The Study About The Expression Of NF-kappaB In Subjects With Various Glucose Tolerance And Diabetics Of Oral Antidiabetic Drugs Failure With Intensive Therapy

Objective To investigate the relationships between various glucose tolerance states, such as type 2 diabetes(T2DM), impaired glucose regulation (IGR), normal glucose tolerance(NGT), and inflammatory by comparing the level of NF-κB in peripheral blood mononuclear cells in subjects, to further study the level of NF-κB in progress of T2DM.Methods The subjects were selected form medical examination center, clinic service, and inpatients of our hospitals from Dec.2007 to Jun. 2008. According to oral glucose tolerance test(OGTT) of fasting blood glucose and postchallenge 2 hour blood glucose, the subjects were divided into (1)Normal glucose tolerance(NGT)group, 20 subjects(male/famale 11/9),the mean age (53.26±8.71) years, FBG (4.86±0.45)mmol/L, P2hBG (5.07±0.37)mmol/L; (2)Group IGR, 5.6mmol/L≤FBG<7.0mmol/L or 7.8mmo/L≤P2hBG 7.0mmol or P2hBG>l1.1mmol/L, 20 subjects(male/famale 9/11), the mean age (51.68±12.56)years, FBG(9.69±4.19) mmol/L, P2hBG(21.27±4.89)mmol/L; (4)Diabetic group B (the course of diabetes≥5 years), FBG>7.0mmol or P2hBG> l1.1mmol/L, 20 subjects(male/famale 10/10), the mean age(57.36±12.85)years, FBG (10.63±3.29)mmol/L, P2hBG(22.15±4.78) mmol/L. All of the subjects were to fast after 10h of the previous night, to execute OGTT, to test FBG, P2hBG, fasting insulin, postchallenge 2 hour insulin, and to calculate the HOMA-IR, HOMA-β. HbA1c, TG and TC were also tested.The expressions of NF-κB in peripheral blood mononuclear cells were measured by using enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM).Results1. In condition of various glucose tolerance from NGT, IGR to T2DM, HOMA-βgradually decreased, but HOMA-IR continuously increased.2. Comparison of the change of NF-κB level among all groups: The expressions of NF-κB increased according to the order of group; Diabetic B group>diabetic A group> IGR group>NGT group(P<0.01).3. Correlation analysis Linear correlation analysis showed that the expression level of NF-κB detected by FCM had positive relationship with the expression level of NF-κB detected by ELISA in all the subjects; the expression level of NF-κB detected by ELISA was positively related to fasting blood glucose (FBG), postchallenge 2 hour blood glucose (P2hBG), HbA1c, triglycerides (TG) and HOMA-IR(r=0.716; r=0.506;r=0.854; r=0.283; r=0.367;P<0.01), but negatively related to HOMA-β(r=-0.292,P<0.05).4. Multi-variate stepwise regression analysis :The NF-κB(detected by ELISA) was regarded as dependent variable and others parameters as independent variable, multi-variate stepwise regression analysis showed that significant positive relationship was found among NF-κB, FBG and HbA1c(β=0.657,P<0.01;0.259,P<0.05).Conclusion There is low-degree of inflammation in pre-diabetic state (IGR). Inflammation may take an important part in developing type 2 diabetes mellitus and insulin resistance. Objective To investigate the anti-inflammatory effect of insulin by comparing the change of NF-κB expressions level on peripheral blood mononuclear cells in type 2 diabetics of oral antidiabetic drugs failure before and after insulin intensive therapy.Method The subjects who regularly attended our Diabetes Clinic Study from Dec.2007 to Jun. 2008 were selected from medical examination center and inpatients of our hospitals. Total 20 normal healthy subjects (control group) were recruited into the study, the subjects(male/famale 12/8) with the mean age (50.50±10.59) years. Type 2 diabetics of oral antidiabetic drugs failure, 20 subjects(male/famale 9/11) with the mean age (54.36±12.85) years, were recruited into group B. Fasting blood glucose, insulin, C-peptide and postprandial 2 hour blood glucose, insulin, C-peptide after 100g bread meal test were checked in the group B before insulin intensive therapy. The change of NF-κB expressions were measured by using enzyme-linked immunosorbent assay(ELISA) and flow cytometry (FCM). Group B were given intensive insulin therapy for two weeks which included Continuous Subcutaneous Insulin Infusion (CSII) or Multiple Daily Injections (MDI). After insulin intensive therapy,the parameter were rechecked, and calculated the HOMA-IR, HOMA-β.Results (1) Analysis of clinical characteristics: The gender,age,BMI, WHR,DBP and TC of group B well matched by comparing with group A, but the FBG, TG and SBP were notable higher than those in the group A. (2)The expressions of NF-κB level on peripheral blood mononuclear cells in type 2 diabetics of oral antidiabetic drugs failure were significantly higher than those in controls (P<0.01),(3)After insulin intensive therapy, the expressions of NF-κB level were obviously lower than those before insulin intensive therapy in the group B(P<0.01).(4)And Fasting blood glucose, postprandial 2 hour blood glucose ,HOMA-IR remarkably decreased further(P<0.01), however, postprandial 2 hour insulin, C-peptide and HOMA-βbecame notable higher by comparing with pre-treatment(P<0.05).(5) Correlation analysis of descended NF-κB: the level of descended NF-κB(detected by ELISA) didn't have relationship with descended FBG,P2hB and HOMA-IR after insulin intensive therapy(r=0.205,0.27,0.11, P﹥0.05).Conclusion (1)There are a low-degree of inflammation reaction in type 2 diabetics.(2)Insulin not only can reduce blood glucose,but also inhibite the inflammatory reaction, Intensive insulin therapy can decrease the level of NF-κB in peripheral blood mononuclear cell in type 2 diabetics of oral antidiabetic drugs failure.(3)Intensive insulin therapy can improve insulin resistance and the functions of secretion to isletsβcells in type 2 diabetics of oral antidiabetic drugs failure.