二甲双胍对2型糖尿病伴甲型流感患者外周血调节性T细胞/Th17细胞及相关细胞因子水平的影响

Effects of metformin on peripheral blood Treg/Th17 cells and related cytokines in patients with type 2 diabetes mellitus and influenza A

目的探究二甲双胍对2型糖尿病(T2DM)伴甲型流感患者外周血调节性T细胞(Treg)/Th17细胞及相关细胞因子水平的影响。方法前瞻性选择2021年4月至2022年4月浙江省荣军医院就诊的T2DM伴甲型流感患者108例,按照患者用药方式的不同分成观察组54例和对照组54例。观察组采用奥司他韦+二甲双胍治疗,对照组采用奥司他韦+格列齐特治疗。比较两组奥司他韦平均用药天数、平均用药总克数、血乳酸浓度及血气水平,比较两组治疗前、后的Th17、Treg细胞数及相关细胞因子水平。结果观察组奥司他韦用药天数、用药总克数及血乳酸浓度均高于对照组[(8.94±0.88)d比(7.23±0.79)d、(1.32±0.15)g比(1.08±0.11)g、(1.83±0.43)mmol/L比(1.61±0.32)mmol/L],差异有统计学意义(P<0.05);治疗后两组pH、动脉血氧分压、动脉血二氧化碳分压水平与治疗前比较差异无统计学意义(P>0.05);治疗后观察组Treg细胞数、白细胞介素-10、白细胞介素-4、CD_(3)^(+)、CD_(4)^(+)及CD_(4)^(+)/CD_(8)^(+)水平均低于对照组[(35.48±5.64)%比(42.53±6.17)%、(30.49±4.72)ng/L比(35.64±5.08)ng/L、(32.15±3.06)ng/L比(35.33±3.12)ng/L、(61.39±3.28)%比(66.27±3.05)%、(34.12±1.93)%比(36.59±2.61)%、1.26±0.34比1.52±0.41],差异有统计学意义(P<0.05);治疗后观察组的Th17细胞数、Th17/Treg、白细胞介素-17、γ-干扰素均高于对照组[(8.69±1.42)%比(7.94±2.03)%、0.24±0.06比0.19±0.05、(17.67±3.11)ng/L比(12.18±3.42)ng/L、(287.48±45.12)ng/L比(254.27±41.09)ng/L],差异有统计学意义(P<0.05);治疗期间观察组与对照组的不良反应发生率比较差异无统计学意义(P>0.05)。结论奥司他韦联合二甲双胍能够在一定程度上恢复T2DM伴甲型流感患者Th17/Treg细胞平衡,临床需注意监测乳酸水平。

Objective To explore the effects of metformin on levels of peripheral blood regulatory T cells(Treg)/Th17 cells and related cytokines in patients with type 2 diabetes mellitus(T2DM)and influenza A.Methods A total of 108 patients with T2DM and influenza A treated in Zhejiang Veteran Hospital were prospectively enrolled between April 2021 to April 2022.According to different medication methods,they were divided into observation group(54 cases,oseltamivir+metformin)and control group(54 cases,oseltamivir+gliclazide).The average usage time and dosage of oseltamivir,concentration of blood lactate and blood gas level,counts of Th17 and Treg cells,and levels of related cytokines in the two groups were compared before and after treatment.Results The average usage time and dosage of oseltamivir,and concentration of blood lactate were higher in observation group than control group:(8.94±0.88)d vs.(7.23±0.79)d,(1.32±0.15)g vs.(1.08±0.11)g,(1.83±0.43)mmol/L vs.(1.61±0.32)mmol/L,P<0.05.The differences in pH,partial pressure of arterial oxygen(PaO2)and partial pressure of arterial carbon dioxide(PaCO2)between the two groups had no statistically significant before and after treatment(P>0.05).After treatment,the differences in count of Treg cells,interleukin-10(IL-10),interleukin-4(IL-4),CD_(3)^(+),CD_(4)^(+)and CD_(4)^(+)/CD_(8)^(+)between the observation group and the control group were statistically significant:(35.48±5.64)%vs.(42.53±6.17)%,(30.49±4.72)ng/L vs.(35.64±5.08)ng/L,(32.15±3.06)ng/L vs.(35.33±3.12)ng/L,(61.39±3.28)%vs.(66.27±3.05)%,(34.12±1.93)%vs.(36.59±2.61)%,1.26±0.34 vs.1.52±0.41,P<0.05.After treatment,the count of Th17 cells,Th17/Treg,interleukin-17(IL-17)andγ-interferon(IFN-γ)in the observation group were higher than those in the control group:(8.69±1.42)%vs.(7.94±2.03)%,0.24±0.06 vs.0.19±0.05,(17.67±3.11)ng/L vs.(12.18±3.42)ng/L,(287.48±45.12)ng/L vs.(254.27±41.09)ng/L,P<0.05.During treatment,the difference in incidences of adverse reactions between the two groups had no statistically significant(P>0.05).Conclusions Oseltamivir combined with metformin can recover the balance of Th17/Treg cells in patients with T2DM and influenza A to a certain extent.Clinically,level of blood lactate should be monitored.