Matrix Metalloproteinases 9 And Subclinical Atherosclerosis In Impaired Glucose Tolerance Patients

【Background】In recent years,the prevalence rate of type 2 diabetes has a increased dramatically trend in the worldwide.WHO forecast:Patients with type 2 diabetes worldwide will reach 239 million in 2010,which will exceed 300 million by the year 2025.In the global,the prevalence of IGT as diabetes had increased year by year trends.A great deal of information indicated:IGT is a various stages of cardiovascular risk factors as diabetes.How to detect the atherosclerosis in IGT population in early stage and interfere before causing serious consequences becomes a hot research.Some markers existed in serum could change in concentration in the early stage of atherosclerosis,provide the basis for the early diagnosis of IGT patients with atherosclerosis.MMP-9 is one of these markers in great attention.【Objective】To discussion serum levels of MMP-9 expression in different groups of glucose metabolism,research the prediction effect of Serum MMP-9 on IGT sub clinical atherosclerosis.【Method】Choose the health examination group(older than 45 years) in the Zhujiang Hospital Outpatient from May 1 to August 1 in 2007.According to ADA screening standards on fasting blood glucose,we carried on a 75 g glucose tolerance test on the people whose FPG≥5.6mmol/L(173 cases).Divide all the OGTT subject(173 cases) into NGT group(A group),IGT group(B group),T2DM group(C group) according to the 1999 WHO diagnostic criteria on type 2 diabetes and IFG,IGT.IFG group(10 cases) was not involved in this study as the small number of cases.Select 79 cases for Carotid Doppler ultrasound examination in NGT groups,IGT groups,T2DM groups randomly by using the random sample function in SPSS 11.5.According to the results of carotid ultrasound,divide them into AS group(AS group) and without AS group (NAS group).Another,according to the OGTT result,divide the 79 cases into Normal group(A1 group),IGT without AS group(B1 group),IGT with AS group(B2 group), T2DM without AS group(C1 group),T2DM with AS group(C1 group).As the small number of cases,NGT with AS group was not involved in this study.All subjects were collected venous blood after 12 hours on an empty stomach. Determined serum MMP-9 in ELISA method which kits provided by the United States Rapidbio company.Plasma glucose,serum total cholesterol,triglycerides, high-density lipoprotein,low-density lipoprotein was determined in automatic biochemical analyzer.We measured blood pressure,height,weight and abdomen subcutaneous fat thickness,calculated body mass index(BMI) and waist-hip ratio (WHR) in all subjects.【Result】1.The Basic conditions in the three groupsComparison of basic conditions in NGT,IGT,T2DM groups found:the age difference wasn't found in the three groups,which means comparable.BMI, WHR,abdominal subcutaneous fat thickness,systolic blood pressure,diastolic blood pressure were all significantly upward from NGT to IGT,T2DM groups.As follows:Age:NGT group 55(50.5～63) year,IGT group 62(53～70) year,T2DM group 61.5(54～67) year,no statistical difference was found among the three groups.BMI:The BMI in the IGT group(23.79±2.89) and T2DM group(25.384±3.52) were significantly higher than that NGT group(22.30±3.9(3)(P=0.000,F=8.184); WHR:The WHR in the IGT group(0.87±0.06) and T2DM group(0.90±0.09) were significantly higher than that NGT group(0.82±0.06)(P=0.000,F=16.703 );Abdominal subcutaneous fat thickness:The abdominal subcutaneous fat thickness in the IGT group(18.32±7.11)mm and T2DM group(19.28±7.74)mm were significantly higher than that NGT group(15.90±6.59) mm(P=0.002,F=6.362)Systolic blood pressure:The systolic blood pressure in the IGT group 140 (124～143) mmHg and T2DM group 140(125～150) were significantly higher than that NGT group 130(110～139) mmHg(P=0.002,χ~2=12.384);Diastolic blood pressure:The diastolic blood pressure in the IGT group 80 (70～90) mmHg and T2DM group 80(73.5～90) mmHg were significantly higher than that NGT group 70(70～85) mmHg(P=0.048,χ~2=6.089).2.The detection indicators in the three groups:Comparison of detection indicators in NGT,IGT,T2DM groups found:MMP-9, TG,LDL-C were all increased from NGT to IGT,T2DM significantly,But HDL-C decreased from NGT to IGT,T2DM significantly.AS follow:MMP-9:The MMP-9 in the IGT group 2.65(1.33～5.35 ) ng/ml and T2DM group 3.33(1.98～8.28) ng/ml were significantly higher than that NGT group 2.52 (2.23～4.07) ng/ml(P=0.000,χ~2=18.648);TG:The TG in the IGT group 1.27(0.89～1.75) mmol/L and T2DM group 1.75 (1.19～3.02) mmol/L were significantly higher than NGT group 0.87(0.63～1.16) mmol/L(P=0.000,F=25.763);TG in T2DM group was significantly higher than IGT group(P=0.000).CHOL:NGT group(15.90±6.59) mmol/L,IGT group(18.32±7.11) mmol/L,T2DM group(19.28±7.74) mmol/L,CHOL in T2DM group was significantly higher than NGT group(P=0.000,F=8.478).HDL-C:The HDL-C in the IGT group 1.13(0.99～1.28) mmol/L and T2DM group 1.13(1.03～1.44 ) mmol/L were significantly higher than that NGT group 1.52 (1.21～1.70) mmol/L(P=0.000,χ~2=22.138);LDL-C:The LDL-C in the IGT group 2.89(2.50～3.26) mmol/L and T2DM group 2.72(2.33～3.59) mmol/L were significantly higher than that NGT group 2.49 (2.22～2.68) mmol/L(P=0.000,F=9.173);3.Indicators between AS group and NAS group:Comparison of detection indicators between AS group and NAS group found: age,systolic blood pressure,WHR,abdominal subcutaneous fat thickness,MMP-9, CHOL,TG,LDL-C in AS group were significantly higher than that NAS group,but HDL-C was significantly lower than NAS group.AS follow:Age:NAS group(55.19±8.12)year,AS group(64.63±8.30)year,age in AS group was significantly higher than NAS group(P=0.000,t=-5.045);BMI:NAS group(24.00±4.16),AS group(24.35±2.93),BMI between the two groups was no significant difference;WHR:NAS group(0.85±0.05),AS group(0.89±0.09),WHR in AS group was significantly higher than NAS group(P=0.019,t=-2.335);Abdominal subcutaneous fat thickness:NAS group(24.96±9.99) mm,AS group (29.71±8.67) mm,abdominal subcutaneous fat thickness in AS group was significantly higher than NAS group(P=0.029,t=2.231);Systolic blood pressure:NAS group 130(110～140) mmHg,AS group 140 (130～150) mmHg compared,systolic blood pressure in AS group was significantly higher than that of NAS(P=0.004,Z=-2.877);Diastolic blood pressure:NAS group 80(70～85) mmHg,AS group 85(70～90) mmHg compared,diastolic blood pressure between the two groups was no significant difference;MMP-9:NAS group(2.89±1.58) ng/ml,AS group(8.05±3.93) ng/ml,MMP-9 in AS group was significantly higher than that of NAS(P=0.000,t=-7.884); TG:NAS group 1.27(0.75～1.74) mmol/L,AS group 1.46(1.05～2.86) mmol/L,TG in AS group was significantly higher than that of NAS(P=0.013,t=-2.540);CHOL:NAS group4.87±0.77mmol/L,AS group5.43±1.11mmol/L,CHOL in AS group was significantly higher than that of NAS(P=0.008,t=-2.748);HDL-C:NAS group1.28(1.09～1.43) mmol/L,AS group1.09(1.00～1.29) mmol/L,HDL-C in AS group was significantly lower than that of NAS(P=0.028, Z=-2.201);LDL-C:NAS group2.55(2.27～2.77)mmol/L,AS group3.15(2.42～3.65)mmol/L, LDL-C in AS group was significantly higher than that of NAS(P=0.001,t=-3.211).4.The detection indicators in the five subgroups:Comparison of detection indicators in normal group,IGT without AS group,IGT with AS group,T2DM with AS group,T2DM without AS group found:MMP-9,TG, CHOL,LDL-C in IGT with AS group and T2DM with AS group were all significantly higher than the normal group,but HDL-C was significantly lower than the normal group;The MMP-9 in IGT with AS group was significantly higher than the IGT without AS group;As the same,the MMP-9 in T2DM with AS group was significantly higher than the T2DM without AS group.AS follow:MMP-9:normal group(2.83±1.32) ng/ml,IGT without AS group(2.83±1.94) ng/ml,IGT with AS group(7.894±4.08) ng/ml,T2DM without AS group(3.094±1.07) ng/ml,T2DM with AS group(9.124±3.48) ng/ml;IGT with AS group,T2DM with AS group compared with the normal group,MMP-9(P=0.000,F=18.539) was significantly increased;IGT with AS group compared with IGT without AS group(P =0.003),T2DM with AS group compared with T2DM without AS group(P=0.000), MMP-9 increased significantly;TG:normal group 0.72(0.64～0.84) mmol/L,IGT without AS group 1.40 (0.84～1.74) mmol/L,IGT with AS group 1.27(1.03～1.76) mmol/L,T2DM without AS group 1.62(1.21～2.40) mmol/L,T2DM with AS group 2.46(1.46～3.38 ) mmol/L; IGT with AS group and T2DM with AS group compared with normal group, TGincreased significantly(P=0.000,χ~2=20.742);CHOL:normal group(4.76±0.44)mmol/L,IGT without AS group(4.83±0.56) mmol/L,IGT with AS group(5.48±0.96) mmol/L,T2DM without AS group (5.09±1.31)mmol/L,T2DM with AS group(5.64±1.20) mmol/L,no statistical difference was found among the five groups.HDL-C:normal group 1.38(1.26～1.59) mmol/L,IGT without AS group 1.26(1.11～1.41)mmol/L,IGT with AS group 1.13(1.04～1.26) mmol/L,T2DM without AS group 1.09(1.00～1.37)mmol/L,T2DM with AS group 1.09(0.99～1.29)mmol/L,IGT with AS group and T2DM with AS group compared with normal group,HDL-Cdecreased significantly(P=0.010,F=3.630);LDL-C:normal group 2.45(2.03～2.68)mmol/L,IGT without AS group 2.67 (2.42～2.87) mmol/L,IGT with AS group 3.15(2.96～3.53) mmol/L,T2DM without AS group 2.46(2.27～2.59) mmol/L,T2DM with AS group 3.53(2.42～4.09) mmol/L, IGT with AS group and T2DM with AS group compared with normal group, LDL-Cincreased significantly(P=0.008,χ~2=13.694);5.Step by step logistic regression analysis:In the IGT without AS group and IGT with AS group,take age,sex,WHR, abdominal subcutaneous fat thickness,systolic blood pressure,MMP-9,CHOL,TG, HDL-C,LDL-C as independent variable,take AS as dependent variable for step by step logistic regression(Forward LR method),MMP-9(P=0.008,OR=1.861)and age (P=0.021,OR=1.238) were selected into the equation:y=-16.023+0.621x1+0.213x2, which R~2 value was 0.716.【Conclusion】1.With lower glucose tolerance,atherosclerosis risk increased gradually.The IGT group might has more atherosclerosis risk than NGT group.2.Serum MMP-9 level in the IGT patient is significantly higher than NGT people. The diversity of MMP-9 in different glucose tolerance group and diversity of atherosclerosis mobility in different glucose tolerance population is consistent in the trend.3.Serum level of MMP-9 in IGT with AS patient is significantly higher than those IGT without AS.MMP-9 might has role in the in the early prediction of cardiovascular disease in the IGT patient.