| Background: In 2010, an estimated 285 million people worldwide had diabetes mellitus, 90% of whom had type 2 diabetes mellitus(T2DM). The number of people globally with diabetes mellitus is projected to rise to 439 million by 2030, which represents 7.7% of the total adult population of the world aged 20–79 years. The high glucose levels in T2 DM can damage blood vessels, nerves and organs. Even a mildly raised glucose level that doesn’t cause any symptoms can have long-term damaging effects. Some of the complications include: heart disease and stroke, nerve damage, diabetic retinopathy, foot problems, miscarriage and stillbirth, and diabetic nephropathy, If the small blood vessels of the kidney become blocked and leaky, the kidneys will work less efficiently. Traditionally, metabolic and hemodynamic factors are the major causes of renal lesions in patients with DM, considered as one nonimmune disease. However, serial studies have shown that inflammation plays a vital role in the process of DN. T cells were proposed to participate in the development and progression of DN. CD4+ T helper(Th) cells are believed to play central roles in modulating immune responses. A recent study has shown that not only Th1/Th2 imbalance but also Th17/Treg imbalance contributed to the pathogenesis of some autoimmune/inflammatory diseases and other metabolic disease like T2 DM. Moreover, obesity is one of the known risk factor in the progression of type 2 DM. And obesity is frequently associated with low-grade inflammation.Objective: The objective of this research was to explore whether Th17/Treg balance plays an important role in the progress of obese and DN in type 2 DM. And further link to the pro- and anti- inflammatory cytokines in the study participants.Study Design: 110 adult patients with type 2 diabetes mellitus(T2DM) were recruited from the diabetes mellitus. A urine albumin: creatinine ratio(UACR) greater than 30mg/g Cr as albuminuria is used to identify patients with diabetic nephropathy(DN). Another fifty apparently healthy, age and sex matched control subjects were recruited based on normal BMI, and additional 30 obese but non diabetic age and sex matched subjects were also included in this study. This study was cross-sectional and blinded. All participants were nonsmokers and BMI greater or equal than to 25 kg/m2. It wastes my time.is cut-off value coincided as obese individuals. Th17/Treg and level of IL-6, IL-10, IL-21, IL-23, TGF-β1in serum were measured in Healthy, Obese, DM, DM Obese, DN and DN Obese groups.Methods: Blood samples were collected from all the participants and using flow-cytometry was performed to analyze CD4+CD25+Fox P3+ Treg and CD4+ROR t+IL-17A+ Th17 cells. Serum is stored at-80°C and cytokines are analyzed by using ELISA. Values is mainly have expressed as the mean ± standard deviation(SD). Data was analyzed using statistical software(SPSS vs 23 Graph Pad Prism 6.1). For a comparison of the different subgroups of the T2 DM patients and the control subjects, the data were first analyzed by One-way analysis of variance(ANOVA). Comparison between the two groups was carried out with T test. Correlations between two variables were assessed with Spearman’s rank correlation coefficient test and regression tests. A p value <0.05 was considered to be statistically significant. The study was conducted after the approval by the ethics committee of Tianjin Medical University.Results: The results of this research showed that healthy, obese non-diabetic individuals, and T2 DM groups(Lean, Obese, DN, Obese DN) were comparable as regards the mean age and sex with no statistical significant difference. Compared to the healthy control lipid all profile there had statistical significant differences. Moreover, there were statically significant differences in WBC and RBC count among the groups. In which higher and lower mean value of WBC and RBC count in obese and in all DM groups respectively compared to healthy individuals. However, except for basophil no significant difference with other differential count. Analysis of serum cytokines in our samples show that: healthy mean IL-6 was higher than other group. However, except healthy vs DN obese individual’s, other groups have no statistical difference in IL-6. IL-10 was statistically significant lower in DN group than healthy and obese individuals. In other diabetic groups, the mean of IL-10 is lower than healthy group. But the decreased IL-10 is not statistically significant. The mean of IL-21 was elevated statistical significantly in DN and DN obese groups in comparison with healthy group. In addition, DN obese group had significant higher IL-21 than DM groups. There is an increase in the mean of IL21 in Obese, DM, DM obese groups than healthy group, but it is not statistically significant. Compared to the non-DM groups(healthy, Obese), the mean of IL-23 was raised in DM, DM obese, DN, and DN obese groups. However, the elevated IL-23 was only statistically significant in DN obese group. TGF-β1 was also statistically significant elevated in DN compared to non-DM groups(healthy, Obese). However, there was no significance between DN obese and healthy group. Obese, DM obese and DN obese groups had lower tendency of TGF-β1 compared to healthy, DM, and DN groups, respectively. But the decrease in TGF-β1 is not statically significant. Th17 cells rivaled that: there was a significant increase in the proportion of Th17 cells in CD4+ T cells in DM obese, DN, and DN obese in comparison to healthy group. In another hand the flow cytometric analysis of Treg cells rivaled that: there was a significant decrease in the proportion of Treg cells in CD4+ T cells in DM obese, DN, and DN obese in comparison to healthy group. Investigation revealed the proportions of Treg cells in CD4+ T cells was negatively related to UACR, while the proportions of Th17 cells in CD4+ T cells were positively related to UACR. Additionally, the proportions of CD4+ in total T cells were positively related to UACR. The correlation of Th17 cells with UACR was almost equally significant as the correlations of Treg with UACR.Conclusions: The decline number of Treg cells and the increased Th17 cells may play critical roles in modulating immunologic homeostasis microenvironment of diabetic nephropathy. And the anti- and pro-inflammatory cytokines may play a key role in the process. A significantly decreased Treg cells and elevated Th17 cells are positively associated with nephrotic affection. And both Treg cells and Th17 cells are equivalently important in the development and progression of type 2 diabetic nephropathy. |
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