Effect of Dulaglutide on the number of endothelial progenitor cells in peripheral blood of patients with type 2 diabetes mellitus
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摘要: 目的 了解度拉糖肽对2型糖尿病(T2DM)患者外周血内皮祖细胞(EPCs)数量的影响及其相关因素。方法 选取60例口服二甲双胍1000 mg/d治疗的T2DM患者，随机分为二甲双胍增量组(MET组，30例，口服二甲双胍2000 mg/d)和二甲双胍联合度拉糖肽治疗组(MET-DUL组，30例，二甲双胍1000 mg/d联合度拉糖肽1.5 mg/周皮下注射)，持续治疗4周。采用流式细胞术检测治疗前后CD34、CD133、KDR均为阳性的EPCs数量。结果 经4周治疗后，MET组外周血EPCs数量改变无统计学意义(P>0.05)，而MET-DUL组中外周血EPCs数量[(45.8±11.6)/106cell∶(26.1±13.4)/106cell]，一氧化氮(NO)[(118.9±18.6)μmol/L∶(71.6±13.9)μmol/L]均高于治疗前(P< 0.05)，BMI[(26.3±2.6) kg/m2：(27.1±2.5) kg/m2]低于治疗前(P< 0.05)。MET-DUL组中ΔEPCs与ΔBMI、ΔFPG相关系数(r)为-0.296、-0.218(P< 0.05)，与ΔNO的r为0.389(P< 0.05)。结论 度拉糖肽可提高T2DM患者外周血EPCs数量。Abstract: Objective To understand the effect of dulaglutide on the number of endothelial progenitor cells(EPCs) in peripheral blood of patients with type 2 diabetes mellitus(T2DM) and its related factors.Methods A total of 60 T2DM patients treated with oral metformin 1000 mg/day were selected and randomly divided into metformin incremental group(MET group, 30 cases, oral metformin 2000 mg/day) and metformin combined with dulaglutide treatment group(MET-DUL Group, 30 cases, metformin 1000 mg/day combined with subcutaneous injection of dulaglutide 1.5 mg/week) for 4 weeks. Flow cytometry was used to detect the number of EPCs positive for CD34, CD133 and KDR before and after treatment.Results After 4 weeks of treatment, the number of peripheral blood EPCs in the MET group did not change significantly(P>0.05), while the number of peripheral blood EPCs in the MET-DUL group[(45.8±11.6)/106 cell vs (26.1±13.4)/106 cell], nitric oxide(NO) [(118.9±18.6) μmol/L vs (71.6±13.9) μmol/L]were higher than those before treatment(P< 0.05), BMI[(26.3±2.6) kg/m2: (27.1±2.5) kg/m2]was lower than that before treatment(P< 0.05). In the MET-DUL group, the correlation coefficients(r) of ΔEPCs with ΔBMI and ΔFPG were-0.296, -0.218, and therwith ΔNO was 0.389(P< 0.05).Conclusion Dulaglutide can increase the number of blood EPCs in T2DM patients.
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Key words:
- Dulaglutide /
- diabetes mellitus, type 2 /
- endothelial progenitor cell /
- nitric oxide
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图 1 两组治疗前后EPCs数量比较
Figure 1. Comparision of the number of endothelial progenitor cells(EPCs)between pre-treatment and post-treatment in two groups
表 1 两组间治疗前后一般资料及临床特征比较
Table 1. Comparision of general data and clinical characteristics between pre-treatment and post-treatment in two groups
例(%), X±S 变量 MET组 t/χ2 P MET-DUL组 t/χ2 P 0周(30例) 4周(30例) 0周(30例) 4周(30例) 男性 17(56.7) 17(56.7) 0.000 1.000 18(60.0) 17(58.6) 0.012 0.914 年龄/岁 43.5±4.4 43.5±4.4 0.000 1.000 42.9±5.3 42.8±5.4 0.015 0.893 病程/月 9.3±1.4 9.3±1.4 0.000 1.000 8.8±1.3 8.7±1.2 0.016 0.882 BMI/(kg·m-2) 26.8±2.7 26.7±2.9 0.083 0.935 27.1±2.5 26.3±2.6 2.563 0.028 SBP/mmHg 141±14 140±15 0.096 0.924 139±12 136±13 -0.167 0.238 DBP/mmHg 94±11 94±12 0.077 0.967 93±12 93±12 0.019 0842 FPG/(mmol·L-1) 7.4±1.1 7.0±1.2 2.400 0.030 7.5±0.9 6.9±1.0 2.773 0.022 HbA1c/% 7.2±0.2 - - - 7.1±0.3 - - - TG/(mmol·L-1) 2.2±0.8 2.0±0.9 0.993 0.347 2.3±0.9 1.9±1.0 1.104 0.215 TC/(mmol·L-1) 5.7±1.3 5.6±1.2 0.205 0.842 5.6±1.2 5.5±1.1 0.198 0.796 HDL-C/(mmol·L-1) 1.4±0.3 1.4±0.4 0.106 0.918 1.3±0.2 1.4±0.3 -0.153 0.278 LDL-C/(mmol·L-1) 3.5±0.5 3.5±0.4 0.113 0.853 3.4±0.3 3.2±0.4 0.764 0.426 NO/(μmol·L-1) 68.9±14.7 73.6±13.9 -0.154 0.265 71.6±13.9 118.9±18.6 -10.537 < 0.001 VEGF/(pmol·mL-1) 211.7±25.8 219.5±22.7 -0.113 0.312 208.3±26.7 222.7±27.1 -0.242 0.136 SDF-1α/(pmol·mL-1) 2056.1±512.3 2069.4±496.5 -0.203 0.194 1989.6±531.7 2067.5±515.3 -0.198 0.176 EPCs/106cell 27.2±12.3 28.9±13.4 -0.189 0.236 26.1±13.4 45.8±11.6 -8.563 < 0.001 
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表 2 两组治疗前后临床指标Δ值的比较
Table 2. Comparision of Δ value of clinical indices before and after treatment between two groups
X±S 变量 MET组(30例) MET-DUL组(29例) t P ΔBMI/(kg·m-2) -0.11±0.08 -0.82±0.13 10.346 < 0.001 ΔSBP/mmHg -1.08±0.11 -2.45±0.27 0.895 0.504 ΔDBP/mmHg 0.02±0.04 0.03±0.02 -0.107 0.343 ΔFPG/(mmol·L-1) -0.41±0.04 -0.52±0.09 1.276 0.152 ΔTG/(mmol·L-1) -0.22±0.07 -0.25±0.10 0.374 0.723 ΔTCH/(mmol·L-1) 0.09±0.05 0.08±0.04 0.186 0.836 ΔHDL-C/(mmol·L-1) 0.01±0.01 0.01±0.01 0.068 0.971 ΔLDL-C/(mmol·L-1) 0.01±0.01 0.09±0.05 -0.074 0.462 ΔNO/(μmol·L-1) 6.14±1.08 38.9±9.83 -13.875 < 0.001 ΔVEGF/(pmol·ml-1) 9.18±0.85 13.71±6.63 -1.187 0.185 ΔSDF-1α/(pmol·ml-1) 13.95±5.37 49.26±25.32 -1.837 0.092 ΔEPCs/ 10-6cell 2.12±0.97 19.97±5.86 -10.479 < 0.001
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表 3 MET组ΔEPCs与其他临床指标Δ值间的Pearson相关分析
Table 3. Pearson correlation analysis of ΔEPCs with Δ value of other clinical indices in MET group
变量 ΔEPCs r P ΔBMI -0.104 0.298 ΔSBP 0.061 0.657 ΔDBP 0.045 0.701 ΔFPG -0.165 0.102 ΔTG -0.098 0.321 ΔTCH 0.013 0.828 ΔHDL-C 0.084 0.593 ΔLDL-C 0.057 0.687 ΔNO 0.182 0.114 ΔVEGF 0.102 0.301 ΔSDF-1α 0.062 0.654
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表 4 MET-DUL组ΔEPCs与其他临床指标Δ值间的Pearson相关分析
Table 4. Pearson correlation analysis of ΔEPCs with Δ value of other clinical indices in MET-DUL group
变量 ΔEPCs r P ΔBMI -0.296 0.013 ΔSBP 0.054 0.703 ΔDBP 0.048 0.784 ΔFPG -0.218 0.042 ΔTG -0.189 0.088 ΔTCH 0.018 0.801 ΔHDL-C 0.075 0.605 ΔLDL-C -0.101 0.287 ΔNO 0.389 0.001 ΔVEGF 0.161 0.159 ΔSDF-1α 0.138 0.285
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表 5 MET-DUL组中ΔEPCs与其他临床指标Δ值的多元线性回归分析
Table 5. Multiple linear regressions analysis of ΔEPCs with Δ value of other clinical indices in MET-DUL group
变量 β SE t P 95%CI ΔBMI -0.217 0.097 -3.328 0.019 0.351~0.892 ΔNO 0.396 0.127 7.591 0.000 0.195~0.767
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