| Background and purpose: Clinical diagnosis of type 2 diabetes (T2DM) patients which were autoimmune diabetes in part, autoantibodies appeared in serum, including glutamic acid decarboxylase antibody (GAD-Ab), islet cell antibody (ICA) and other autoantibodies. Such patients were referred to as latent autoimmune diabetes in adult (LADA). LADA was a subtype of type 1 diabetes (slow onset autoimmune type), as same as classical insulin dependent diabetes mellitus (T1DM) in the autoimmune pathogenesis. Compared with the 1-DM, immune damage suffered on the isletβ-cell function of LADA was slow [1]. The occurrence of LADA was associated with immune response, especially critical for regulatory T cells (CD4+CD25+Treg cells).Because of lacking of enough immune suppression of regulatory T cells, effector T lymphocyte were excessively activated , therefore autoimmune diabetes were induced. In more recent studies it has been confirmed that forkhead transcription factor Foxp3 is a critical regulator of CD4+CD25+Treg cells'development and function. Today, the generation, development, maturation and functional molecular mechanism of this cell type have been yet to be realized. Clarify these issues have been great significances in many ways, including for the treatment of autoimmune diseases, such as LADA, providing rationale for inducing regulatory T cells to achieve the transplantation tolerance and preventing tumor immunity from escaping.In this study, serum levels of common indexs ,such as fasting plasma glucose (FPG), two-hour postprandial glucose (2hPG), fasting insulin (FIns), two-hour postprandial insulin (2hIns), fasting C peptide (FC-P), two-hour postprandial C peptide (2hC-P) ,GAD-Ab and ICA were detected from LADA group, T2DM group, T1DM group and control group, to guide the clinical differential diagnosis of LADA and T2DM, and to assess insulin resistance andβ-cell function in LADA patients. Serum levels of cytokines IFN-γ, IL-4 and IL-10 in LADA patients indirectly reflected the amount and function of Th1/Th2 cells, evaluated cellular immune status of LADA. The amount of peripheral blood CD4+CD25+regulatory T cells (Treg) and the expression level of intracellular transcription factor Foxp3 were detected. CD4+CD25+regulatory T cells and expression features of Foxp3 mRNA in LADA were observed in vivo, to explore the relationship between CD4~+CD25~+regulatory T cells and the pathogenesis of LADA, and to provide new ideas and rationale for clinical application of immune agents in treating autoimmune diabetes.Method: 1. Conventional methods were used to detect index in serum, for example glucose oxidase test for FPG, 2hPG, radioimmunoassay for FIns, 2hIns, FC-P, 2hC-P, GAD-Ab,ELISA assay for ICA, which were collected from T1DM group , LADA group, T2DM group and normal control. 2. The changes of serum cytokines in peripheral blood of 4 groups (IFN-γ, IL-4, IL-10) were detected by ELISA. 3. The number of CD3, CD4, CD25 T lymphocyte subsets in peripheral blood of 4 groups was detected with flow cytometry. 4. The expression level of transcription factors of Foxp3 mRNA in peripheral blood mononuclear cells of 4 groups was detected with RT-PCR. Results: 1.Autoantibodies (GAD-Ab or and ICA) of LADA group and T1DM group were positive while those in T2DM group and normal control were negative. 2. Conventional laboratory parameters results showed: FPG from LADA group was lower than that of T1DM (P<0.05), no difference with T2DM group(P>0.05); 2h PG from LADA group was lower than that from T1DM group(P<0.05), higher than T2DM group(P<0.05); FC-P, 2hC-P, FIns and 2hIns from LADA group were lower than those from T2DM group(P<0.05), higher than T1DM group(P<0.05). 3. Cytokines results showed: the level of IFN-γfrom LADA group was lower than that from T1DM group(P<0.05), higher than the T2DM group(P<0.05); the level of IL-4 and IL-10 from LADA group were lower than those from T2DM group(P<0.05), higher than the T1DM group(P<0.05); the level of IFN-γ, IL-4, IL-10 from LADA group, T1DM group and T2DM group were higher than those from control group(P<0.05). 4. The number of T lymphocyte subsets measurement results showed: peripheral blood CD4+T cells of LADA group and T1DM group were significantly higher than those of T2DM group and normal control group(P<0.05). The number of.CD4+CD25+ T cells of LADA group was higher than that of T1DM group (P>0.05), significantly lower than T2DM group and normal control group (P<0.05). The number of.CD4+CD25+ T cells of T1DM group significantly was lower than that of T2DM group and normal control group (P<0.01); the number of.CD4+CD25+ T cells between T2DM group and control group was not statistically significant (P>0.05). 5. The results of the expression level of Foxp3 mRNA showed: the expression level of LADA group was significantly higher than that of T1DM group (P<0.05), significantly lower than that of T2DM group and normal control group (P<0.05); the expression level of T1DM group was significantly lower than that of T2DM group and control group (P<0.01); the expression level between T2DM group and control group had no significant statistical difference (P>0.05). Conclusion: 1.Existing islet cell specific autoantibodies are an important symbol of LADA patients,which distincting from T2DM. 2.Th2 type cytokines in LADA patients were significantly lower than those of normal control group,which may be one of the damage factors of isletβcell function. 3.The reduction of the amount and activity of CD4+CD25+regulatory T cells in LADA patients, maybe one of the pathogenesis of the major mechanisms. |
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