Changes Of Vascular Endothelial Diastolic Function In The Early Stage Of T2DM And The Relationship Of It And SF,ox-LDL,IR

Background and Objective:Vascular endothelial Diastolic dysfunction in atherosclerosis is the initiating link, butstudy results on vascular endothelial function are not consistent at present, because Detectionon vascular endothelial function in the past mainly based on two-dimensional ultrasound, thedynamic changes of vascular endothelial function can not be automatic and continuousrecorded,and Under echo -tracking (ET),we can avoid these problems. While the mechanismof vascular endothelial diastolic dysfunction in type 2 diabetes mellitus(T2DM)is unclear,in T2DM the early stages ,relationship of the vascular endothelial diastolic function andserum ferritin(SF),Oxidized low-density lipoprotein(ox-LDL),Insulin resistance(IR) isnot reported now. this study Select patients with abnormal glucose metabolism withoutmacrovascular complications as compared with normal people, to explore the mechanism ofvascular endothelial diastolic dsfunction .Materials and methods:We randomly collect type 2 diabetes mellitus patients (T2DM) 60 (male 43, female 17)without macrovascular complications in our hospital Wards and outpatient from December 2007to June 2008, Impaired Fasting glucose and / or Impaired glucose tolerance (IFG / IGT) patients25 (19 males and 6 females); age and sex matched healthy subjects (NC) 35 (male 22, female13).In three groups , proportion of postmenopausal and non-menopausal women in the numbermatch.Under e-Tracking conductions,we use high-resolution ultrasound to detect flow-mediatedendothelium-dependent vasodilation (FMD) and nitroglycerin-endothelium-independentvasodilation (NMD ) in brachial artery, and detect the consumed time (T1) that blood vesselsreach maximum diameter in systolic during flow-mediated dilation of blood vessels and the time(T2) during nitroglycerin-mediated dilation. ox-LDL was measured by Enzyme-linkedimmunosorbent assay (ELISA); SF was detected by chemilum- inescent immunoassay., insulinresistance (IR) was assessed by insulin homeostasis model assessment HOMA-IR. At the sametime ,another parameters such as lipid Prolife, hemoglobin, liver and renal function, uric acid, red blood cell count, Glycated hemoglobin, Intimal-medial wall thickness of common carotidartery (IMT) were measured .ResultResults:1.Changes of FMD, NMD, T1, T2 in the three groups:(1) FMD was progressively decreased from NC to IFG / IGT and T2DM (F = 155.45, P =0.000). FMD was (7.11±0.90)% in NC group, (5.08±0.87)% in IFG / IGT group, (4.11±0.70)% T2DM group. (2) in T2DM group NMD (13.24±2.4)%was significantly lower thanNC group (20.02±2.64)% and IFG / IGT group (18.60±1.8)% (F = 103.85, P = 0.000), inIFG / IGT group and NC group, Despite the downward trend, NMD was not significantdifference (P> 0.05). (3) T1 was (68.73±6.05) S in T2DM group significantly longer thanT1(57.51±6.21) S in NC group and T1 ( 61.76±5.23) S in IFG / IGT group. compared withNC group, T1 in IFG / IGT group was no significant statistical difference. While T2 in threegroups was the same chang tends as T1.2. Changes of SF, ox-LDL, HOMA-IR in the three groups.(1)SF gradually increasesfrom NC group to IFG / IGT group and T2DM group, SF was (151.29±68.91) ng / ml inT2DM group, (209.05±64.59) ng / ml in IFG / IGT group and (279.29±91.00) ng / ml inNC group, it was significant statistical difference ( F = 29.063, P = 0.000). (2) HOMA-IRgradually increase from NC group to IFG / IGT group and T2DM group, HOMA-IR was(1.09±0.32) in NC group, (2.07±0.27) in IFG / IGT group and (2.36±0.28) in T2DMgroup. it was significant statistical difference[( F = 29.063, P = 0.000)]. (3) from NC group toIFG / IGT group and T2DM group, ox-LDL gradually increase[(10.77±5.27) ug / dl in NCgroup, (17.18±5.53) ug / dl in IFG / IGT group and (24.23±6.80) ug / dl in T2DMgroup ],it was significant statistical difference (F = 54.260, P = 0.000).3. correlation analysis of FMD and SF, ox-LDL, HOMA-IR ,other factorsIn three groups ,FMD negatively correlated with SF, ox-LDL, HOMA-IR, FBG, HbA1c,TC, TG, LDL-C, apoB, Lpa and WHR , and positively correlated with HDL-C and apoA,butIn different group, the extent of impact of these indicators on FMD was difference.in T2DMgroup, the correlation coefficient of FMD and ox-LDL,SF was highest (R -0.638 , -0.504; P< 0.01). In addition to the above indicators associated with FMD, In T2DM group , FMD negatively correlated also with the course of the disease (R -0.496,P<0.01). In IFG/IGT group,the correlation coefficient of FMD and HOMA-IR,WHR was highest (R --0.588 ,-0.554;P <0.01); in NC group, the correlation coefficient of FMD and HDL-C,apoA was highest (R0.512 ,0.488;P<0.01).4. correlation analysis of NMD and SF, ox-LDL, HOMA-IR and other factorsIn the three groups, NMD negatively correlated with HOMA-IR, TC, apoB, HbA1c, T2,from NC to IFG / IGT group and T2DM group, With the aggravation of abnormal glucosemetabolism, correlation degree of NMD and these indicators progressively Increase.In thethree groups, correlation degree of NMD and these indicators in T2DM group was highest ,the correlation coefficients of NMD and HOMA-IR, TC, apoB, HbA1c and T2 in T2DMgroup were (-0.542, -0.431, -0.365, -0.359; P <0.01)and-0.342 (P <0.05), whereas NMD don,t significantly correlate with SF,ox-LDL and other indicators.5. Multivariate regression Backword analysis of FMD and the risk factors associatedThe three groups, as a whole,Multi-variable regression analysis with FMD level as adependent variable and the risk factors associated as the independent variables indicated thatFMD significately relate with ox-LDL(β=-0.336,P<0.01), HOMA-IR(β=-0.242,P<0.01),SF(β= -0.198,P < 0.01), TC(β= -0.175,P <0.01)and ApoB(β= -0.079,P <0.05)。6.Multivariate regression Backword analysis of NMD and the risk factors associatedThe three groups as a whole,Multi-variable regression analysis with FMD level as adependent variable and the risk factors associated as the independent variables indicated thatFMD significately relate with HOMA-IR(β=-0.410,P<0.01), ApoB(β= -0.308,P <0.01)and TC(β= -0.223,P <0.05)。ConclusiConclusion:1. In subclinical atherosclerosis stages of T2DM, not only do FMD decrease , but alsoNMD do, this suggest that vascular endothelial funtionin impair in the eary stages of T2DM,while the reaction of vascular smooth muscle to NO decreased. In stages of IFG and IGT,only FMD impaired, while NMD wasn,t abnormal. This Suggests that reaction of vascularsmooth muscle to NO was normal. 2. In stages of T2DM, Time that flow-mediated or nitroglycerin-mediated vascularendothelial maximum diastolic diameter consume significantly longer, which further suggestthat NMD of T2DM patients decreased, the reaction of vascular smooth muscle to NOdeclined.3. In the subclinical atherosclerosis stage of abnormal glucose metabolism ,SF, ox-LDLand IR were important risk factors . Iron overload, oxidative stress increased, increasedinsulin resistance may be involved in vascular endothelial function in early injury.4. At different stages of abnormal glucose metabolism , the major risk factors that affectvascular endothelial function vary. In stage of T2DM, oxLDLand SF impact mostsignificantly on FMD. In stage of IFG and IGT, IR and WHR impact most significantly onFMD ,In the normal group, HDL and apoA protect higher against FMD.5. In subclinical atherosclerosis stages of abnormal glucose metabolism ,IR is anImportant risk factor of NMD. It may start and participate injury of vascular smooth muscle .