| BackgroundWith the global economic developing, the prevalence of diabetes increases rapidly. A survey of Shanghai Jiaotong University has increased our concern. Survey shows that China’s diabetes prevalence rate has increased to 11.6% in 2010, with the total number of diabetes reaching 92.4 million. It is possible to predict the medical burden to our health will face a lot of pressure in this regard. Moreover, in many countries of the world, especially the United States, more and more people are obese because of reduced physical activity and increasing age. Currently, despite advances in drug therapy for blood glucose control of type 2 diabetes, the control of diabetes and its complications are not ideal, less than 40%.Moreover, insulin and oral hypoglycemic drugs may cause weight gain and effect metabolic control. Also, both multi-drug combination therapy increased the financial burden of patients and increased organ damage. Type 2 diabetes, particularly in obese type 2 diabetic patients, becomes a challenging problemin the medical therapy management.Surgical treatment for type 2 diabetes in obesity, as a new diabetes therapy,had been written into guidelines by the American Diabetes Association in 2009. In recent years, the short-term efficacy of surgical treatment of obese patients with type 2 diabetes has been affirmedbymany clinicians. Giving a new look of treatment to people with type 2 diabetes, this could be a new way to cure diabetes. However, the mechanism of surgical treatment for obese type 2 diabetes remains unclear, which becomes a bottleneck restricting the further development and promotion of the surgery.Studies have shown that obesity is a chronic subclinical inflammation, and type 2 diabetes has immune cell disorders. Such as pro-inflammatory molecule TNF-a mediates insulin resistance. And insulin resistance will remit after bariatric surgery in obese patients with type 2 diabetes. The relationship among inflammation, insulin resistance and metabolic surgery has caused us concern.PurposeIn this study, specimens from those who accepted laparoscopic gastric bypass surgery will be tested by flow cytometry and immune cell binding activity detection technology. T/B lymphocyte subsets and the difference of CD4+T cell activity preoperative and postoperative would be analyzed in obese and type 2 diabetic population. And correlation between clinical index and significantT/B lymphocyte subsets would be also analyzed to explore its role in surgical treatment for obesity and type 2 diabetes.MethodFirst, difference of T/B lymphocyte subsets before and after surgery was compared by a retrospective analysis between control group of 12 cases of normal composition and 26 cases with laparoscopic gastric bypass surgery.26 patients who underwent laparoscopic gastric bypass surgery in January 2015-July 2015 in Guangzhou Military Command General Hospital Metabolic Surgery center were retrospectively analyzed,in which 10 cases of them are obese type 2 diabetes,8 of them are type 2 diabetes and 8 of them are obesity.12 cases data were selected as a control group in health physical examination department in Guangzhou General Hospital of Guangzhou Military Command.Control group members had no serious heart, liver, and kidney cancer and other diseases such as allergic,non-allergic diseases, obesity, type 2 diabetes, infection and other autoimmune diseases that may cause abnormal.All of them have not been taking corticosteroids and other immunosuppressant. T/B lymphocyte subsets were analyzed using flow cytometry by MILLIPORE (Guava easyCyteHT type) operation. Different sets of experimental data for multiple comparisons were analyzed by SPSS 20.0 statistical software ANOVA (one-way ANOVA) methods and the difference in the same group before and after surgery were compared using paired-t test.Second, correlation analysis between T/B lymphocyte subsets and nutrition indicators, glucose and lipid metabolism indicators, renal function indicators.T/B lymphocyte subsets indicators screened out in the first part of the study and preoperative clinical testing and evaluation indicators, including nutrition indicators (albumin, transferrin, prealbumin), glucose metabolism (fasting glucose,2-hour postprandial blood glucose, glycated hemoglobin, fasting insulin, postprandial insulin, fasting C-peptide,2-hour postprandial C-peptide), lipid metabolism (triglycerides, cholesterol, low density lipoprotein, high density lipoprotein, apolipoprotein A1, apolipoprotein B), renal function (blood urea nitrogen, creatinine, urinary albumin, creatinine clearance) were analyzed. ANOVA (one-way ANOVA) analysis were used to compare between groups.Correlation analysis was analyzed by Person correlation analysis and stepwise regression analysis with SPSS 20.0 statistical software.Third, the changing of CD4+T cell activity in patients underwent gastric bypass surgery.Blood samples before and after laparoscopic gastric bypass surgery were collected. A standard control group was selected according to the above method in the first part. CD4+T cell activity stimulated by PHA was detected by a microplate reader (Molecular Devices Spectra Max M3). Activity of CD4+T cells stimulated by PHA in 2h and 18h were compared by multiple independent samples nonparametric test using SPSS 20.0 statistical softwareResult(1) The distribution of B cells (CD 19+/45) and B cells absolute value (CD 19/ 45) have no difference in four groups(P>0.05). Helper T cells (CD4+/3) was significantly higher in diabetic and obese diabetic group than that in control and obesegroup. CD4+/CD8+ratio in diabetic and the obese diabetic group is also significantly higher than control group. CD4+/CD8+ratio in obese diabetic group is higher than the obese group(P<0.05). NK cells (CD 16+/56+/45), NK cells absolute value (CD16/56/45) in obese diabetic, diabetic and obese group were significantly lower than the control group(P<0.05).(2) T cells(CD3+) in obese diabetic group decreased after surgery (69.43+ 6.52 vs 66.89+7.74, t=2.282,P=0.048), but it was not obvious. The difference compared with the preoperative index in diabetic group was not statistically significant. The absolute value of suppressor T cells (CD8/3)(853.25+360.55 vs 718+303.06, t=2.49, P=0.042), NK cells absolute value (CD16/56/45) (391.5 +113.47 vs 332.38+97.58, t=2.911, P=0.023) in obese group declined compared with preoperative and the difference was statistically significant.(3) With age and sex controling, BMI, FPG, HbAlc, fasting insulin, postprandial 2h C peptide, high density lipoprotein, blood urea nitrogen in the obese diabetic, diabetic, obese pgroup are significantly different(P<0.05).(4) CD4+/CD8+ratio was significantly negatively correlated to micro- albuminuria(r=-0.857, P=0.006), and NK cells (CD16+/56+/45) was negatively correlated with creatinine (r=-0.843, P=0.009) in diabetic group. In obese diabetic groups, helper T cells (CD4+/3) was significantly negatively correlated to transferrin,2-hour postprandial insulin(r1=-0.772, P1=0.009; r2=-0.827, P2=0.003).CD4+/CD8+ratio was significantly positively correlated to 2h postprandial insulin(r=0.698, P=0.025), and was significantly negatively correlated to postprandial 2h C peptide, apolipoprotein B, creatinine clearance rate(r1=-0.810, P1=0.004; r2=-0.701, P2=0.024; r3=-0.761,P3=0.011). NK cells (CD16+/56+/45) and transferrin, creatinine was significant positive correlation(r1=0.889, P1=0.001; r2=0.693, P2=0.026). NK cells absolute value and 2h postprandial insulin, microalbuminuria were significantly positively correlated(r1=0.700, P1=0.024; r2=0.634, P2=0.049). CD4+/CD8+ratio and 2-hour postprandial blood glucose were negatively correlated(r=-0.731, P=0.039) and positively correlated between NK cells absolute value and triglycerides(r=0.823, P=0.012) in the obese group.(5) With the age and sexmatching, CD4+T cell activity stimulated by PHA was no statistically significant difference in 2h and 18h in the pre-operative, post-operative group compared with the control group (P>0.05). CD4+T cell activity PHA-stimulated of 18h in preoperative and control groups was significantly higher than the rate of increase of 2h (P<0.05). There was no significant change in the post-operative group at above two time points (P> 0.05).Conclusion(1)The immune system is activated and in a micro-inflammatory state in type 2 diabetes or obese people with diabetes.Immune system component such as peripheral blood T lymphocyte subsets changed in obesity and T2DM patients.(2)T lymphocyte subsets of patients is closely related to some indicators of nutrition, glucose and lipid metabolism, kidney function, indicating that blood glucose control and T lymphocyte subsets was relevant. It is essential to monitor the changes in immune system functionin order to effectively control blood glucose and provideimmunomodulatory treatment when it is necessary.(3)Immune system disorders in type 2 diabetes and obesity in patients mainly remain in the changing number of T/B lymphocyte subsets. CD4+T cell activity possible did not change significantly. |
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