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Study On The Early Endothelial Function In First-degree Relatives With Normal Glucose Tolerant Of Type2Diabetes

Posted on:2015-11-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:J M RenFull Text:PDF
GTID:1224330467961102Subject:Endocrine and metabolic diseases
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Objective:To investigate the inflammatory effect of TNF-a on MS-1. Methods: MS-1was stimulated with TNF-a (lOng/ml) for different time points (0h,4h,24h,48h), cell morphology, proliferation and cellular adhesion moleculars were examined by microscope, MTT assay and flow cytometry. Results:under TNF-a stimulation, morphology and proliferation of MS-1were impaired in time-dependent manner, and also induce the expression of CAMs in endothelial cells was obviously increased compared to control group (p<0.05or0.01). Conclusion:TNF-a induces inflammatory damages on MS-1. The big vascular complications are one of the main causes of death and cripple in type2diabetes mellitus patients. Compared with non-diabetic patients, cardiovascular disease increased2-4times in T2DM patients, and the seriousness of vascular impairment has been greatly increased. The big vascular complications tend to increase in the first ten years when has been diagnosis as T2DM, and40%-50%ones have atherosclerosis, and the first-degree relatives including normal glucose tolerance of which is a high-risk population of T2DM. Numerous reaserches have considered that there have been has vasculaerendothelial cell activation and dysfunction for FDRs, and these are one of the main reasons for IR. Therefore, the research of early vascular endothelial function in high-risk groups with T2DM is of great importannce.For this tissue we did the fallowing four researches. We selected90type2diabetes mellitus randomly as diabetes group.100their normolglycemic first-degree relatives as observation group.90healthy controls without diabetic family history matched for age, sex and body mass index as control group. Part One:Antioxidant ability in early endothelial function in first-degree relatives with normal glucose tolerant of Type2diabetes. Methods:Compared their changes of antioxidant ability: superoxide dismutase(SOD), nitric oxide(NO), total antioxidant status(T-AOS), sRAGE and free fatty acid(FFA), blood lipid, glucose, the capability of insulin cell. Results:When observation group compared with control group, NO, SOD and sRAGE had increasing tendency (P>0.05). T-AOS had no remarkable change. P30minPG、TG and Homa-IR are higher (P<0.05). P30minINS, Homa-IS is significantly lower (P<0.05). FPG, P2hPG, P2hINS and GHbAlc have no siganificant differernce (P>0.05). Conclusion:the antioxidant ability in diabetes is lowing, and has insulin resistance and P-cell dysfunction. Part two:Inflammation in early endothelial function in first-degree relatives with normal glucose tolerant of Type2diabetes. Methods:observed the BMI, WHR, FPG, CH, TG, GHbA1c, CRP, IL-23, TNF-a between observation and control groups. Calculate the HOMA-IR. Result:When observation group compared with control group CRP, IL-23are higher and have remarkable correlation with HOMA-IR (r=0.412,P=0.001), TNF-a (r=0.458,P=0.000). Conclusion:CRP and IL-23have been higer in first-degree relatives with normal glucose tolerant of Type2Diabetes and has remarkable correlation with HOMA-IR. They are important cell factors in insulin resistance and inflammation. Part three:Filament dissolves in early endothelial function in first-degree relatives with normal glucose tolerant of Type2diabetes. Methods: examined the blood plasma t-PA, PAI-1, Fbg, BMI, FINS, GHbAlc, CRP, the blood lipids and so on. Result:the t-PA content is drop and the Fbg, PAI-1content is elevation. Conclusion:T2DM exist coneal high the condition and the hemoglutination, the filament dissolved the function exceptionally participate in T2DM trunk oathological change’s occurrence. Part four:analysis the endothelial function in first-degree relatives with normal glucose tolerant of Type2diabetes with ultrasonic and the level of ADMA, ET-1, LEP in serum. Methods:assay the serum ADMA, ET-1and LEP. The vascular function and arteriosclerosis parameters FMD, Ep, β, AC were measured by ultrasonography. Resuts:compared with the control group, the serum ADMA, ET-1, LEP of observation group significantly increased. Ep, β significantly increased(P<0.01), FMD significantly reduced (P<0.05), AC had decreasing trend, but the difference has no statistically significance (P>0.05). IMT has no significantly change. Ep,β have positive and independent relation with serum ADMA, ET-1and LEP; while AC, FMD have negatively and independent relation with serum ADMA, ET-1and LEP (P<0.05). Conclusion:Endothelial dysfunction and the change of arteries function were existed in normal glucose tolerance in FDRs with T2DM. Carotid atherosclerosis parameters and FMD were independently associated with serum ADMA, ET-1and LEP levels. These three serum parameters may important predictators for early atherosclerosis.
Keywords/Search Tags:Tumor necrosis Factor-alpha, Islet Microvascular Endothelial CellsIslet functionType2diabetes, First-degree relatives, Endothelial dysfunction, Arteriosclerosis, Antioxidant ability, Cell factors, The hemoglutination, the filamentdissolve system
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