Changes Of INKT Cell Frequencies And Subsets In Type 2 Diabetes Mellitus And The Effects Of DPP4 Inhibitors On Them

Objective:The specific pathogenesis of type 2 diabetes(T2DM)is not yet very clear."Inflammation theory" considers type 2 diabetes as a chronic low degree of inflammatory disease,with a constant natural killer T cell(iNKT)to participate in the disease.Glucagon like peptide(GLP-1)is a gut derived hormone that promotes insulin synthesis and secretion,and achieves hypoglycemic effect.Two peptidyl peptidase-4(DPP-4),also known as CD26,has serine protease activity,which can degrade GLP-1 and play an important role in the pathogenesis of diabetes.DPP4 inhibitors can play a hypoglycemic effect by inhibiting the activity of DPP-4 and reducing the degradation of GLP-1.The inhibition of the immune system by the application of DPP-4 inhibitors is not clear.In this study,we studied the changes in the frequency and subsets of iNKT cells in patients with type 2 diabetes and DPP4 inhibitors,and discussed the role of iNKT cells in the pathogenesis of type 2 diabetes and the effect of DPP4 inhibitors on iNKT cells.Methods:In this study,we selected 30 newly diagnosed type 2 diabetic patients(T2DM)from March 2014 to February 2018 in two Department of Endocrinology,No.1Hospital of Jilin University,17 cases of newly diagnosed type 2 diabetics with non DPP-4 inhibitors for 3 months(N-DPP4),and newly diagnosed type 2 diabetics with oral DPP-4 inhibitors for 3 months(DPP4)15 cases,and 10 healthy controls(HC),detected the frequency and subsets of iNKT cells in peripheral blood,and analyzed their relationship with clinical indicators.Results:1.The body mass index,blood sugar,glycated hemoglobin and abdominal circumference of the three groups were significantly higher than those in the healthy control group,and there were statistically significant differences(p<0.05),while the fasting C peptide was lower than the healthy control group,with a statistically significant difference(p<0.05).In addition,the fasting blood glucose and glycated hemoglobin in the DPP4 group and the non DPP4 group were significantly lower than those in the new type 2 diabetes group(p<0.05),and the level of C in the DPP4 group was significantly higher than that of the other 2 groups of diabetic patients.2.Compared with healthy controls,the frequency of TCRV alpha 24+iNKT cell(p=0.047)in peripheral blood of newly diagnosed type 2 diabetic patients was decreased,with statistical significance.3.Compared with the healthy control group,the CD4+TCR-V beta 11+iNKT cells(p=0.005),CD4+TCR-V alpha 24+iNKT cells(p=0.001)and CD4+TCR-V alpha 24-J alpha 18+iNKT cells(p=0.001)were higher in the newly diagnosed type 2diabetes group.=0.005)reduced.CD4-CD8-TCR-V alpha 24+iNKT cells in the DPP4 inhibitor group(p=0.038)and non DPP4 inhibitor group(p=0.040)were higher than those in the newly diagnosed type 2 diabetes group.4.The frequency of CD4+TCR-V alpha 24 iNKT cells in the newly diagnosed type 2 diabetes group was positively correlated with body mass index(p=0.008,r=0.474)and abdominal circumference(p=0.029,r=0.400),and the frequency of CD4-CD8-TCR-V alpha 24 iNKT was negatively correlated with body mass index(p=0.008,r=-0.478),abdominal circumference(p=0.001,r=-0.583).Conclusion:1.DPP4 inhibitor can improve pancreatic islet function while lowering blood sugar.2.In newly diagnosed type 2 diabetic patients,the frequency of TCRV alpha24+iNKT cells decreased,the frequency of CD4+iNKT cells increased,and the frequency of CD4-CD8-iNKT cells decreased.3.Of the newly diagnosed type 2 diabetic patients,the proportion of CD4+iNKT cells is positively correlated with body mass index and abdominal circumference,and the proportion of CD4-CD8-iNKT cells is negatively correlated with body mass index and abdominal circumference,suggesting that obesity and adipose tissue may participate in the early onset of type 2 diabetes by regulating the changes in iNKT cellsubsets.4.Hypoglycemic therapy has a certain regulatory effect on iNKT cell frequency and subgroup,which may not be related to the type of hypoglycemic drugs,and the short term application of DPP4 inhibitors does not affect the frequency and subgroup of iNKT cells.