新诊断2型糖尿病患者血清血管内皮细胞钙粘蛋白的变化及其意义

目的观察新诊断2型糖尿病患者血清血管内皮细胞钙粘蛋白等指标的变化。方法选择35例新诊断2型糖尿病患者为观察组,36例正常体检者为健康对照组。测定血清中血管内皮功能指标：血管内皮细胞钙粘蛋白（VE-cadherin）、内皮素（ET-1）、一氧化氮（NO）及一氧化氮合酶（NOS）。并同时测定空腹血糖（FBG）、餐后2 h血糖（P2hBG）、糖化血红蛋白（HbA1c）、体重指数（BMI）、血脂、收缩压（SBP）、舒张压（DBP）。结果糖尿病组血管内皮细胞钙粘蛋白水平高于健康对照组,一氧化氮低于健康对照组,差异有统计学意义（P〈0.05）。相关分析显示,血管内皮细胞钙粘蛋白与糖化血红蛋白呈正相关,一氧化氮与糖化血红蛋白呈负相关,一氧化氮和一氧化氮合酶呈正相关,一氧化氮合酶和内皮素呈负相关。结论新诊断2型糖尿病患者血管内皮功能已受损,炎症、血管内皮细胞钙粘蛋白复合体和一氧化氮途径较早受损可能共同介导糖尿病内皮功能损伤。     

2型糖尿病合并脑卒中患者VEGF、NO、ET-1的变化及其相关性

目的探讨2型糖尿病合并脑卒中患者血管内皮生长因子(VEGF)、一氧化氮(NO)、内皮素1(ET-1)的变化及其与糖化血红蛋白(HbAlc)之间的关系。方法以无糖尿病及脑卒中的患者为对照组(n=30),以2型糖尿病合并脑卒中的患者为实验组(n=52),检测2组的VEGF、NO、ET-1及HbA1c水平,分析2组之间各项指标的差异以及实验组反映血管内皮功能的3项指标与HbAlc的相关性。结果实验组的VEGF、ET-1高于对照组(P<0.01,P<0.05),NO低于对照组(P<0.01);实验组的HbA1c为(7.5±1.3)%,对照组为(5.5±0.7)%,2组比较差异有统计学意义(P<0.01)。实验组HbA1c与VEGF呈正相关(r=0.599,P<0.01),与NO呈负相关(r=-0.470,P<0.01),与ET-1呈正相关(r=0.601,P<0.01)。结论 2型糖尿病合并脑卒中患者血管内皮功能降低,其可能与血糖控制欠佳有关。     

血管内皮细胞钙粘蛋白在2型糖尿病患者中的变化及意义

目的 探讨2型糖尿病(T2DM)患者血管内皮细胞钙粘蛋白(VEC)以及内皮素(ET)、一氧化氮(NO)、一氧化氮合酶(NOS)等的变化及其意义.方法 对T2DM患者85例和健康人80例,测定VEC、ET、NO、NOS水平及血糖等,分析VEC等变化及其意义.结果 T2DM组糖化血红蛋白( HbA1c )、空腹血糖(FBG)、VEC、ET明显高于健康人组;VEC与HbA1c 、EF呈正相关,NO与NOS呈正相关.结论 血管内皮功能障碍可能是导致血管病变的原因,VEC、ET、NO、NOS可能参与T2DM患者血管病变的发生和发展,可作为T2DM大血管并发症发生的预测和检测指标.     

老年OSAHS伴2型糖尿病患者血ET-1/NO比值变化及其与血糖和睡眠监测指标的相关性分析

目的探讨检测老年阻塞性睡眠呼吸暂停低通气综合征(OSAHS)伴2型糖尿病患者血内皮素-1(ET-1)/一氧化氮(NO)比值变化及其与血糖和睡眠监测指标的相关性分析,为临床从血管内皮功能角度干预OSAHS伴2型糖尿病患者提供依据。方法选取某院经多导睡眠监测(PSG)及空腹血糖检测确诊的老年OSAHS伴2型糖尿病患者78例,单纯老年2型糖尿病患者41例,单纯老年OSAHS患者37例,所有患者均检测血浆ET-1及血清NO,计算ET-1/NO比值,比较三组ET-1/NO比值变化及其与血糖和睡眠监测指标的相关性。结果①与2型糖尿病组患者比较,老年OSAHS伴2型糖尿病组、老年OSAHS组患者SpO_2、ET-1/NO明显降低,AHI增高(P0.05),其中,老年OSAHS伴2型糖尿病组患者SpO_2、AHI、ET-1/NO改变更为显著(P0.05)。②直线相关分析显示,老年OSAHS伴2型糖尿病患者血ET-1/NO比值与血糖呈负相关(r=-0.612,P0.05),与AHI呈负相关(r=-0.646,P0.05)。结论老年OSAHS伴2型糖尿病患者与单纯老年OSAHS患者和老年糖尿病患者比较,血糖和睡眠监测指标紊乱更为严重,血ET-1/NO比值显著降低,提示老年OSAHS伴2型糖尿病患者血管内皮受损程度更加严重。     

糖尿病肢体动脉闭塞症患者血管内皮功能的超声检测

目的探讨超声检查在糖尿病肢体动脉闭塞症中判断血管内皮功能障碍的价值。方法运用高频超声检测60例糖尿病肢体动脉闭塞症患者和20例正常对照者的血管内皮功能,并测定内皮素-1(ET-1)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-Keto-PGF1α)及一氧化氮(NO)的浓度。结果糖尿病肢体动脉闭塞症患者内皮依赖性舒张功能(EDD)随病变进程逐渐降低,三期患者非内皮依赖性舒张功能(EID)也下降。患者ET-1、TXB2水平高于对照组,NO、6-Keto-PGF1α水平低于对照组,且EDD与ET-1、TXB2水平呈负相关,与NO、6-Keto-PGF1α水平呈正相关。结论超声检查对血管内皮功能进行检测具有重要的临床意义。     

2型糖尿病一级亲属血管内皮依赖性舒张功能和血浆内皮素的变化

目的观察2型糖尿病糖耐量正常一级亲属(FDR s)血管内皮功能受损情况及血浆内皮素(ET-1)水平的变化。方法选择61例糖耐量正常的2型糖尿病一级亲属及39例健康对照者,测定其血管内皮功能、ET-1水平,空腹胰岛素(FINS)及血脂等。结果FDR s组血浆ET-1水平显著高于对照组(P<0.05),由肱动脉反应性充血介导的血管舒张程度较对照组明显降低,具有显著性差异(P<0.05),而两组间由硝酸甘油介导的血管舒张程度和基础内径与对照组相比无显著性差异(P>0.05)。结论2型糖尿病糖耐量正常一级亲属存在血管内皮功能障碍。     

格列齐特联合DPP-4抑制剂治疗2型糖尿病患者及对胰岛素抵抗指数的影响

目的探讨格列齐特联合二肽基肽酶(DPP-4)抑制剂对2型糖尿病(T2DM)患者血糖控制及胰岛素抵抗指数(HOMAIR)的影响。方法选取2017年1月～2018年12月我院收治的T2DM患者94例,简单随机化分对照组和观察组各47例。对照组口服DPP-4抑制剂,观察组基于对照组口服格列齐特,连续治疗3个月。统计两组不良反应,对比治疗前后糖化血红蛋白(HbA1c)、餐后2h血糖(2hBG)、HOMA-IR及血清内皮素-1(ET-1)、总一氧化氮合酶(tNOS)。结果治疗后观察组2hBG、Hb A1c、HOMA-IR水平均低于对照组,差异均有统计学意义(P0.05);治疗后观察组血清ET-1水平较低,tNOS水平均高于对照组,差异均有统计学意义(P0.05);观察组不良反应发生率为8.51%,对照组为12.77%,两组比较差异无统计学意义(P0.05)。结论格列齐特联合DPP-4抑制剂应用于T2DM患者,可改善血管内皮功能,控制血糖,降低HOMA-IR,且安全性高。     

血糖波动对初诊2型糖尿病患者血管内皮功能和C-反应蛋白的影响

[目的]探讨血糖波动对初诊2型糖尿病患者血管内皮功能和C-反应蛋白(CRP)的影响.[方法]选取在本院进行治疗的60例初诊2型糖尿病患者为观察组,同期健康体检的60名健康人为对照组,将两组人员的内皮依赖性血管舒张功能(EDD)、动脉内膜中层厚度(IMT)及血清内皮素(ET)、一氧化氮(NO)、血管性血友病因子(vWF)、CRP水平进行比较.[结果]观察组的EDD低于、IMT高于对照组,ET、vWF及CRP均高于对照组,NO则低于对照组,且差异均有显著性(P均＜0.05),观察组上述指标中血糖波动较大及伴有高血压者的波动幅度要大于波动幅度较小和不伴有高血压者(P均＜0.05).[结论]血糖波动对初诊2型糖尿病患者血管内皮功能和CRP的影响较大.     

高血压患者血管内皮功能及颈动脉内膜中层厚度与室间隔厚度的关系

目的探讨高血压患者室间隔厚度与血管内皮功能及颈动脉内膜中层厚度的关系。方法选择中老年高血压患者85例,应用彩色多普勒超声检测心脏室间隔厚度、肱动脉内皮依赖性舒张功能(FMD)及颈动脉内膜中层厚度(IMT),根据室间隔厚度分为室间隔肥厚组和室间隔正常组,并测定一氧化氮(NO)、内皮素-1(ET-1)、空腹血糖、总胆固醇、低密度脂蛋白等生化指标,同时选择我院体检中心健康人群30名作为健康对照组。结果室间隔肥厚组FMD、NO含量较室间隔正常组及对照组显著降低,颈动脉IMT明显增厚,ET-1浓度明显增高,差异有统计学意义(P0.05)。相关性分析提示室间隔厚度与IMT(r=0.533)、ET-1(r=0.673)呈正相关,与FMD(-0.628)、NO(r=-0.629)呈负相关,颈动脉IMT与肱动脉FMD呈负相关(r=-0.706)。结论高血压患者存在血管功能障碍,且室间隔肥厚患者血管内皮功能及颈动脉损害程度更严重。     

益气养阴活血法对2型糖尿病患者血管内皮功能的保护作用

目的:观察益气养阴活血中药复方丹蛭降糖胶囊对2型糖尿病血管病变患者内皮型一氧化氮合酶(e NOS)、内皮素转换酶(ECE)、同型半胱氨酸(Hcy)的影响,探讨丹蛭降糖胶囊保护血管内皮功能的作用机制。方法:将60例2型糖尿病患者采用随机、平行对照法,分对照组30例,治疗组30例,2组均给予常规降糖治疗,治疗组加用具益气养阴活血功效的中药丹蛭降糖胶囊,每次5粒,每日3次,疗程24周,观察治疗前后血糖、糖化血红蛋白、血脂、内皮型一氧化氮合酶(e NOS)、内皮素转换酶(ECE)、同型半胱氨酸(Hcy)水平。结果:治疗后治疗组e NOS、ECE、Hcy改善优于对照组(P0.05)。结论:丹蛭降糖胶囊能有效保护T2DM血管内皮功能,防治糖尿病血管病变。     

2型糖尿病患者后代内皮细胞型一氧化氮合酶基因多态性研究

背景2型糖尿病患者内皮细胞型一氧化氮合酶(endothelial constitutivenitric oxide synthase,ecNOS)的第四内含子的a等位基因(4a等位基因)频率增高且与血管内皮功能减低有关.目的探讨2型糖尿病和糖耐量正常的2型糖尿病一级亲属ecNOS基因多态和血浆一氧化氮并探讨他们的关系.设计以诊断为依据,非随机对照试验.地点、对象和方法正常对照组67例为河北省人民医院健康查体并自愿参加研究者,男33例,女34例;一级亲属组为本院代谢门诊就诊的2型糖尿病患者子女98例,男48例,女50例;糖尿病组为本院老年内分泌科就诊的2型糖尿病患者85例,男40例,女45例.纳入标准符合1999年WHO 2型糖尿病诊断标准.排除标准无糖尿病神经病变及血管病变;无血缘关系;无严重高脂血症等.应用PCR扩增技术测定ec-NOS基因型,用硝酸还原酶法测定一氧化氮.主要观察指标3组研究对象的ecNOS基因型、一氧化氮水平以及空腹胰岛素、总胆固醇、三酰甘油、体质量指数、腰臀比、空腹血糖及血红蛋白.结果①糖尿病组和一级亲属组与对照组相比a/a+a/b基因型频率和4a等位基因频率呈增高趋势,但差异无显著性意义(P＞0.05).②对照组、一级亲属组、糖尿病携带4a等位基因者的血浆一氧化氮水平[(68.00±15.9),(60.75±17.64),(61.63±18.26)μmol/L]显著低于不带4a等位基因者[(98.30±25.1),(83.70±26.37),(75.15±29.38),t=-3.289,-3.432,P＜0.01,t=-2.432,P＜0.05].结论2型糖尿病和糖耐量正常的2型糖尿病一级亲属血浆一氧化氮降低存在基因依赖性.     

益肾养阴活血方对冠心病合并2型糖尿病患者血管内皮功能及血糖水平的影响

目的探讨益肾养阴活血方对冠心病合并2型糖尿病患者血糖、血管内皮功能的影响。方法将某院收集的109例确诊为冠心病合并2型糖尿病患者作为研究对象并按照随机数表法的分组方法分为两组,西药组54例实施西药氯吡格雷治疗,联合组55例在西药治疗的基础上增加益肾养阴活血方治疗。治疗结束后对比两组患者一氧化氮(NO)、血管性血友病因子(vWF)、血浆内皮素-1(ET-1)、空腹血糖值、餐后2 h血糖值及不良反应等指标。结果联合组患者的临床疗效高于西药组(P<0.05);治疗后联合组血管内皮功能指标vWF、ET-1水平高于西药组,NO低于西药组(P<0.05);联合组的空腹血糖值及餐后2 h血糖值低于西药组(P<0.05);两组不良反应对比差异无统计学意义(P>0.05)。结论益肾养阴活血方治疗冠心病合并2型糖尿病效果优越,可提高患者血管内皮功能,降低血糖水平,不良反应少。     

利拉鲁肽联合吡格列酮对肥胖型2型糖尿病患者糖脂代谢、血管内皮功能、血糖波动程度的影响

目的 探讨利拉鲁肽联合吡格列酮对肥胖型2型糖尿病(T2DM)患者糖脂代谢、血管内皮功能、血糖波动程度的影响.方法 选取2017年4月至2020年8月我院收治的69例肥胖型T2DM患者作为研究对象,根据用药方案不同将其分为对照组(n=34)和观察组(n=35).对照组采用常规治疗+吡格列酮,观察组在对照组基础上加用利拉鲁...     

Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes

BACKGROUND: Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function. METHODS: Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group. RESULTS: Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body-mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls. CONCLUSION: Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.     

Nitrotyrosine: new findings as a marker of postprandial oxidative stress

Oxidative stress plays an important role in diabetic vascular complications. It has been shown that an imbalance in the ratio of nitric oxide to superoxide anion due to a prevalence of the superoxide anion leads to an alteration in vascular reactivity. Under these conditions an increase in peroxynitrite (ONOO-) production, resulting from the reaction between nitric oxide (NO) and superoxide (O2-), may be hypothesised. ONOO- is responsible for nitration of tyrosine residues in proteins; therefore the presence of nitrotyrosine (NT) in plasma proteins is considered indirect evidence of ONOO- production. NT has been found in the plasma of patients with diabetes, but it is not detectable in the plasma of healthy controls. NT plasma values are correlated with plasma glucose concentrations, and further studies exploring the effects of acute hyperglycaemia on NT formation confirmed that NT is produced both in normal subjects during hyperglycaemic clamp and in working hearts from rats during hyperglycaemic perfusion. Postprandial hypertriglyceridemia and hyperglycaemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridaemia and hyperglycaemia induce an endothelial dysfunction through an oxidative stress; however, the specific roles of these two factors are matters for debate. In a clinical study, high-fat load and glucose alone each produced a decrease in endothelial function and an increase in NT in normal subjects and patients with diabetes. These effects were more pronounced when high-fat load and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters, but reduced the effects of high-fat load, glucose alone, and both high-fat load and glucose on endothelial function and NT Long-term simvastatin treatment was accompanied by a smaller increase in postprandial triglycerides, which was followed by smaller variations in endothelial function and NT. This study showed an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycaemia on endothelial function, suggesting oxidative stress as a common mediator of these effects. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug. These studies indicate that ONOO- is generated in diabetes, suggesting the possible involvement of ONOO- in the development of diabetic complications.     

Type 2 diabetes mellitus in mice aggravates the renal impact of hemorrhagic shock

ABSTRACT: The objectives of this study were to determine whether type 2 diabetic mice would exhibit a more severe renal impact of hemorrhagic shock (HS) based on a recently described model of acute kidney injury and to determine the impact of HS on renal responses to hypoxia. We induced HS or sham procedure in type 2 diabetic and obese db/db mice. Creatininemia, glomerular filtration rate, urine output, histologic injury score, and kidney inductible molecule 1 mRNA were used to investigate the renal impact of HS. Tissular hypoxia and its impact were quantified using pimonidazole immunostaining and mRNA of hypoxic inducible factor, vascular endothelial growth factor receptors 1 and 2, Tie-2, endothelial nitric oxide synthase, and inducible nitric oxide synthase. Diabetic mice exhibiting mild diabetic nephropathy express hypoxic signals at baseline. The renal impact of HS was more severe in diabetic mice, with a worsening of tissular hypoxia and an altered response to hypoxia. Furthermore, endothelial nitric oxide synthase was highly overexpressed in diabetic shocked mice when compared with nondiabetic shocked mice. Renal impact of HS in type 2 diabetic mice is more intense than in nondiabetic ones. Preexisting hypoxia during diabetes could result in a renal preconditioning that modifies endothelial and tissular responses to acute kidney injury.     

改善血糖漂移对老年糖尿病患者血管内皮功能的影响

目的探讨动态血糖监测系统监测下控制血糖漂移对老年2型糖尿病患者血管内皮功能的影响。方法93例2型糖尿病患者,佩戴动态血糖监测系统监测3d,根据监测结果分为血糖高漂移组59例和血糖低漂移组34例,比较2组血浆内皮素水平和血生化指标。血糖高漂移组患者继续给予动态血糖监测系统监测,并根据监测结果及时调整治疗方案,持续治疗4周,比较治疗前、后血糖漂移指标及内皮素水平和血生化指标变化。结果血糖高漂移组内皮素水平高于血糖低漂移组（P〈0.05）;血糖高漂移组治疗后血糖标准差、最大血糖漂移幅度、平均血糖漂移幅度及内皮素水平较治疗前降低（P〈0.05）;多元逐步回归分析结果显示,血糖高漂移组最大血糖漂移幅度与内皮素水平呈正相关（β=5.156,P=0.011）。结论动态血糖监测系统监测下改善血糖漂移,可改善老年2型糖尿病患者血管内皮功能。     

内皮型一氧化氮合酶基因多态性与2型糖尿病并发勃起功能障碍的相关性研究

目的探讨内皮型一氧化氮合酶（ecNOS）基因内含子4可变数目串联重复序列（4VNTR）插入／缺失多态性（4b／a）和外显子7单核苷酸多态性（G894T）与男性2型糖尿病（T2DM）并发勃起功能障碍（DED）的关联性。方法提取108例男性T2DM患者、94例DED患者及100例男性健康人（NC）的基因组DNA,用聚合酶链反应-可变数目串联重复序列法（PCR）测定4VNTR多态性;聚合酶链反应-限制片段长度多态性法（PCR-RFLP）测定G894T多态性。结果DED组吸烟史、糖尿病周围血管病变（DPA）均高于T2DM组（P〈0．01）;NC组、T2DM组、DED组3组低密度脂蛋白胆固醇（LDL-C）分别为（2．37±0．86）mmol／L、（2．85±0．74）mmol／L、（3．12±0．92）mmol／L,糖化血红蛋白（HbAlc）分别为（6．40±0．64）％、（5．06±1．09）％、（7．32±0．66）％（P〈0．05或〈0．01）;T2DM组、DED组甘油三酯（TG）和总胆固醇（TC）均高于NC组,TG为（1．76±0．66）mmol／L、（1．89±0．52）mmol／Lvs（1．35±0．54）mmol／L,TC为（4．95±0．77）mmol／L、（5．06±1．09）mmol／Lvs（4．31±0．86）mmol／L（均P〈0．01）;NC组、T2DM组、DED组3组间4VNTR多态性基因型（x^2=7．142,P=0．028）、等位基因（x^2=9．929,P=0．007）和G894T多态性基因型（x^2=2．118,P=0．002）、等位基因（x^2=15．468,P=0．000）频率分布差异均有统计学意义。logistic回归分析显示携带ecNOS4a等位基因（OR=2．282,P=0．012）、T等位基因（OR=5．217,P=0．002）以及合并DPA（OR=3．958,P=0．006）的T2DM患者并发DED的危险性更高。结论携带ecNOS基因内含子4a等位基因、894位点T等位基因以及合并DPA是男性T2DM并发DED的独立危险因素。     

Role of nitric oxide in diabetic complications

Diabetic vascular disease is accompanied by decreased formation of the vasodilators, nitric oxide (NO), and prostacyclin and increased formation of vasoconstrictor eicosanoids, which exacerbate the progression of vascular disease. Similarities between the dysfunction introduced by short-term effects of elevated glucose and long-term effects of diabetes suggest that the alteration in endothelial factors in diabetes primarily results from exposure of endothelial cells to elevated glucose, although undoubtedly hyperlipidemia contributes as well. A key alteration in endothelial cell phenotype is increased formation of reactive oxygen species. This is in part due to uncoupling of endothelial NO synthase such that it generates superoxide anion in addition to NO. This is responsible for NO synthase to produce peroxynitrite, a damaging molecule. Peroxynitrite inactivates prostacyclin synthase leading to the accumulation of inflammatory and prothrombotic eicosanoids. This not only helps to explain the impairment of endothelial vasodilator mechanisms, but also increased progression of vascular disease. Many of these cellular abnormalities can be prevented by adequate scavenging of oxygen-derived free radicals or by blocking the actions of the eicosanoids at thromboxane (TP) receptors. Exposure to elevated glucose also gives rise to oxidants in smooth muscle, and recent studies indicate that oxidation of cysteine thiols under these conditions may prevent physiological NO signaling. As a result, the responsiveness to NO is impaired and accounts in part for abnormal endothelium-dependent vasodilation.