Abnormal Proportions Of Immune Regulatory T Cells In Peripheral Blood Of Type 2 Diabetic Patients With Diabetic Nephropathy

Objective:The most paradigmatic example of diabetic complication is diabetic nephropathy,which is manifested as high urinary albumin excretion(UAE).Approximately one third of all diabetic patients are affected by DN,which produces significant social and economic burdens and constitutes the most frequent cause of end-stage renal disease(ESRD).Nowadays,there are convincing data that relate the diabetes inflammatory component with the development of renal disease.However,the exact pathogenic mechanisms of DN remain incompletely understood.Our study aim to evaluate the changes of various immune regulatory T cells in peripheral blood mononuclear cells(PBMCs)of Type 2 diabetic patients with diabetic nephropathy(DN).Methods:A total of 67 type 2 diabetic patients were divided into the Type 2 diabetes mellitus(T2DM)group(39 patients)and DN group(28 patients).Another 28 healthy subjects were enrolled as normal control(NC)group.The clinical characteristics(age,male/female,family history of diabetes,BMI,blood pressure,plasma lipid parameters)were collected.The proportions of regulatory T cells(Tregs),T helper 1(Thl)cells,Th2 cells in PBMCs were analyzed with flow cytometry.Results:Compared with NC group,HbA1c,FPG and TG increased in T2DM group and DN group(P<0.05).Compared with NC group and T2DM group,HbA1c,TG and Cr increased in DN group(P<0.05).In NC group,T2DM group and DN group,the proportions of Thl cells are17.43±5.15%,20.13±5.49%,27.30±8.37%,Th1/Th2 ratios are 13.77±5.4%,23.07±14.42%,36.44±38.87%,the proportions of Tregs are 2.33±1.04%,1.10±0.48%,0.83±0.42%.Compared with NC group and T2DM group,the proportions of Thl cells,Thl/Th2 ratios increased in DN group,However,the proportions of Tregs significantly decreased(P<0.05).Association analysis found that UAER was positively correlated with the proportions of Thl cells and Thl/Th2 ratios,and it was negatively correlated with the proportions of Tregs.According to multiple linear regression analysis,TG was independently associated with Thl cells,HbA1c and DBP were associated with Th2 cells,SBP and HbA1c were associated with Thl/Th2 ratios,SBP and TG were associated with Tregs.Conclusions:There is a disorder of the distribution of CD4+ T lymphocytes in DN patients,characterized by the reduction in the number of Tregs and an imbalance of Thl/Th2 cells,which may play important roles in the onset and progression of DN.Metabolic and hemodynamic abnormalities further increase the immune disorder in T2DM patients,promoted the development of DN.