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浙江大学学报（医学版） 2006年第3期35卷 233-237页

作者：李红浙江大学医学院附属第一医院内分泌科浙江杭州310003

糖尿病微血管病变是糖尿病致死致残的主要原因之一,严重影响糖尿病患者的生存质量。其发病机制尚未完全明了,目前认为主要与多元醇通路活跃、氧化应激增加、糖基化终产物形成及蛋白激酶C通路激活有关。以发病机制为靶点的治疗可能会为... 详细信息

糖尿病微血管病变是糖尿病致死致残的主要原因之一,严重影响糖尿病患者的生存质量。其发病机制尚未完全明了,目前认为主要与多元醇通路活跃、氧化应激增加、糖基化终产物形成及蛋白激酶C通路激活有关。以发病机制为靶点的治疗可能会为预防和延缓糖尿病微血管病变的发生发展带来新的希望。

关键词：糖尿病/并发症糖尿病血管病变/病因学糖尿病血管病变/病理生理学糖尿病血管病变/药物疗法

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Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus - A serial intravascular ultrasound study

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第5期36卷 1529-1535页

作者： Takagi, T Akasaka, T Yamamuro, A Honda, Y Hozumi, T Morioka, S Yoshida, K Kobe Gen Hosp Div Cardiol Chuo Ku Kobe Hyogo Japan Kawasaki Med Sch Dept Internal Med Div Cardiol Kurashiki Okayama 70101 Japan

OBJECTIVES The aim of the present study was to determine whether troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus (NIDDM). BACKGROUNND Increased in-stent restenosis in patients with diabetes mellitus is due to accelerated neointimal tissue proliferation after coronary stent implantation. Troglitazone inhibits intimal hyperplasia in experimental animal models. METHODS We studied 62 stented lesions in 52 patients with plasma glucose levels (PG) greater than or equal to 11.1 mmol/liter at 2 h after 75 g oral glucose load. The study patients were randomized into two groups: the troglitazone group of 25 patients with 29 stents, who were treated with 400 mg of troglitazone, and the control group of 27 patients with 33 stents. All patients underwent oral glucose tolerance tests before and after their six-month treatment period. The sum of PG (Sigma PG) and the sum of insulin levels (Sigma IRI) were measured. Serial (postintervention and at six-month follow-up) intravascular ultrasound studies were performed. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback. Stent areas (SA), lumen areas (LA), and intimal areas (IA = SA - LA) were measured and averaged over a number of selected image slices. The intimal index was calculated as intimal index = averaged IA/averaged SA x 100%. RESULTS There were no differences between the two groups before treatment in Sigma PG (31.35 +/- 3.07 mmol/liter vs. 32.89 +/- 4.87 mmol/liter, respectively, p = 0.2998) and Sigma IRI (219.6 +/- 106.2 mU/liter vs. 209.2 +/- 91.6 mU/liter, respectively, p = 0.8934). However, reductions in Sigma PG at the six-month follow-up in the troglitazone group were significantly greater than those in the control group (-21.4 +/- 8.846 vs. -4.5 +/- 7.4%, respectively, p < 0.0001). Likewise, decreases in IRI were greater in the troglitazone-treated group (-31.4 +/- 17.9% vs. -

关键词：细胞分裂色满类/药理学冠心病/并发症冠心病/诊断显像冠心病/药物疗法冠心病/病理学糖尿病 2型/并发症糖尿病血管病变/诊断显像糖尿病血管病变/药物疗法糖尿病血管病变/病理学降血糖药/药理学支架噻唑类/药理学噻唑烷二酮类血管内膜/药物作用血管内膜/病理学超声检查介入性女(雌)性人类男(雄)性中年人

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Long-term effects of the endothelin_A receptor antagonist LU 135252 and the angiotensin-converting enzyme inhibitor trandolapril on diabetic angiopathy and nephropathy in a chronic type I diabetes mellitus rat model

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期293卷 351-359页

作者： Dhein, S Hochreuther, S Spring, CAD Bollig, K Hufnagel, C Raschack, M Univ Halle Wittenberg Inst Pharmacol D-06097 Halle Germany Univ Cologne Inst Pharmacol Cologne Germany Knoll AG D-6700 Ludwigshafen Germany

Diabetic angiopathy is a serious problem in antidiabetic therapy. We wanted to investigate whether treatment with the endothelin(A) receptor antagonist LU 135252 or with the angiotensin-converting enzyme inhibitor trandolapril might prevent angiopathy in long-term type I diabetes mellitus. Six groups of male Wistar rats were investigated: untreated age-matched control rats, healthy controls treated with trandolapril (0.3 mg/kg), healthy controls treated with LU 135252 (100 mg/kg), untreated diabetic rats, and diabetic rats treated with either trandolapril or LU 135252. Rats were rendered diabetic by injection of streptozotozin. Duration of the disease was 6 months. Thereafter, rats were sacrificed, and hearts, kidneys, and a mesenterial loop were removed. Hearts and kidneys were processed histologically;the mesenterial loop was perfused with saline at constant pressure for investigation of microvessels using microvideoangiometry while treated with either 30 mM KCl, 1 mu M acetylcholine, or 1 mM sodium nitroprusside. All diabetic rats developed hyperglycemia without differences among these three groups. Diabetic rats exhibited marked anemia, which was significantly antagonized by both treatments. The heart capillaries/muscle fibers ratio was decreased significantly in diabetic animals, which was prevented fully by both treatments. Renal glomerular diameter was increased in diabetic rats. This was significantly antagonized by LU 135252 but not by trandolapril. Deposition of homogeneous eosinophilic material within the glomeruli was nearly completely prevented by LU 135252. The acetylcholine-induced vasodilation in mesenteric microvessels was significantly attenuated in diabetic rats, which was significantly antagonized by both treatments. We conclude that both angiotensin and endothelin seem to contribute to the development of diabetic angiopathy and that, in addition to angiotensin-converting enzyme inhibition, blockade of endothelin(A) receptors may be an interestin

关键词：血管紧张素转换酶抑制药/治疗应用血糖/代谢血压/药物作用血管/病理学体重/药物作用糖尿病实验性/药物疗法糖尿病实验性/病理学糖尿病实验性/病理生理学糖尿病血管病变/药物疗法糖尿病血管病变/病理学糖尿病血管病变/病理生理学糖尿病肾病/药物疗法糖尿病肾病/病理学糖尿病肾病/病理生理学内皮血管/病理学红细胞/药物作用红细胞/酶学心率/药物作用吲哚类/治疗应用肾功能试验肌平滑血管/病理学心肌/病理学丙酸苯酯类/治疗应用嘧啶类/治疗应用大鼠 Wistar 受体内皮素A 受体内皮缩血管肽/拮抗剂和抑制剂动物男(雄)性大鼠

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Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第6期33卷 1506-1511页

作者： O'Driscoll, G Green, D Maiorana, A Stanton, K Colreavy, F Taylor, R Univ Western Australia Dept Human Movement Nedlands WA 6907 Australia Univ Western Australia Dept Med Nedlands WA 6009 Australia Royal Perth Hosp Dept Cardiol Endocrinol Nedlands WA Australia Royal Perth Hosp Dept Diabet Nedlands WA Australia

OBJECTIVES The aim of this study was to assess the effect. of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes. BACKGROUND Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilatian. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type ii diabetic subjects using a. double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N-G-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the Spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes. (C) 1999 by the American College of Cardiology.

关键词：乙酰胆碱血管紧张素转换酶抑制药/投药和剂量血管紧张素转换酶抑制药/副作用血流速度/药物作用血流速度/生理学糖尿病 2型/药物疗法糖尿病 2型/病理生理学糖尿病血管病变/药物疗法糖尿病血管病变/病理生理学剂量效应关系药物双盲法用药计划表依那普利/投药和剂量依那普利/副作用内皮血管/药物作用内皮血管/病理生理学前臂/血液供给硝普钠 ωN-甲基精氨酸老年人人类中年人

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Morphological changes in the sciatic nerve of diabetic rats treated with low molecular weight heparin OP 2123/parnaparin

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ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C 2002年第4期31卷 193-197页

作者： Artico, M Massa, R Cavallotti, D Franchitto, S Cavallotti, C Univ Roma La Sapienza Chair Human Anat Rome Italy Univ Roma Tor Vergata Dept Neurosci Rome Italy S Spirito Hosp Div Neurophysiopathol Rome Italy

This study points out the early alterations that affect the sciatic nerve of rats with experimentally induced diabetes. It emphasizes the advantages deriving from treatment with low molecular weight heparin (LMWH) OP 2123/parnaparin and correlates these findings with observations emerging from a review of the relevant literature. In fact, the number and diameter of the capillaries within the sciatic nerve of diabetic rats appear to be increased consistent with a microangiopathy (the main characteristic of which is the fragility of new vessels), that is related to the evolution of diabetes in humans and animals. Our results suggest a possible therapeutic role for OP 2123/parnaparin in both diabetic neuropathy and microangiopathy, frequent complications of diabetes.

关键词：抗凝药/药理学抗凝药/治疗应用糖尿病实验性/药物疗法糖尿病实验性/病理学糖尿病 1型/并发症糖尿病 1型/药物疗法糖尿病 1型/病理学糖尿病血管病变/药物疗法糖尿病血管病变/病理学糖尿病血管病变/预防和控制糖尿病神经病变/药物疗法糖尿病神经病变/病理学糖尿病神经病变/预防和控制肝素低分子量/药理学肝素低分子量/治疗应用图像处理计算机辅助微循环/药物作用微循环/病理学大鼠 Wistar 坐骨神经/血液供给坐骨神经/药物作用坐骨神经/病理学动物男(雄)性大鼠

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Differential effects of antihypertensive agents on electrocardiographic voltage: Results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial

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AMERICAN HEART JOURNAL 2003年第6期145卷 993-998页

作者： Havranek, EP Esler, A Estacio, RO Mehler, PS Schrier, RW Univ Colorado Hlth Sci Ctr Div Cardiol Denver CO 80262 USA Univ Colorado Hlth Sci Ctr Div Gen Internal Med Denver CO 80262 USA Univ Colorado Hlth Sci Ctr Div Renal Dis & Hypertens Denver CO 80262 USA Dept Med Denver CO USA Colorado Prevent Ctr Denver CO USA Denver Hlth & Hosp Denver CO USA

Background Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events. Methods We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis. Results In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P = .002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events. Conclusions In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all,. of the effect of enalapril in this study.

关键词：抗高血压药/治疗应用血压/药物作用血压/生理学钙通道阻滞药糖尿病 2型/并发症糖尿病 2型/病理生理学糖尿病血管病变/药物疗法糖尿病血管病变/病理生理学双盲法心电描记术依那普利/治疗应用高血压/药物疗法高血压/病理生理学肥大左心室/药物疗法肥大左心室/病理生理学尼索地平/治疗应用比例危险度模型前瞻性研究成年人老年人女(雌)性人类男(雄)性中年人

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Management of coronary artery disease: Therapeutic options in patients with diabetes

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期36卷 355-365页

作者： Hammoud, T Tanguay, JF Bourassa, MG Montreal Heart Inst Dept Med Montreal PQ H1T 1C8 Canada

OBJECTIVES The aim of this review is to discuss the particularities of coronary artery disease (CAD), the effect of intensive medical management and the outcome of percutaneous and surgical revascularization in patients with diabetes mellitus (DM). BACKGROUND CAD represents the leading cause of death in patients with DM. Numerous clinical, biological and angiographic risk factors have been shown to be associated with CAD in diabetic patients. METHODS Metabolic abnormalities in patients with DM including insulin resistance, hyperglycemia and dyslipidemia are briefly discussed. Then the potential roles of medical management and of percutaneous and surgical coronary revascularization are more extensively reviewed. RESULTS More vigorous control of hyperglycemia, hyperlipidemia, hypertension and other risk factors may be of crucial importance for risk reduction. Despite remarkable progress in recent years, the choice of a coronary revascularization strategy remains a challenge in these patients. Diabetic patients with CAD are predisposed to higher cardiovascular events after balloon angioplasty. Whether stenting and new antiplatelet drugs improve the results of percutaneous revascularization in this population needs further evaluation. The superiority of the surgical approach is also not definitely established. Therefore, many aspects of coronary revascularization are still unclear in these patients. CONCLUSIONS The results of ongoing randomized trials comparing multiple coronary stents to bypass surgery will likely provide some answers to our questions and additional randomized trials evaluating intensive diabetic control with or without coronary revascularization are needed to determine the best therapeutic approach in these patients. (C) 2000 by the American College of Cardiology.

关键词：血管成形术气囊冠状动脉血管紧张素转换酶抑制药/治疗应用抗体单克隆/治疗应用抗凝药/治疗应用糖尿病血管病变/药物疗法糖尿病血管病变/代谢糖尿病血管病变/病理生理学糖尿病血管病变/治疗内皮血管/病理生理学高血糖症/病理生理学高脂血症/病理生理学免疫球蛋白Fab片段/治疗应用胰岛素抗药性血小板聚集抑制剂/治疗应用血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂复发危险因素血栓溶解疗法治疗结果人类

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Regulation of VEGF in diabetic patients with critical limb ischemia

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ANNALS OF VASCULAR SURGERY 2001年第3期15卷 388-392页

作者： Hochberg, I Hoffman, A Levy, AP Technion Israel Inst Technol Fac Med IL-31096 Haifa Israel Rambam Med Ctr Dept Vasc Surg Haifa Israel

Diabetic patients are at a 10- to 20-fold increased risk for the development of critical limb ischemia. Vascular endothelial growth factor (VEGF) is critical for the development of collateral blood vessels, which can effectively bypass peripheral arterial occlusions. We therefore set out to determine if the regulation of VEGF in patients with peripheral vascular disease differs in diabetic and nondiabetic patients. Diabetic and nondiabetic patients with peripheral vascular disease were divided into those with or without critical limb ischemia as defined by clinical criteria (rest pain, nonhealing ulcer), Monocytes from peripheral blood were isolated from all patients and the hypoxic induction of VEGF was determined in vitro. In patients without diabetes, we found that there was no significant difference in the hypoxic induction of VEGF between patients with or without critical limb ischemia. However, in diabetic patients we found that patients with critical limb ischemia produced significantly more VEGF than patients without critical limb ischemia (6.3 +/- 1.3 vs. 2.1 +/- 0.3, p < 0.015). We conclude that diabetic patients with critical limb ischemia do not have an impairment in the ability to produce VEGF with hypoxia. Contrary to current dogma, treatment paradigms directed at increasing VEGF production in the diabetic patient with critical limb ischemia might not be beneficial.

关键词：危重病糖尿病血管病变/并发症糖尿病血管病变/药物疗法内皮生长因子/治疗应用缺血/药物疗法缺血/病因学腿/血液供给淋巴因子/治疗应用蛋白质亚型/治疗应用血管内皮生长因子A 血管内皮生长因子类老年人人类中年人

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硫辛酸联合丹参治疗糖尿病下肢血管病变54例

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陕西医学杂志 2016年第11期45卷 1548-1550页

作者：屈勇张燕平西电集团医院消化内分泌科西安710077 西安市莲湖区桃园社区卫生服务中心

目的:探讨硫辛酸与丹参治疗糖尿病下肢血管病变的临床疗效。方法:选择2型糖尿病合并下肢血管病变患者103例,根据不同药物治疗分为研究组54例和对照组49例。对照组均予糖尿病宣教、饮食控制、丹参等常规治疗,研究组在此基础上予联合硫辛... 详细信息

目的:探讨硫辛酸与丹参治疗糖尿病下肢血管病变的临床疗效。方法:选择2型糖尿病合并下肢血管病变患者103例,根据不同药物治疗分为研究组54例和对照组49例。对照组均予糖尿病宣教、饮食控制、丹参等常规治疗,研究组在此基础上予联合硫辛酸治疗,治疗21d为一个疗程。比较两组治疗前后WIQ量表评分、症状评分、足背动脉血流量、ABI、患肢血流动力学指标。结果:治疗前,两组WIQ量表评分、症状评分、足背动脉血流量、ABI、患肢血管内径、平均血流速度、血流峰值等血流动力学指标差异无统计学意义(P>0.05);治疗后,两组WIQ量表评分升高,症状评分降低,足背动脉血流量、ABI及血流动力学指标均增加,组内与组间差异均有统计学意义。结论:硫辛酸联合丹参治疗糖尿病下肢血管病变可显著改善患者行走功能、临床症状及血流动力学指标,增加肢体血流量,收到较好疗效。

关键词：糖尿病血管病变/药物疗法硫辛酸/治疗应用丹参/治疗应用疗效比较研究

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糖尿病微血管并发症的发病机制及药物治疗的研究进展

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医学临床研究 2022年第1期39卷 104-107页

作者：彭娟张静宝鸡高新医院内分泌科陕西宝鸡721000

糖尿病、高血压和恶性肿瘤严重威胁着人类的健康和生存状态[1]。随着不良饮食、生活习惯和人口老龄化的加剧,糖尿病及其并发症的发病率均有升高的趋势。糖尿病及其并发症的发病原因有多方面,可能与饮食、生活习惯、遗传、环境等方面有关... 详细信息

糖尿病、高血压和恶性肿瘤严重威胁着人类的健康和生存状态[1]。随着不良饮食、生活习惯和人口老龄化的加剧,糖尿病及其并发症的发病率均有升高的趋势。糖尿病及其并发症的发病原因有多方面,可能与饮食、生活习惯、遗传、环境等方面有关,但其确切的发病机制尚不明确[2]。目前,临床对糖尿病及其并发症尚无特效的治疗手段,多以降糖和改善胰岛素抵抗为主。糖尿病并发症包括糖尿病大血管并发症和糖尿病微血管并发症。

关键词：糖尿病血管病变/病因学糖尿病血管病变/药物疗法综述文献

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