| 达格列净对超重或肥胖T2DM患者血管内皮功能和动脉硬化影响的研究 |
| Alternative Title | STUDY ON THE EFFECTS OF DAPAGLIFLOZIN ON VASCULAR ENDOTHELIAL FUNCTION AND ATHEROSCLEROSIS IN OVERWEIGHT OR OBESE TYPE 2 DIABETIC PATIENTS
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| 李倩 |
| Subtype | 硕士
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| Thesis Advisor | 吕海宏
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| 2021-05-20
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| Degree Grantor | 兰州大学
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| Place of Conferral | 兰州
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| Degree Name | 医学硕士
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| Degree Discipline | 内科学
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| Keyword | 达格列净
超重
肥胖
T2DM
血管内皮
动脉硬化
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| Abstract | 中文摘要
目的：
本研究探究达格列净对超重或肥胖2型糖尿病（T2DM）患者血管内皮功能和动脉硬化指标的影响，分析影响其血管内皮功能和动脉硬化指标相关因素，进一步明确达格列净对超重或肥胖T2DM患者心血管早期保护作用。
方法：
本研究收集2018年12月-2020年12月兰州大学第一医院住院部及门诊部符合超重或肥胖及T2DM诊断标准的患者作为研究对象，根据纳入及排除标准筛选病例并分为两组，达格列净组（n=68）为口服达格列净10mg/日、疗程持续6个月者;对照组（n=75）为未使用达格列净治疗者。两组患者均给予糖尿病饮食、二甲双胍及胰岛素治疗。详细采集两组患者6个月前后的一般临床资料、糖脂代谢指标、内皮细胞功能指标：硝酸甘油介导非内皮依赖性血管舒张功能（NMD）、肱动脉血流介导内皮依赖性血管舒张功能（FMD）及血管硬化指标：臂踝脉搏波速度（baPWV）、颈动脉内膜中层厚度（CIMT）及踝肱指数（ABI）;使用配对样本T检验分析研究对象治疗（试验）前后一般临床资料、糖脂代谢指标、内皮功能指标及动脉硬化指标的变化，采用独立样本T检验分析两组患者糖脂代谢指标、内皮功能及动脉硬化指标差异，采用Spearman相关性分析及多重线性回归分析探讨影响超重或肥胖T2DM内皮功能指标（FMD、NMD）及动脉硬化指标（baPWV、CIMT、ABI）的相关因素。
结果：
1.入组时患者资料对比显示，两组的糖尿病病程、性别、年龄、体重、BMI、HR、SBP、DBP、hsCRP、胰岛素每日总用量（TDD）、FBG、2hPG、HbA1c、FINS、TG、TC、LDL-C、HDL-C比较均无统计学意义（p>0.05）。
2.6个月后，达格列净组的体重、BMI、hsCRP、SBP、TDD均低于对照组，差异有统计学意义（p<0.05）;达格列净组的FBG、2hPG、HbA1c、TC、LDL-C较基线均有降低，差异具有统计学意义（p<0.05）。
3.两组患者治疗前后血管内皮功能指标的比较
⑴达格列净组与对照组FMD、NMD基线比较未见统计学差异（p>0.05）;
⑵6个月后，达格列净组FMD（6.55±2.63%）明显高于对照组（5.35±2.14%），差异有统计学意义（p<0.05）;但治疗后组间NMD未见统计学差异（p>0.05）;
⑶与观察前基线相比，达格列净组FMD（6.55±2.63%）明显高于基线水平（4.63±1.80%），差异有统计学意义（p<0.05）;NMD组内比较未见统计学差异（p>0.05）。
4.两组患者治疗前后动脉硬化指标的比较
⑴达格列净组与对照组CIMT、baPWV、ABI基线比较无统计学差异（p>0.05）;
⑵6个月后，达格列净组baPWV（1337±116cm/s）低于对照组（1408±137cm/s），差异具有统计学意义（p<0.001）;ABI、CIMT组间比较差异无统计学意义（p>0.05）;
⑶与观察前基线相比，达格列净组baPWV（1337±116cm/s）明显低于基线水平（1488±140cm/s），差异有统计学意义（p<0.001）;CIMT及ABI组内比较未见统计学差异（p>0.05）。
5.超重或肥胖T2DM患者血管内皮功能指标的单因素相关性分析
⑴FMD与达格列净使用呈正相关（r=0.216，p=0.001），与性别、BMI、HbAlc、SBP、hsCRP呈负相关（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）;
⑵NMD与BMI、SBP呈负相关（r=-0.295，p<0.05;r=-0.034，p<0.05）。
6.超重或肥胖T2DM患者动脉硬化指标的单因素相关性分析
⑴baPWV与性别、年龄、hsCRP呈正相关（r=0.012，p<0.05;r=0.025，p<0.05;r=0.164，p<0.05）;baPWV与达格列净呈负相关（r=-0.201，p<0.001）;
⑵ABI与LDL-C呈正相关（r=0.166，p<0.05）;
⑶CIMT与BMI、SBP呈正相关（r=0.235，p<0.001;r=0.232，p<0.05）。
7.超重或肥胖T2DM患者内皮功能及动脉硬化影响因素的多重线性回归分析
⑴达格列净使用是FMD的保护因素（β=0.032，p<0.05）;hsCRP是FMD的独立危险因素（β=-0.025，p<0.001），SBP是NMD的独立危险因素（β=-0.047，p<0.001）;
⑵达格列净使用是baPWV的保护因素（β=-0.227，p<0.001），hsCRP、BMI、SBP是baPWV的独立危险因素（β=0.084，p=0.032;β=0.066，p=0.029;β=0.039，p=0.017），hsCRP是ABI独立的危险因素（β=-0.026，p=0.014）。
结论：达格列净发挥降糖、降压、减重以及降脂基础作用，并对超重或肥胖T2DM患者内皮细胞功能及动脉硬化有一定的改善作用。炎性因子hsCRP是超重或肥胖T2DM患者内皮功能及动脉硬化的独立危险因素。
关键词：达格列净，超重，肥胖，T2DM，血管内皮，动脉硬化
Abstract
Objective
The aim of this study is to analyze the effects of dapagliflozin on vascular endothelial function and atherosclerotic indexes in overweight or obese type 2 diabetes 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 T2DM patients.
Methods
In this study, patients who met the diagnostic criteria of overweight or obesity and T2DM 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(baPWV), 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 T2DM endothelial function indexes(FMD, NMD) and atherosclerotic indexes(baPWV, CIMT, ABI) associated factors.
Results
1.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, 2hPG, HbA1c, 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, 2hPG, HbA1c, 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, baPWV and ABI between the dapagliflozin group and the control group at baseline(p>0.05);
(2)After 6 months, baPWV(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, baPWV 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 , HbAlc, 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)baPWV 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 baPWV 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 baPWV(β=-0.227, p<0.001), hsCRP, BMI and SBP were independent risk factors for baPWV(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).
Conclusion
Dapagliflozin 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 T2DM. The inflammatory factor hsCRP is an independent risk factor for endothelial function and atherosclerosis in patients with overweight or obese T2DM.
Keywords: dapagliflozin, overweight, obesity, type 2 diabetes mellitus, vascular endothelium, atherosclerosis |
| Other Abstract | Study on the effects of dapagliflozin on vascular endothelial function AND atherosclerosis in overweight or obese type 2 diabetic patients
Abstract
Objective
The aim of this study is to analyze the effects of dapagliflozin on vascular endothelial function and atherosclerotic indexes in overweight or obese type 2 diabetes 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 T2DM patients.
Methods
In this study, patients who met the diagnostic criteria of overweight or obesity and T2DM 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(baPWV), 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 T2DM endothelial function indexes(FMD, NMD) and atherosclerotic indexes(baPWV, CIMT, ABI) associated factors.
Results
1.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, 2hPG, HbA1c, 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, 2hPG, HbA1c, 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, baPWV and ABI between the dapagliflozin group and the control group at baseline(p>0.05);
(2)After 6 months, baPWV(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, baPWV 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 , HbAlc, 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)baPWV 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 baPWV 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 baPWV(β=-0.227, p<0.001), hsCRP, BMI and SBP were independent risk factors for baPWV(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).
Conclusion
Dapagliflozin 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 T2DM. The inflammatory factor hsCRP is an independent risk factor for endothelial function and atherosclerosis in patients with overweight or obese T2DM.
Keywords: dapagliflozin, overweight, obesity, type 2 diabetes mellitus, vascular endothelium, atherosclerosis |
| Pages | 47
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| URL | 查看原文
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| Language | 中文
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| Document Type | 学位论文
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| Identifier | https://ir.lzu.edu.cn/handle/262010/462601
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| Collection | 第一临床医学院
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| Affiliation | 第一临床医学院
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| First Author Affilication | First Clinical School
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Recommended Citation
GB/T 7714 |
李倩. 达格列净对超重或肥胖T2DM患者血管内皮功能和动脉硬化影响的研究[D]. 兰州. 兰州大学,2021.
|
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