=-0.025,p<0.001)and SBP was an independent risk factor for NMD(β=-0.047,p<0.001);(2)Dapagliflozin use was a protective factor for ba PWV(β=-0.227,p<0.001),hsCRP,BMI and SBP were independent risk factors for ba PWV(β=0.084,p=0.032;β=0.066,p=0.029;β=0.039,p=0.017),and hsCRP was an independent risk factor for ABI(β=-0.026,p=0.014).ConclusionDapagliflozin exerts hypoglycemic,antihypertensive,weight-loss and lipid-lowering effects,and also has a certain improvement effect on endothelial cell function and atherosclerosis in patients with overweight or obese T2 DM.The inflammatory factor hsCRP is an independent risk factor for endothelial function and atherosclerosis in patients with overweight or obese T2DM. |
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