2型糖尿病患者血管舒张功能和一氧化氮释放变化及与动脉硬化的关系

目的　探讨 2型糖尿病患者血管舒张功能和一氧化氮释放与糖尿病血管病变的关系。方法　选择 2 0名正常人 (对照组 )和 62例 2型糖尿病患者 (糖尿病组 ) ,并根据患者是否合并冠心病进行分组分析。采用高频超声方法测定反应性充血试验和口服硝酸甘油前后的肱动脉内径变化 ,以反映血管内皮依赖性和非内皮依赖性舒张功能 ,以及静脉闭塞试验测定一氧化氮储备释放 ,同时利用超声方法检测颈总动脉内膜厚度。结果　与对照组比较 ,糖尿病组的非内皮依赖性血管舒张功能无显著变化 (P >0 .0 5 ) ,而内皮依赖性血管舒张功能和内皮一氧化氮释放明显低下 (P<0 .0 5～ 0 .0 1) ,颈总动脉内膜厚度明显增厚 (P <0 .0 1)。糖尿病合并冠心病患者血管内皮依赖性和非内皮依赖性舒张功能均较非合并冠心病患者明显低下。结论　高频超声检测方法能够较好地判断糖尿病患者血管舒张功能。糖尿病患者存在明显的动脉硬化和因一氧化氮释放减少而出现的内皮依赖性舒张功能障碍 ,此与糖尿病性血管病变密切相关     

老年高血压患者的血管内皮功能变化及颈动脉内膜中层厚度改变的意义

目的：研究老年高血压患者血管内皮功能及颈动脉内膜中层厚度改变情况及其意义。方法：测定43例高血压患者血液中血管内皮功能受损行异性标志物NO、ET并采用高分辨率超声技术检测休息时、反应性充血后的肱动脉内径变化及颈动脉内膜中层厚度及斑块。同时与20例正常者进行对比。结果：老年高血压组肱动脉血流介导性舒张功能明显减弱，NO明显低于对照组，NT水平明显高于对照组。老年高血压Ⅱ期及Ⅲ期颈动内膜中层厚度及斑块发生率较对照组明显增高（P＜0．05），且随斑块严重程度的增加，内膜中层厚度呈增厚趋势。结论：颈动脉内膜中层厚度及内皮依赖性舒张功能障碍是老年高血压患者动脉粥样硬化的早期表现。     

急性高血糖对肱动脉内皮依赖性血管舒张功能影响的研究

目的 探讨葡萄糖负荷试验所致急性高血糖对血管内皮功能的影响。方法 选择正常健康人（NC）、糖耐量减低（IGT）患者和2型糖尿病（T2DM）患者各10例。所有对象均做OGTT，分别于0、60、120min采用高分辨血管外超声检测肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油（GNT）介导的内皮非依赖性血管舒张功能。结果 IGT组和T2DM组0、60、120min的内皮依赖性血管舒张功能均明显低于NC组（P〈0．05）。与0min相比，IGT组和T2DM组60min内皮依赖性血管舒张功能明显降低，120min又回升，明显高于60min者（P〈0．05）。IGT组和T2DM组在基础状态下，LDL-C、Lp（a）、FPG、HbA-C与内皮依赖性血管舒张功能呈负相关（P〈0．01）。在OGTT中，这两组血糖与内皮依赖性血管舒张功能呈负相关（P〈0．001）。结论 高血糖快速抑制内皮依赖性血管舒张功能。提示餐后高血糖在糖尿病血管并发症的发生与发展中起重要作用。     

X综合征患者血管内分泌功能和内皮依赖性舒张功能障碍的研究

目的　研究内皮依赖性舒张功能障碍在X综合征患者发病中的意义。方法　对 18例X综合征患者和 2 0例正常对照者 ,采用高分辨多普勒超声仪测定肱动脉基础、反应性充血和舌下含服硝酸甘油后血管舒张末期内径变化 ,并测定血浆内皮素 (ET)、一氧化氮 (NO)含量。结果　 (1)X综合征患者肱动脉血流介导的血管扩张较对照组明显减弱 ,含服硝酸甘油后血管明显扩张 ,但两组无显著差异 ;(2 )X综合征组较对照组ET水平显著升高 ,NO水平显著降低 ;(3)肱动脉血流介导的血管扩张与血浆ET水平呈显著负相关 ,与NO水平呈显著正相关。结论　X综合征患者存在血管内分泌功能紊乱、内皮依赖性舒张功能障碍 ,后者与内皮源性松弛因子减少有关。     

X综合征患者血管内分泌功能和内皮依赖性舒张功能障碍的研究

的 :研究内皮依赖性舒张功能障碍在X综合征患者发病中的意义。方法 :对 18例X综合征患者和 2 0例正常对照者 ,采用高分辨多普勒超声测定肱动脉基础、反应性充血和舌下含服硝酸甘油后血管舒张末期内径变化。并测定血浆内皮素 (ET)、一氧化氮 (NO)含量。结果 :1 X综合征患者肱动脉血流介导的血管扩张较对照组明显减弱 ,含服硝酸甘油后血管明显扩张 ,但 2组无显著差异。2 X综合征组较对照组ET水平显著升高 ,NO水平显著降低。 3 肱动脉血流介导的血管扩张与血浆ET水平呈显著负相关 ,与NO水平呈显著正相关。结论 :X综合征患者存在血管内分泌功能紊乱、内皮依赖性舒张功能障碍 ,后者与内皮源性松弛因子减少有关。     

血管内皮功能与血糖、胰岛素水平及心血管危险因素的相关性

目的 研究超重肥胖者血管内皮功能与血糖、胰岛素水平及心血管病危险因素的关系。方法 367例超重肥胖者被分成2型糖尿病组、糖耐量减低组、空腹血糖受损组、正常糖耐量组及单纯超重肥胖组，并与66例正常体重者对照。测定血管内皮依赖性舒张功能(血流介导)和内皮非依赖性舒张功能(硝酸甘油介导)，并测定体脂、血压、血糖、血脂和胰岛素抵抗指数(HOMA-IR)。结果 超重肥胖者的内皮依赖性舒张功能显著降低，合并代谢异常者降低更显著。血管内皮依赖性舒张功能与腰臀比、收缩压、HOMA-IR呈显著负相关。结论 超重肥胖者血管内皮功能受损，腰臀比、收缩压及HOMA—IR是影响内皮功能的主要因素。     

冠心病合并2型糖尿病患者的血清AGEs与内皮依赖性血管舒张功能关系探讨

目的　探讨冠心病合并 2型糖尿病 (2 - DM)患者内皮依赖性血管舒张功能与血清糖基化终产物(AGEs)水平变化及二者的关系。方法　选择 6 0例冠心病合并 2 - DM患者为治疗组 ,在冠心病综合治疗的基础上给予胰岛素或其他降糖药物控制血糖 ;另选 6 0例查体健康者为对照组。检测两组血清 AGEs、NO水平 ,采用 Jud-kins法进行选择性冠状动脉造影 ,高分辨超声技术检测肱动脉的血管舒张功能。结果　治疗组治疗前后血清AGEs、NO水平及内皮依赖性血管舒张功能均与对照组有明显差异 (P <0 .0 5 ,<0 .0 1) ,且治疗组治疗前后上述指标亦均有明显差异 (P <0 .0 1)。内皮依赖性血管舒张功能减弱程度与血清 AGEs水平呈负相关 (r =- 0 .39,P <0 .0 1) ,血清 NO水平与血清 AGEs水平呈负相关 (r=- 0 .31,P <0 .0 1)。结论　冠心病合并 2 - DM患者内皮依赖性血管舒张功能明显减弱 ,血清 AGEs水平明显升高 ,可能是 AGEs削弱了其内皮依赖性血管舒张功能。长期良好的血糖控制可降低冠心病合并 2 - DM患者血清 AGEs水平 ,增加血液中 NO水平 ,改善其内皮依赖性血管舒张功能     

2型糖尿病病人血管内皮依赖性舒张功能的改变

目的　了解 2型糖尿病病人血管内皮依赖性舒张功能的改变。方法　分别选取对照组、2型糖尿病组及 2型糖尿病合并血脂异常组 ,采用高分辨血管外超声法检测其肱动脉血流介导的内皮依赖性舒张功能和硝酸甘油介导的内皮非依赖性舒张功能。同时测定血脂水平。结果　 12型糖尿病组和 2型糖尿病合并血脂异常组内皮依赖性舒张功能较对照组均明显降低 ( P <0 .0 5) ;2型糖尿病合并血脂异常组较 2型糖尿病组有减退 ,但无显著差异 ( P>0 .0 5)。 2 2型糖尿病合并血脂异常组非内皮依赖性舒张功能较 2型糖尿病组及对照组减退 ,差异显著 ( P<0 .0 5) ;2型糖尿病组与对照组无显著性差异 ( P>0 .0 5)。结论　 2型糖尿病对血管内皮功能有影响 ,且影响因素是多方面的 ,既有糖代谢紊乱因素 ,又有脂代谢紊乱因素     

早期2型糖尿病患者内皮依赖性血管舒张功能改变的研究

目的　探讨早期 2型糖尿病患者内皮功能的变化。方法　选择 5 0例无血管并发症的 2型糖尿病患者 ,和 2 5例年龄、性别匹配的健康个体。采用高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油 (GNT)介导的内皮非依赖性血管舒张功能。结果　2型糖尿病组血流介导的血管舒张功能为 3 .62 % ,明显低于对照组的 4.68% (P <0 .0 5 )。基础血管内径、基础血流、GNT介导的血管舒张功能在 2组间无明显差异 (P >0 .0 5 )。结论　早期 2型糖尿病患者内皮依赖性血管舒张功能降低。     

2型糖尿病早期内皮依赖性血管舒张功能的临床研究

目的探讨2型糖尿病（T2DM）早期患者血管内皮功能的变化及其临床意义。方法选择44例新诊断无并发症的T2DM早期患者和40名年龄、性别等匹配的正常对照者。采集空腹静脉血测定FPG、Fins、HbA,c、TC、TG、HDL—C、LDL-C、UA、NO、内皮素1（ET～1）等,并行75g葡萄糖耐量试验测定2hPG。采用高分辨率血管外彩超测定肱动脉、颈动脉的血管内径及颈动脉内膜中层厚度（IMT）,以反应性充血前后血管内径变化百分比反映血管舒张功能。对IMT与各项指标的变化进行相关性分析。结果T2DM组与对照组之间FPG、Fins、2hPG、HbA1C、TG、TC、HDL—C、LDL-C、H（）MAIR、NO、ET-1差异均有统计学意义（P〈0．05或P〈0．01）,而性别、年龄、BMI、收缩压、舒张压、UA差异无统计学意义（P〉0．05）。T2DM组基础血管内径、血流介导的内皮依赖性舒张功能和硝酸甘油介导的非内皮依赖性舒张功能与对照组之间差异有统计学意义（P〈0．01）。基础血流在两组问差异无统计学意义（P〉0．05）。不同部位IMT在不同人群中的密切相关因素是不同的。结论T2DM早期患者就有血管内皮功能损伤,不仅存在内皮依赖性血管舒张功能障碍,而且存在非内皮依赖性血管舒张功能障碍。     

Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus

OBJECTIVES: The objective of this study was to evaluate endothelium-dependent vasodilation and carotid intimal-medial thickness (IMT) in children with insulin-dependent diabetes mellitus. BACKGROUND: Diabetes mellitus is an established risk factor for atherosclerosis. Vascular complications of diabetes are not clinically evident in diabetic children. However, preclinical atherosclerosis is more common in young subjects exposed to cardiovascular risk factors. Endothelial function and carotid IMT, known to be abnormal in preclinical atherosclerosis, have not been studied concurrently in a pediatric population exposed to a risk factor for atherosclerosis. METHODS: We studied 31 diabetic teenagers (age 15.0 +/- 2.4 years; duration of diabetes 6.8 +/- 3.9 years) and 35 age-matched healthy children (age 15.7 +/- 2.7 years). Using high-resolution vascular ultrasound, we compared carotid IMT and brachial artery responses to reactive hyperemia (endothelium-dependent vasodilation) and to sublingual nitroglycerin (endothelium-independent vasodilation). RESULTS: There was no difference in baseline brachial artery diameter between the two groups. Endothelium-dependent vasodilation was significantly lower in diabetic children compared with healthy children (4.2 +/- 3.8% vs. 8.2 +/- 4.2%, p < 0.001). There was no difference in endothelium-independent vasodilation (17 +/- 6% vs. 18 +/- 6%, p = NS) or mean carotid IMT between the groups (0.33 +/- 0.05 vs. 0.32 +/- 0.08 mm, p = NS). Endothelium-dependent brachial vasodilation correlated with blood glucose levels (r = 0.58, p = 0.001) and was weakly and inversely related to the duration of diabetes (r = -0.4, p = 0.02), total cholesterol, and low-density lipoprotein cholesterol levels. CONCLUSIONS: Endothelial function is impaired in children with diabetes mellitus within the first decade of its onset and precedes an increase in carotid IMT. The relative timing of these events is important in the evaluation of strategies to prevent progression of atherosclerosis and other vascular complications in this patient population.     

Association between insulin resistance and endothelial dysfunction in type 2 diabetes and the effects of pioglitazone

Endothelial dysfunction is regarded as an early stage of atherosclerosis, and plays a role in the development of atherosclerotic diseases. Insulin resistance is related to the atherosclerotic process. In this study, we examined the association between endothelial function and insulin resistance in 48 subjects with type 2 diabetes. In addition, the effects of pioglitazone treatment on endothelial function and insulin resistance were investigated in a subgroup of subjects. Endothelial function of the brachial artery was non-invasively assessed using ultrasound technique. We measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). Insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. High SSPG levels indicate insulin resistance. There was a significant inverse correlation (r=-0.462, p<0.001) between SSPG and FMD. Systolic blood pressure was inversely correlated with FMD (r=-0.360, p<0.013). By multiple regression analysis, insulin resistance was the sole predictor of FMD. The effects of chronic treatment with pioglitazone were assessed in 10 subjects with type 2 diabetes. The increase in FMD significantly correlated with the decrease in SSPG. There is a significant association between vascular endothelial dysfunction and insulin resistance in type 2 diabetes. This result was supported by the effects of the insulin sensitizer, pioglitazone.     

Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease

Investigations from basic biology suggest that activation of the Rho/Rho kinase pathway reduces the bioavailability of nitric oxide (NO) and thereby promotes atherosclerosis and its clinical complications. Yet, little information is available about the relationship of the Rho/Rho kinase pathway to NO bioavailability in humans with atherosclerosis. Accordingly, we determined whether inhibition of Rho kinase augments NO bioavailability and improves endothelial function in human subjects with coronary artery disease (CAD). Thirteen CAD subjects and 16 age- and sex-matched healthy controls were randomly assigned to receive the Rho kinase inhibitor, fasudil, or placebo for 1 month each in a double-blind crossover trial. Flow-mediated, endothelium-dependent and nitroglycerin-induced, endothelium-independent vasodilation were assessed by brachial artery ultrasonography. Rho kinase activity was measured in peripheral leukocytes. Fasudil increased endothelium-dependent vasodilation in CAD subjects from 9.4+/-1.9% to 13.4+/-1.9% (P=0.001) but not in healthy controls (from 11.3+/-1.4% to 7.7+/-1.1%; P=0.07). Endothelium-independent vasodilation was not affected by fasudil in either CAD or healthy subjects. Fasudil reduced Rho kinase activity by 59+/-18% in CAD subjects (P=0.001) but not in healthy subjects (by 3+/-6%; P=0.60). The change in endothelium-dependent vasodilation achieved with fasudil relative to placebo was inversely proportional to Rho kinase inhibition (ie, greater Rho kinase inhibition was associated with larger improvement in endothelium-dependent vasodilation) (r=-0.48; P=0.01). These findings suggest that Rho/Rho kinase activation promotes endothelial dysfunction in humans with atherosclerosis. Inhibition of the Rho/Rho kinase pathway should provide a useful strategy to restore NO bioavailability in humans with atherosclerosis.     

Relation of vasodilator response of the brachial artery to inflammatory markers in patients with coronary artery disease

Endothelial dysfunction of the coronary artery is closely related to elevated levels of systemic inflammatory markers and cardiovascular events in patients with coronary artery disease (CAD). We hypothesized that patients with CAD may have a higher risk of endothelial dysfunction of the peripheral artery than patients without evidence of CAD, and that endothelial dysfunction of the peripheral artery also may be related to elevated levels of inflammatory markers. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (endothelium-independent). As inflammatory markers, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and lipid profiles were measured in patients with CAD (n = 30, 16 male and 14 female) and normal subjects without evidence of CAD (n = 45, 23 male and 22 female). Patients with CAD (Group II) showed a significantly reduced endothelium-dependent vasodilation as compared with normal subjects (Group I) (4.4 +/- 3.6 vs 7.4 +/- 6.1%, P < 0.05). However, endothelium-independent vasodilation was not significantly different between the two groups (7.7 +/- 7.1 vs 9.7 +/- 8.0%, P > 0.05). In Group II, CRP level was inversely related to endothelium-dependent vasodilation (r = -0.398, P = 0.029). In contrast, ESR level was not significantly associated to endothelium-dependent vasodilation (r = -0.113, P = 0.552). On multivariate analysis, CRP and low density lipoprotein cholesterol levels were significant independent predictors of a blunted endothelium-dependent vasodilation in Group II. Our study showed that elevated CRP level was associated with blunted endothelium-dependent vasodilation of the brachial artery in patients with CAD. Thus, identification of elevated CRP levels combined with demonstration of endothelial dysfunction of the brachial artery may have a possible clinical application for the detection of high risk CAD patients.     

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

BACKGROUND: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. METHODS: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. RESULTS: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002). CONCLUSIONS: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.     

Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation

Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors. Cardiovascular morbidity is elevated even in young women with PCOS. Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP) and endothelial dysfunction have recently been linked to development of atherosclerosis. We compared high-sensitivity (hs)CRP concentrations and endothelium dysfunction in 37 women with PCOS and 25 control subjects matched as a group for age and body mass index (BMI). Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli.Serum LH, testosterone, androstenedione, and fasting insulin levels were significantly higher in the PCOS group than the control group. The PCOS group was more insulin resistant than age- and BMI-matched control women. CRP concentrations were higher in PCOS women than the healthy control group (0.25 vs. 0.09 mg/dl). hsCRP concentrations were correlated with BMI, insulin sensitivity indices (homeostasis model assessment and quantitative insulin sensitivity check index), and endothelium-dependent vasodilation. The groups were well matched for baseline brachial artery diameter. There was a significant difference in endothelium-dependent (flow- mediated dilation) and endothelium-independent (sublingual nitroglycerin) vascular responses between the women with PCOS and the normal healthy control group (P = 0.002 and P = 0.01, respectively). Endothelium-dependent vasodilation was correlated with hsCRP concentrations and insulin resistance.In conclusion, this study is the first to demonstrate increased levels of hsCRP, endothelial dysfunction, and the relation with insulin resistance in young and normal-weight women with PCOS. Clinical strategies aimed at reducing insulin resistance may prevent early atherosclerosis in women with PCOS.     

Urinary albumin excretion is related to cardiovascular risk indicators,not to flow-mediated vasodilation,in apparently healthy subjects

Based on studies in diabetic and hypertensive populations it has been postulated that early endothelial dysfunction is the mechanism responsible for the increased cardiovascular risk in microalbuminuric subjects. We evaluated the relation between microalbuminuria and endothelial dysfunction, assessed as flow-mediated dilation of the brachial artery, in an apparently healthy population. Within the framework of the PREVEND Intervention Trial non-hypertensive and non-hypercholesterolemic subjects were recruited on the basis of reproducible microalbuminuria. Using high-resolution ultrasound, flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery was assessed to measure endothelium-dependent and endothelium-independent responses, respectively. For the current study subjects with diabetes mellitus, clinical atherosclerosis, and macroalbuminuria were excluded from the analyses. We studied 421 men and 233 women (mean age (SD) 50 (12)). Increasing levels of urinary albumin excretion were accompanied by a significant increase in age, percentage men, systolic and diastolic blood pressure, body mass index, and serum triglycerides, whereas there was no decrease of flow-mediated vasodilation or nitroglycerin-mediated vasodilation. Adjusted for age and sex, urinary albumin excretion was significantly related to systolic (r=0.19, P<0.001) and diastolic (r=0.16, P<0.001) blood pressure, body mass index (r=0.18, P<0.001), and triglycerides (r=0.13, P=0.001), but not to flow-mediated vasodilation (r=-0.01, P=0.8). In contrast to blood pressure, body mass index, and triglycerides, there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. These data suggest that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric, but otherwise healthy subjects.