Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus.
Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus.
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DOI：
10.1007/s00592-014-0708-6
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发表时间：
2015-08
影响因子：
3.8
通讯作者：
Beckman, Joshua A.
中科院分区：
文献类型：
--
作者：
Milian, Jessica;Goldfine, Allison B.;Zuflacht, Jonah P.;Parmer, Caitlin;Beckman, Joshua A.
血管疾病是1型糖尿病(T1 DM)发病率和死亡率的主要原因。我们先前证明，由于氧化应激增加，T1 DM患者的内皮功能受损，这是动脉粥样硬化的一种表现。胆红素已成为一种强大的内源性抗氧化剂，其浓度较高，心肌梗死和中风的发生率较低。我们测试了使用阿扎那韦增加内源性胆红素将改善T1 DM患者心脏代谢危险因素和血管功能的假设，以确定靶向胆红素是否可能是降低该人群心血管疾病风险的一种新的治疗方法。在这项单臂开放研究中，我们评估了15名T1 DM患者(平均年龄45±9岁)服用阿扎那韦4天后的血压、血脂和导管动脉功能。正如预期的那样，阿扎那韦显著提高了血清总胆红素水平(p<；0.0001)和血浆总抗氧化能力(p<；0.0001)。服用阿特拉那韦后，总胆固醇(p=0.04)、低密度脂蛋白(p=0.04)和平均动脉压(p=0.04)也降低了。在治疗前和治疗后，用高分辨率B超检测，血流介导的内皮依赖性(p=0.92)和硝酸甘油介导的内皮非依赖性(p=0.68)的血管扩张均无变化。在T1 DM患者中，使用阿扎那韦4天以上提高血清胆红素水平有利于降低低密度脂蛋白和血压，但与管道动脉内皮功能的改善无关。
Vascular disease is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have impaired endothelial function, a forme fruste of atherosclerosis, as a result of increased oxidative stress. Bilirubin has emerged as a potent endogenous antioxidant with higher concentrations associated with lower rates of myocardial infarction and stroke. We tested the hypothesis that increasing endogenous bilirubin using atazanavir would improve cardiometabolic risk factors and vascular function in patients with T1DM to determine whether targeting bilirubin may be a novel therapeutic approach to reduce cardiovascular disease risk in this population. In this single-arm, open-label study, we evaluated blood pressure, lipid profile, and conduit artery function in fifteen subjects (mean age 45 ± 9 years) with T1DM following a 4-day treatment with atazanavir. As anticipated, atazanavir significantly increased both serum total bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001). Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean arterial pressure (p = 0.04) were also observed following atazanavir treatment. No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured by high-resolution B-mode ultrasonography at baseline and post-treatment. Increasing serum bilirubin levels with atazanavir in subjects with T1DM over 4 days favorably reduces LDL and blood pressure but is not associated with improvements in endothelial function of conduit arteries.
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影响因子：
16.2
作者：
American Diabetes Association
通讯作者：
American Diabetes Association
DOI：
10.1161/atvbaha.110.211789
发表时间：
2011-02-01
影响因子：
8.7
作者：
Dekker, Douwe;Dorresteijn, Mirrin J.;Smits, Paul
通讯作者：
Smits, Paul
DOI：
10.1152/ajpheart.00899.2006
发表时间：
2007-06-01
影响因子：
4.8
作者：
Ingram, David G.;Newcomer, Sean C.;Laughlin, M. Harold
通讯作者：
Laughlin, M. Harold
影响因子：
37.8
作者：
Förstermann, U;Münzel, T
通讯作者：
Münzel, T
影响因子：
37.8
作者：
Beckman, JA;Goldfine, AB;Creager, MA
通讯作者：
Creager, MA