Relationship Between CD4~+T Cell Subsets And Type 2 Diabetes Mellitus And The Regulatory Effect Of TCM On CD4~+T Cell Subsets:A Systematic Review And Meta-analysis

ObjectiveThe purpose of this systematic review and meta-analysis is to explore the changes of peripheral blood T helper cell 17(Th17),regulatory T cell(Treg)and Th17/Treg ratio in patients with type 2 diabetes mellitus(T2DM)based on case-control studies;to evaluate the effect of traditional Chinese medicine on CD4~+T cells in T2DM patients based on clinical and animal randomized controlled Trials(RCT).MethodsWe searched CBMdisc,CNKI,Wanfang,VIP,Pub Med,the Cochrane Library,EMBASE and web of science.All case-control trials and RCTs published before January 2020 were screened.All meta-analyses were conducted with STATA 12.0software.The registration number of PROSPERO is CRD42020167482.Results24 case-control studies,4 animal RCTs and 6 clinical RCTs were included for this systermatic review and meta-analysis.The results showed that:1)compared with the controls,T2DM patients had significantly increased the percentage of peripheral Th17(SMD=3.33,95%CI(2.41,4.26),P<0.001),and the ratio of Th17/Treg(SMD=2.35,95%CI(1.21,3.49),P<0.001)in T2DM patients,and had significantly decreased the percentage of peripheral Treg(SMD=-1.47,95%CI(-1.92,-1.01),P<0.001).2)Traditional Chinese medicine compound treatment can significantly reduce the level of Th17 cells(SMD=-1.51,95%CI(-2.30,-0.71),P<0.001),and Th1cell level(SMD=-2.10,95%CI(-2.46,-1.75),P<0.001)and Th1/Th2 ratio(SMD=-2.68,95%CI(-3.97,-1.39),P<0.001)in T2DM patients,and can significantly increase Treg cell level(SMD=1.97,95%CI(0.03,3.91),P=0.046)and Th2 cell level(SMD=1.21,95%CI(0.90,1.52),P<0.001)in T2DM patients.Subgroup analysis showed that:the percentage of peripheral Th17 was significantly higher(P<0.001),and the percentage of peripheral Treg was significantly lower(P<0.001)in the T2DM patients both with renal complications and without complication,respectively.Besides,the percentage of peripheral Treg in patients with T2DM alone was significantly higher(P<0.001)and The percentage of peripheral Th17 was significantly lower(P<0.001)than patients with diabetic nephropathy(DN).Moreover,in patients with DN,the percentage of peripheral Treg in patients with microalbuminuria was significantly higher than that of patients with massive albuminuria(P<0.001),while the percentage of peripheral Th17 was significantly lower than that of patients with massive albuminuria(P<0.001).In addition,traditional Chinese medicine compound prescription regulates the use of CD4~+T immune cells in diabetic patients:in 10 studies,9 studies used Astragalus,5studies used yam,3 studies used dangshen,2 studies used Coptis,Atractylodes,Atractylodes macrocephala,and poria.Conclusions1)Compared with the healthy control group,the ratio of Th17 cells,Treg cells and Th17/Treg ratio in T2DM patients increased.2)Whether T2DM has the renal disease or not may affect the outcome indicators;the degree of CD4~+T immune cell disorder may be aggravated with the development of diabetes and its complications.3)Traditional Chinese medicine compound treatment can downregulate Th1,Th17 cell level,up-regulate Th2,Treg cell level and improve Th1/Th2 ratio in T2DM patients.4)Astragalus membranaceus is the most frequently used Chinese herb medicine to regular CD4~+T immune cells in diabetic patients,followed by yam,dangshen,rhizoma atractylodis,Atractylodes macrocephala Koidz,Poria cocos,and Coptis.