| IntroductionType 2 diabetes mellitus(T2DM) is increasingly prevalent worldwide. Impaired glucose regulation (IGR) is the early stage of T2DM. Development of atherosclerotic disease is the principal complication in T2DM, but clinical atherosclerotic disease can also precede development of diabetes. It has been demonstrated that endothelial dysfunction and imflammation may play a crucial role in the development and progression of atherosclerosis. To explore whether there were endothelial dysfunction and inflammation exist in subjects with various glucose tolerances, the concentration of serum soluble intercellular adhesion molecule - 1 ( SICAM - 1) , soluble vascular cell adhesion molecule - 1 (SVCAM -1) and high sensitivity C - reactive protein ( hs - CRP) were measured in subjects with nomal glucose torlerance(NGT) , IGR and T2DM.MaterialSamples1. Experiment group:75 subjects come from the medical examination center of The First Hospital Affiliated to China Medical University, divided into four groups according to oral glucose tolerance test(OGTT) , ( i )25 patients with impaired fasting glucose ( IFG);( ii ) 13 patients with impaired glucose tolerance (IGT);(iii)22patients with IFG and IGT(IGT/IFG);( iv)15 patients with newly diagnosed,complication - free type 2diabetes.2. Control group: 15 healthy volunteers with nomal glucose tolerance (NGT).Drugs and ReagentsHuman SIC AM - 1, SVCAM - 1 and hs - CRP kit, purchased from Dalian Fanbang chemical engineering technique exploitation company. 75 g standard glucose powd and distilled water, purchased from China Medical University.InstrumentBIO - RAD Model 550 microplate reader, Immulite 2000 Analyzer, constant temperature box ( BHW - 2 ) , automatic biochemical analyzer ( CX - 9 ) , Hitachi centrifuge instrument (himacCF7D2) , deep freeze vefrigerator.Method1. common clinical determination of subjects: age, sex, body height, weight, blood pressure, waist and hip circumference were measured, and to compute body mass index (BMI) and waist - to - hip ratio ( WHR ).2. OGTT and collection of specimen;After a 10 - hour overnight fast, blood were withdrawn to measure plasma glucose(FPG) , insulin, glycosylated haemoglobinAlc( HbAlc) , lipids, SICAM - 1, SVCAM - 1 and hs - CRP in the basal state, a 75g oral glucose tolerance test were preformed, at 2 hour of the OGTT, blood were withdrawn to mease plasma glucose(2hPG) and insulin and to compute HOMA insulin resistance index ( HOMA - IR) and HOMA insulin secretion index ( HOMA - ￡).3. determining of SICAM - 1 and SVCAM - 1;use the enzyme - linked im-munosorbent assay method.4. determining of hs -CRP: use the enzyme -linked immunosorbent assay method.5. Statistical analysis: Statistical analysis were done using SPSS11. 5 statistical software. ANOVA, LSD, Pearson correlation analysis and multivariate regression analysis were used.Results1. Comparision of clinical and biochemical characteristics in various groupsThere were no statistical differences among the five groups in age, sex, BMI, triglyceride(TG) , total cholesterol (TC) , low density lipoprotein cholesterol ( LDL - C) and high density lipoprotein cholesterol ( HDL - C). Compared with NGT group , the IGR and T2DM groups had significantly higher HOMA -IR. The IFG/IGT and T2DM groups had significantly higher WHR compared with NGT group.2. Measurement of SIC AM -1/SVC AM -1 and hs - CRP in various groups The IFG/IGT and T2DM groups had significantly higher serum levels of SI-CAM -1 and SVCAM - 1 compared with NGT group. The IFG, IFG/IGT and T2DM groups had significantly higher serum levels of hs - CRP compared with NGT group.3. Correlation analysisThe serum levels of SIC AM - 1 significantly correlated with age, FPG, 2hPG, HbAlcand HOMA - IR. The serum levels of SVCAM - 1 significantly correlated with FPG, 2hPG, HbAlcand HOMA - IR. The serum levels of hs -CRP significantly correlated with WHR, FPG, 2hPG, TG, LDL-C, HbAlcand HOMA - IR, inversely and significantly correlated with HDL - C and HOMA -(3. SIC AM - 1 significantly correlated with SVCAM - 1, hs - CRP significantly correlated with SVCAM - 1.4. Multivariate regression analysisTake BMI, WHR, SBP, DBP, FPG, 2hPG, TG, TC, LDL-C, HDL -C, HbAlc, HOMA - IR and HOMA - 3 as independent variable;SICAM - 1, SVCAM - 1 and hs - CRP as dependent variable. Doing multivariate regression analysis, affecting factors of SICAM - 1 were HbAlc and HOMA - IR;Affecting factors of SVCAM -1 were 2hPG;Affecting factors of hs - CRP were FPG, HOMA - IR, HOMA - p, 2hPG and WHR.DiscussionCellular adhesion molecules ( CAMs) are molecules expressed on the surface of a cell that mediate the adhesion of the cell to other cells or to the extracellular matrix. Intercellular adhesion molecule - 1 (ICAM - 1) and vascularcell adhesion molecule - 1 ( VCAM - 1) belong to the immunoglobulin superfam-ily. The adhesion of circulating leukocytes to the endothelial cells plays an important role in the initiation of atherosclerosis. Adhesion molecules, such as ICAM -1 and VCAM - 1, play key roles in this step. Soluble forms of some cellular adhesion molecules can be found in plasma;it has been suggested that elevated plasma levels of some CAMs may be an index of endothelial activation or even a molecular marker of early atherosclerosis. Type 2 diabetes mellitus is associated with an increased risk of premature atherosclerosis, it has also been reported that serum concentrations of soluble adhesion molecules are elevated in patients with T2DM. In the present study, we confirmed the presence of high serum concentrations of SICAM - 1 and SVCAM - 1 in T2DM patients. Moreover, we found that the presence of high serum concentrations of SICAM - 1 and SVCAM -1 in IGR patients. Our date demonstrate that endothelial function is already impaired in subjects with IGR. Further analysis indicated that both hyper-glycemia and insulin resistance were related to soluble adhesion molecules levels.Low - grade inflammation has been implicated in the development of type 2 diabetes. Inflammation markers such as C - reactive protein( CRP) are associated with insulin resistance and type 2 diabetes. CRP levels might predict the development of T2DM. In our study, we found that the presence of high serum concentrations of hs - CRP in T2DM group compared with NGT group. Moreover , we found that the presence of high serum concentrations of hs - CRP in IGR patients. Our date demonstrate that imflammation is already exist in subjects with IGR. Further analysis indicated that hyperglycemia, dislipidemia, abdomen - shape obesity, insulin resistance and insulin secretion dysfunction were related to hs - CRP levels.The marker of endothelial dysfunction - SVCAM - 1 correlated with the marker of imflammation - hs - CRP, and both of the two markers are related to hyperglycemia and insulin resistance. These results suggest that inflammation is closely associated with endothelial dysfunction. Endothelial dysfunction occurs in parallel with the development of chronic low - grade inflammation. We demonstrated that not only T2DM patients exist endothelial dysfunction and inflam-mation, but also in subjects with IGR. Endothelial dysfunction and inflammation might participate in the occurance and development of T2DM and its vascular complications.Conclusion1. Compared with NGT group, the IGR and T2DM groups had significantly higher serum levels of SICAM - 1 and SVCAM - 1, especially in IFG/IGT group. SICAM - 1 and SICAM - 1 levels are related to hyperglycemia and insulin resistance.2. Compared with NGT group, the IGR and T2DM groups had significantly higher serum levels of hs - CRP, especially in IFG and IFG/IGT group, hs -CRP levels may be related to hyperglycemia, dislipidemia, abdomen - shape o-besity, insulin resistance and insulin secretion dysfunction.3. The marker of endothelial dysfunction — SVCAM - 1 correlated with the marker of imflammation - hs - CRP, and both the two markers are related to hyperglycemia and insulin resistance. Endothelial dysfunction and inflammation might participate in the occurance and development of T2DM and its vascular complication.
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