High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus.

The prevalence of vascular disease among 154 diabetic patients was analysed in relation to the serum concentrations of individual lipoproteins. Overal the presence of vascular disease (59 cases) was positively associated with serum cholesterol and low-density-lipoprotein cholesterol but negatively associated with high-density-lipoprotein (HDL) cholesterol. The negative relation between HDL and vascular disease was not observed in all subgroups of diabetics. We conclude that there may be no overriding association between HDL and vascular disease in diabetics as proposed for some non-diabetic populations.     

Effects of the anti-platelet agent cilostazol on peripheral vascular disease in patients with diabetes mellitus.

Effects of cilostazol (OPC-13013, CAS 73963-72-1), a selective inhibitor of platelet cAMP-phosphodiesterase, on peripheral vascular disease in diabetes mellitus were studied. Cilostazol in a dose of 200 to 300 mg/d was administered to 5 diabetic patients with arteriosclerosis obliterans. Skin temperature of the finger and the toe, which reflects blood flow to the tissue, was selected as an objective index of cilostazol effects and measured by infra-red thermography at a constant temperature of 26 degrees C. Before administration, digital skin temperatures were low in 9 limbs of 5 patients. 200 mg/d of cilostazol significantly (p less than 0.001) increased the digital skin temperatures of 8 limbs, the increase (mean +/- SD) ranging from 29.9 +/- 1.4 degrees C to 33.2 degrees C +/- 1.2 degrees C for the average skin temperatures and from 28.7 +/- 2.1 degrees C to 33.1 +/- 1.5 degrees C for the lowest ones. An increase in the dose to 300 mg/d resulted in further elevation of skin temperatures of the digits. Cilostazol constantly elicited an increase in blood flow to the digits within the range of its therapeutic dose. This effect was observed about 1 month after initiation of administration and persisted while administration was continued. The measurement of digital skin temperatures by infrared thermography provided a noninvasive means to individualize the dosage of cilostazol and to monitor the cilostazol effect and patient complicance during long-term administration. It is concluded that cilostazol exerts a potent and steady vasodilatory effect on peripheral circulation in patients with diabetes mellitus.     

Effects of treatment for diabetes mellitus on circulating vascular progenitor cells

The circulating endothelial progenitor cells (EPCs) have an important role in angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in atherosclerosis. However, little is known about the effects of treatment of diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the relations between the number of circulating vasucular progenitor cells before and after the treatment for DM. Ten previously untreated DM patients were enrolled in this study. Blood samples were collected before and after treatment. The peripheral mononuclear cells were purified and cultured to differentiate them into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil-labeled acetylated low density lipoprotein and lectin binding. The number of SMPCs was evaluated by immunocytochemical staining of alpha-smooth muscle actin. Before treatment, the number of EPCs and SMPCs was significantly related to hemoglobin A1c and blood sugar. Serial examination revealed that improvement of glycemic control significantly increased the number of both EPCs and SMPCs. DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes.     

糖尿病合并血管病变的血小板参数变化

目的 探讨Ⅱ型糖尿病患者血小板聚集功能（PagT）与血小板计数（PLT）,血小板平均体积（MPV）变化与血管病变的关系。方法 同时测定52例Ⅱ型糖尿病患者和12例正常人血小板聚集功能与血小板计数（PLT）、血小板平均体积（MPV）、血小板分布宽度（PCT）。结果 糖尿病合并血管病变患者血小板聚集率明显增高、血小板平均体积、血小板分布宽度明显增大,与健康人比较有明显差异（P〈0．05）。结论 糖尿病患者血小板功能亢进表现为血小板聚集增高,平均体积变大。这些指标可作为糖尿病患者并发血栓性疾病的检测指标。     

Effects of propionyl-carnitine in patients with type 2 diabetes and peripheral vascular disease: results of a pilot trial

OBJECTIVE: To assess the efficacy of propionyl-carnitine (PC) in patients with type 2 diabetes and peripheral arterial disease (PAD). PATIENTS AND METHODS: This was an open pharmacodynamic study. Twenty-four obese patients with type 2 diabetes and PAD (stage IIb) were enrolled in the study. After an initial run-in period of 7 days on a low-calorie diet (1600 +/- 150 kcal/day), patients received intravenous PC (600mg in 100mL saline solution Na/K 0.9%) twice daily for 10 days (T1). RESULTS: Treatment with PC produced statistically significant increases in maximal walking distance (30%; p < 0.05) and initial claudication distance (15%; p < 0.05) in 15 and eight patients, respectively. In addition, a decrease in dosage of oral antihyperglycaemic agents was observed in 21 patients at T1. No PC-related adverse effects were reported. CONCLUSIONS: This study showed that acute intravenous administration of PC in patients with type 2 diabetes with PAD improved PAD-related symptoms as well as glycaemic control.     

Cellular and molecular mechanisms of vascular injury in diabetes--part I: pathways of vascular disease in diabetes

Diabetes-induced micro- and macrovascular complications are the major causes of morbidity and mortality in diabetic patients. While hyperglycemia is a key factor for the pathogenesis of diabetic microvascular complications, it is only one of the multiple factors capable of increasing the risk of macrovascular complications. Hyperglycemia induces vascular damage probably through a single common pathway - increased intracellular oxidative stress - linking four major mechanisms, namely the polyol pathway, advanced glycation end-products (AGEs) formation, the protein kinase C (PKC)-diacylglycerol (DAG) and the hexosamine pathways. In addition, in conditions of insulin resistance, i.e., preceding the onset of type 2 diabetes, the phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway is selectively inhibited, while the mitogen activated protein (MAP)-kinase pathway remains largely unaffected, thus allowing compensatory hyperinsulinemia to elicit pro-atherogenic events in vascular smooth muscle and endothelial cells, including increased cell proliferation, and the expression of plasminogen activator inhibitor-1, as well as of proinflammatory cytokines and endothelial adhesion molecules.     

Effects of vascular endothelial growth factor receptor inhibitor SU5416 and prostacyclin on murine lung metastasis

The majority of patients with a diagnosis of cancer die from metastatic disease. Targeting specific steps in the metastatic process has the potential to improve patient outcomes. In this study, a novel lung metastasis model was developed by injecting DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbo-cyanine perchlorate)-labeled Lewis lung carcinoma cells into the tail vein of mice. The temporal development of tumor metastases was studied in the lung, liver and spleen. Additionally, the effects of vascular endothelial growth factor receptor inhibitor SU5416 and platelet activation inhibitor prostacyclin were tested in this metastasis model. Systemically injected Lewis lung carcinoma cells present in the lung at 15 min slowly accumulated in the liver and spleen reaching a peak at 4 days. After 8 days, tumor development was only evident in the lung. Use of SU5416 or prostacyclin lowered the initial density of Lewis lung carcinoma-labeled cells in the lung by a factor 1.8 and 2.3, respectively (P<0.05). Furthermore, treatment with prostacyclin or SU5416 decreased lung weight by over 50% and the number of visible metastatic nodes by over 90% (P<0.05). Combined treatment resulted in grossly normal lung tissue. Additionally, systemic treatment with prostacyclin reduced harvested metastatic cell adherence to endothelial cells by a factor of 10 and treatment with SU5416 attenuated vascular formation (P<0.001). In conclusion, SU5416 and prostacyclin effectively attenuated metastasis formation in this model. DiI labeling is an effective technique to monitor the temporal and spatial distribution of metastatic cells.     

口服降糖药对2型糖尿病血管内皮功能的影响

目的 观察不同口服降糖药对2型糖尿病(T2DM)血管内皮功能的影响.方法 初诊T2DM患者82例,分别给予吡格列酮(A组,28例)、二甲双胍(B组,30例)或格列吡嗪(C组,24例)治疗,疗程3个月.健康体检者32例作为正常对照组(D组).检测四组血清内皮素1(ET-1)、一氧化氮(NO))和总一氧化氮合酶(T-NOS)的水平.结果 与D组比较,A组、B组、C组ET-1水平升高,NO、T-NOS水平下降(P＜0.05).与治疗前比较,A组、B组治疗后ET-1水平降低,而NO、T-NOS水平明显升高(P＜0.05).结论 吡格列酮与二甲双胍具有更好的改善血管内皮功能的作用.     

2型糖尿病患者血管病变与血小板-白细胞聚集体的相关性

目的 探讨2型糖尿病患者血小板-白细胞聚集体(PLA)的变化及其与血管病变的关系.方法 应用流式细胞术检测71例糖尿病患者组及正常对照组34例外周血中血小板-中性粒细胞聚集体(PNA)、血小板-单核细胞聚集体(PMA)的表达水平.结果 糖尿病组的PNA和PMA的阳性表达率分别为(25.17±8.89)%和(40.22±18.64)%,均明显高于对照组的(15.43±4.70)%和(18.44±6.61)%(P＜0.01).糖尿病合并血管病变组患者的PNA、PMA比单纯糖尿病组患者升高更明显(P＜0.05和P＜0.01);血管病变损伤区域≥3和≥2时,PNA及PMA的百分率明显高于无血管病变组(P＜0.01).结论 2型糖尿病患者的PLA明显升高,与糖尿病血管病变具有相关性.PMA的升高可作为反映糖尿病血管病变的标记.     

Advances in reducing the burden of vascular disease in type 2 diabetes

1. The epidemic of diabetes is accelerating and the World Health Organization estimates that the number of people affected worldwide will grow from 171 million in 2000 to 366 million by 2030. 2. The main causes of death and disability in individuals with type 2 diabetes are macrovascular and microvascular disease, and blood pressure is one of the main determinants of vascular complications in this population. 3. While randomized trials have demonstrated that blood pressure lowering reduces vascular complications in subjects with type 2 diabetes and hypertension, ADVANCE was designed to determine whether the addition of a fixed combination of perindopril and indapamide, on top of comprehensive and effective cardiovascular treatments and glucose control therapy, would produce further benefits, irrespective of the initial blood pressure. 4. The blood pressure lowering arm of ADVANCE has demonstrated that the simple addition of the fixed combination of perindopril and indapamide compared to matching placebo, significantly reduces combined macrovascular and microvascular complications by 9%, all-cause mortality by 14% and cardiovascular death by 18%. It also reduces total coronary events by 14% and all renal events and microalbuminuria by 21%. 5. Similar benefits were observed in participant sub-groups characterized by age, sex, baseline blood pressure, previous vascular diseases and concomitant cardiovascular therapy including blood pressure lowering therapy. 6. Successful implementation of this treatment, with a single combination tablet of perindopril and indapamide, should be practical and affordable in most clinical settings worldwide and has the capacity to save countless lives and to reduce the burden of coronary disease and renal disease burden among millions of people with type 2 diabetes.     

卡维地洛对高血压病并发2型糖尿病患者血管内皮功能及胰岛素抵抗的影响

目的:探讨卡维地洛对高血压合并糖尿病患者血管内皮功能及胰岛素抵抗的影响。方法:经2周导入期后熏将41例高血压合并2型糖尿病患者熏随机分为卡维地洛组(21例)和美托洛尔组(20例)。治疗前及治疗6月后熏采静脉血测定空腹胰岛素、空腹血糖熏计算胰岛素敏感性指数;采用高分辨率超声检测反应性充血和硝酸甘油介导的肱动脉舒张功能。结果:卡维地洛治疗6月后,患者收缩压和舒张压均有效下降熏空腹胰岛素降低,胰岛素敏感指数显著升高熏反应性充血和硝酸甘油介导的血管舒张功能均明显改善。美托洛尔治疗后,空腹血糖和空腹胰岛素均轻度升高,胰岛素敏感指数降低,但差异均不具有统计学意义;反应性充血和硝酸甘油介导的血管舒张功能均无明显变化。结论:卡维地洛可有效降低高血压合并2型糖尿病患者的血压,改善胰岛素抵抗及肱动脉内皮依赖性及非内皮依赖性的血管舒张功能。     

Effects of modifying triglycerides and triglyceride-rich lipoproteins on cardiovascular outcomes

Elevated levels of triglycerides (and triglyceride-rich lipoproteins) are increasingly being recognized as treatment targets to lower cardiovascular risk in certain patient subgroups, including individuals receiving HMG-CoA reductase inhibitors (statins). Evidence suggests that these agents reduce the risk of coronary events more markedly in patients with elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C). Further, intensive long-term statin therapy that reduces both low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL and triglycerides to <150 mg/dL results in a decreased risk of cardiovascular events compared with more moderate statin treatment. Long-term therapy with fibric-acid derivatives, which lower triglycerides and raise HDL-C, appears to reduce mortality in patients with elevated triglycerides and/or those experiencing the most marked reductions in triglycerides on therapy. However, randomized clinical trials involving fibrates have not shown consistent benefit. Niacin (nicotinic acid), which is the most effective available medication for raising HDL-C and also lowers triglycerides, has not been as extensively studied as fibrates in long-term randomized controlled trials. Initial reports (eg, Coronary Drug Project) demonstrated a reduction in coronary disease but not total mortality in patients randomized to niacin. However, a 15-year follow-up demonstrated that all-cause mortality was significantly reduced in those initially randomized to niacin. At the pathophysiologic level, elevated triglycerides and triglyceride-rich lipoproteins are recognized as potential factors in driving atherosclerotic progression, particularly in mild-to-moderate lesions. Elevated triglycerides also constitute a plausible therapeutic target in certain patients with coronary heart disease (and/or insulin resistance) but without profound LDL-C elevations. The foregoing and other evidence has led consensus panels to lower the upper limit for "normal" triglycerides to 150 mg/dL. Adequately powered randomized controlled trials that specifically assess the effects of lowering triglycerides and raising HDL-C, and trials that target individuals with high triglycerides and low HDL-C, may provide data for recommending specific treatment targets for triglycerides and HDL-C, as well as effective and well-tolerated therapies to achieve these goals.     

Effects of coffee on plasma lipids, lipoproteins and apolipoproteins

The acute effects of coffee, cigarette smoking and alcohol on serum lipids, lipoproteins and thromboxane B2 production by platelets were studied in nine healthy volunteers who were non-drinkers of coffee and alcohol and non-smokers. They received, in a single administration, coffee (containing 200 mg of caffeine), alcohol (0.50 ml/kg body wt), or smoked two cigarettes. No differences were observed between baseline and 15, 60 and 80 min values for plasma cholesterol, triglycerides, HDL cholesterol, plasma apolipoproteins A-I and B and thromboxane B2 production. Chronic coffee consumption also did not affect either plasma lipoprotein profile or the interaction of low density lipoproteins with cellular receptors in a group of healthy individuals. These results suggest that coffee itself does not affect acutely the plasma lipoprotein profile in healthy man. This was also true in heavy coffee drinkers.     

吡格列酮对糖尿病大鼠血管内皮功能的影响

目的观察吡格列酮（Pioglitzone,PIO）对伴胰岛素抵抗的实验性2型糖尿病（Type 2 diabetes mellitus,T2DM）大鼠血管内皮功能、超微结构及炎症因子的影响。方法建立伴胰岛素抵抗的T2DM大鼠模型,随机分为DM组和PIO组,测定PIO治疗6周前后的各项指标,电镜下观察主动脉血管内皮细胞结构的变化。结果治疗6周后,与DM组相比,PIO组空腹血糖、糖化血红蛋白、胰岛素水平、胰岛素抵抗指数、胰岛素敏感指数及C反应蛋白均下降,血一氧化氮水平上升,差异均有显著性,但两组间血内皮素水平无显著差异。DM组主动脉血管内皮细胞线粒体肿胀,部分空泡变;PIO组仅发生轻度病理改变。结论PIO可以改善T2DM大鼠胰岛素抵抗,降低血糖,减轻主动脉形态学的损害,其机制可能与抗炎及改善血管内皮功能有关。     

老年2型糖尿病患者并发心脑血管病变危险因素分析

目的：探讨老年2型糖尿病患者并发心脑血管病变危险因素。方法：收集126例老年2型糖尿病患者的临床资料,分为无心脑血管病变组（对照组）54例,心脑血管病变组（观察组）72例,对两组的相关资料进行统计学分析。结果：两组患者年龄、病程、吸烟史存在显著差异,SBP、2hPG、TC、HDL、LDL和UA水平存在显著差异。结论：老年2型糖尿病患者并发心脑血管病变与年龄、病程及血压、血脂及血糖控制不良等因素有关。     

糖尿病下肢血管病变药物治疗综述

糖尿病下肢血管病变为糖尿病常见的慢性并发症之一。及早给予药物治疗不仅能有效缓解症状,还能积极预防血管并发症的发生,延缓疾病的发展,降低截肢率,对糖尿病下肢血管病变的预后具有重要意义。本文综述糖尿病下肢血管病变的药物治疗现状。     

彩色多普勒超声对糖尿病下肢血管病变的诊疗价值探讨

目的探讨彩色多普勒超声对糖尿病(DM)下肢血管病变的诊疗价值。方法选取DM下肢血管病变患者60例作为DM组,另选取同期无DM下肢血管病变患者60例作为对照组。比较2组下肢彩色多普勒超声检查结果。结果 DM组管腔内膜光滑率低于对照组,下肢动脉斑块发生率高于对照组,差异均有统计学意义(P<0.05)。2组下肢动脉狭窄分布情况比较差异无统计学意义(P>0.05)。结论彩色多普勒超声能准确直观的对下肢动脉硬化定性并判断病变部位和严重程度,对DM下肢动脉病变的诊疗有重要价值。