The Changes Of Serum Levels Of IL-22 And Proportion Of T Cell Subsets In New Patients With Type 2 Diabetes Mellitus Complicated With Non-alcoholic Fatty Liver Disease

Objective: Type 2 diabetes mellitus(T2DM)is a common endocrine metabolic disease featured with abnormal increase in plasma glucose level and lipid metabolism disorder.Nonalcoholic fatty liver disease(NAFLD)is a set of clinicopathological features dominated by fatty deposition or degeneration of liver tissue irrelevant to the history of heavy drinking or other well-identified reasons.The incidence of NAFLD in T2 DM population is significantly higher than that in healthy population.Insulin resistance(IR)is regarded as the common pathophysiological basis of T2 DM and NAFLD.In recent years,a variety of studies have shown that the pathogenesis of T2 DM and NAFLD is closely related to the autoimmune reaction of the organism.To comparison the variation of Serum Interleukin-22(IL-22)level and the proportion of different CD4~+T cell subsets(Th1,Th2,Th17,Treg,Th22)in the new onset of T2 DM patients complicated with NAFLD.To investigate their relationship with IR and the damage of pancreatic beta cell Secretion function.To analysis the correlation of Serum IL-22 level and CD4~+T cell subsets with the new onset of T2 DM complicated with NAFLD,and the immune and inflammation mechanism in the pathogenesis of the disease.To provide the screening factors for the early diagnosis of the disease.Methods: Fifty-six new onset T2 DM patients were recruited.Based on whether complicated with NAFLD,the patients were divided into 2 groups:T2DM group,in which a total of 27 cases(13 male,14female),mean age was58.47+7.04Y;T2DM complicated with NAFLD group,in which a total of 29cases(14 male and 15 female),mean age was 60.04~+7.03 Y At meanwhile,29 cases who were for healthy examination(15 male and 14 female),whose mean age was 54.41+4.78 Y,were recruited as the control group.The basic data such as height,weight,history of present illness,past history and family medical history was collected.The fasting blood samples were collected and the serum samples were separated from patients and healthy control for laboratory testing.Triglyceride(TG),Cholesterol(TC),Low density Lipoprotein(LDL),High density Lipoprotein(HDL),Alanine Transferase(ALT),Aspartate Transferase(AST),Glutamyl Transferase(GGT),Alkaline Phosphatase(ALP),C reactive protein(CRP),Fasting blood Glucose(FPG),Fasting insulin(FINS)and Fasting C peptide were tested.The insulin resistance index(HOMA-IR)was calculated according to the FINS and FPG values for evaluating the level of IR.Dynamic insulin secretion index(MBCI)and insulin secretion index(HOMA-?)were calculated to evaluate insulin secretion function.Serum IL-22 levels were measured by enzyme-linked immunosorbent assay(ELISA).The percentage of CD4~+Tcell subsets including Th1,Th2,Th17,Treg and Th22 cells in peripheral blood of the 3 groups were detected by Flow cytometry.Ultrasound was used to examine the liver and the liver fat content(LFC)was calculated.Compared the differences of serum levels of IL-22 and CD4~+Tcell subsets percentage of the each group,analyzed their effects on the HOMA-IR,MBCI,HOMA-? and LFC,and explored whether they play roles in the pathogenesis of T2 DM complicated with NAFLD.Results:1 The levels of FPG,TG,TC,LDL,ALT,AST,FINS,Hb A1 c and HOMA-IR in T2 DM group were higher,respectively.The levels of HDL,HOMA-? and MBCI in T2 DM group were lower,respectively.The differences had statistically significant(P<0.05).Compared with the control group,the results in the T2 DM complicated with NAFLD group were same,and the differences had statistically significant(P<0.05).Compared with T2 DM group,the levels of TC,LDL,ALT,GGT,ALP,FINS,HOMA-IR,LFC and CRP were higher in the T2 DM complicated with NAFLD group,and the differences had statistically significant(P<0.05).2 Compared with the control group,the serum level of IL-22 was significantly higher in T2 DM complicated with NAFLD group.The difference was statistically significant(P<0.05).The proportion of the Th cell of CD4~+T cell subsets in peripheral blood,especially Th22 cells,increased in different degrees in the T2 DM group and T2 DM complicated with NAFLD group(P<0.05).The proportion of Th1 cells in T2 DM complicated with NAFLD group was significantly higher than that in T2 DM group and control group(P<0.05);The proportion of Th17 cells in T2 DM complicated with NAFLD group and T2 DM group was significantly higher than that in control group,the difference was statistically significant(P<0.05).The proportion of Treg cells in T2 DM complicated with NAFLD group was lower than that in control group(P<0.05),but had no significant difference in T2 DM group and T2 DM complicated with NAFLD group(P>0.05).3 Correlation analysis showed that there was a correlation between Th cell subsets of the different increased CD4~+T cells.Th22 was positively correlated with Th1 and Th17(r was 0.567 and 0.702,respectively.P<0.01);Th1 was positively correlated with Th17(r=0.405,P<0.01);The proportion of Th22 cells and the serum levels of IL-22 were positively correlated with HOMA-IR(r was 0.591 and 0.645,respectively.P<0.01),and were negatively correlated with HOMA-?(r was-0.69 and-0.68,respectively.P<0.01).Conclusion: The serum level of IL-22 was significantly increased in patients with new onset T2 DM.The serum levels of IL-22 and CD4~+cells were significantly up-regulated in T2 DM patients with NAFLD,the exception can be further aggravated.The proportion of Th22 cells and serum levels of IL-22 were positively correlated with HOMA-IR and negatively correlated with HOMA-?,which could partly interpret the role of immune and inflammation in the pathogenesis of T2 DM complicated with NAFLD.The proportion of Th22 cells and serum levels of IL-22 could possibly be used as early sensitive indexesfor the diagnosis of T2 DM complicated with NAFLD.