Endothelial Dysfunction And Early Atherosclerosis In First-degree Relatives With Normal Glucose Tolerant Of Type 2 Diabetes Mellitus

Genetic factors play an important role in the pathogenesis of type 2 diabetes (T2DM), and the first-degree relatives including normal glucose tolerance of which is a high-risk population of T2DM. The big vascular complications of T2DM are one of the main causes of death and cripple in type 2 diabetes mellitus patients. Compared with non-diabetic patients, cardiovascular disease increased 2-4 times in T2DM patients, and the seriousness of vascular impairment has been greatly increased. Therefore, the research and prevention of early atherosclerosis in high-risk groups with T2DM has become a current research hotspot.Objective:Through the research of serum (asymmetric dimethylarginine, ADMA) and endothelin-1(ET-1) levels and endothelial dependence brachial artery dilation (FMD) and carotid atherosclerosis parameters [including pressure strain elasticmodulus (Ep), stiffness parameter (β), arterial compliance (AC)] in first-degree relatives (FDRs) with normal glucose tolerant of T2DM, to explore the states of vascular endothelial function and early atherosclerosis in the FDRs with normal glucose tolerant of T2DM, investigate the relationship of them, and analyze the related factors by correlation analysis.Methods:52 T2DM pedigree were collected from October 2009 to June 2010 in Qilu Hospital of Shandong University, The first-degree relatives were made up with children, brothers and sisters,48 cases with normal glucose tolerant were selected for the observation group according to an oral glucose tolerance test (OGTT experiment), male in 23 cases, and female in 25 cases, average (38.92±12.09) years; 38 healthy person with no family history of diabetes and no history of abnormal glucose tolerance were selected as control group, male in 18 cases, and female in 22 cases, average (43.43±15.99) years. Normal glucose tolerance diagnosis used 1999 WHO diagnostic criteria:the criteria are fasting glucose (FBG)<6.1 mmol/L and 2 hours glucose after oral 75 grams glucose (P2hBG)<7.8 mmol/1. Exclusion criterion: hypertension, heart cerebrovascular disease, family type hyperlipidemia and connective tissue diseases were excluded; the other effects of sugar metabolism disorders were eliminated, such as hypercortisolism, pituitary growth cell tumor, pheochromocytomas; acute infection, chronic depleting diseases with cardiac insufficiency, severe liver and renal insufficiency were removed. Subjects were not taking vascular active substance and lipid-lowering medication. Age, sex, the histories of smoking and drinking, height, weight, blood pressure [systolic (SBP), diastolic blood pressure (DBP)], waistline (WC), hip circumference (HC) of all the subjects were recorded, and body mass index (BMI) and waist-hip ratio (WHR) were calculated separately. FBG, blood lipid, and P2hBG were observed by enzyme technique. Insulin (INS) was determined by chemoiluminesence immunoassay, while ELISA was applied to detect ADMA and ET-1. Insulin resistance(IR), isletβcell function index (IS) and islet cells sensitive indices(ISI) were calculated by homeostasis model assessment, and atherogenic index of plasma(AIP) was calculated by logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (log[TG/HDL-C]). FMD, Ep, (3, AC were measured by High-resolution ultrasonography.Results:1. Comparisons of clinical data and blood index Compared with control group, the serum ADMA, ET-1, TG, Ln(FINS) and Ln(HOMA-IR), Ln(HOMA-IS) and AIP of observation group significantly increased, but HDL and Ln(ISI) decreased obviously(P of all< 0.05). 2. Comparisons of ultrasonic results Compared with control, in the observation group, carotid Ep,βsignificantly increased(P<0.01), FMD significantly reduced (P <0.05), AC had decreasing trend, but the difference was not statistically significance (P> 0.05). The change of IMT was not significantly.3. Multivariate linear correlation analysis results among various factors The general correlation analysis (Bivaviate process) displayed:Ep, beta were positively correlated with serum ADMA, ET-1 and TG levels, Ln(HOMA-IR), AIP, P2hBG, SBP, but negatively correlated with FMD (P<0.05). Serum FMD was negatively correlated with ADMA, ET-1 and TG level, Ln (HOMA-IR), AIP, P2hBQ SBP (P< 0.05). Partial correlation analysis (extra transportation charges process) showed:TG level, Ln(HOMA-IR), AIP, P2hBG, SBP were calibrated, Ep, beta were all positively and independent related to serum ADMA and ET-1; AC, FMD was negatively and independent related to serum ADMA and ET-1 (P<0.05).4. Linear stepwise regression results With ADMA, ET-1 and TG levels, Ln (HOMA-IR), AIP, P2hBG, SBP as independent variables, and beta as dependent variable, beta was positively correlated Ln(HOMA-IR) and P2hBG(complex correlation coefficient R2 were 0.467 0.353, respectively, P<0.01); AC as dependent variable, AC was negatively correlated with Ln(HOMA-IR) and P2hBG(complex correlation coefficient R2 were -0.414 -0.331, respectively P<0.05); Ep as dependent variable, Ln(HOMA-IR) was independent risk factors with Ep (complex correlation coefficient R2 was -0.449, P<0.01).Results:1. Endothelial dysfunction and the change of arteries function.were existed in normal glucose tolerance in FDRs with T2DM2. Ep, beta were positively correlated with serum ADMA and ET-1, but negatively correlated with FMD (P<0.05), so the change of the arteries function was closely correlativity with endothelial dysfunction.3. FMD was independent negatively correlation with serum ADMA and ET-1 levels, serum ADMA and ET-1 levels may be the symbol factor of endothelial dysfunction disorder. 4. Carotid atherosclerosis parameters were independently associated with and serum ADMA and ET-1 levels, serum ADM A and ET-1 level may predict early atherosclerosis.