Salsalate: A Diabetes Treatment for Carbonyl, Oxidative & Nitrosative Stress

描述（由申请人提供）：项目摘要与非糖尿病患者相比，2型糖尿病患者患心血管疾病的风险增加。即使糖尿病患者从降血压、血脂控制和阿司匹林的使用中获得的益处比非糖尿病患者大，这种风险增加的情况仍然存在。由此可见，糖尿病患者中存在其他致动脉粥样硬化机制，而目前的心血管预防方法并未解决这些机制。改善这些“其他因素”可能会降低心血管疾病的风险。一个合理的“其他因素”是过度的氧化还原失衡，定义为活性氧、氮和碳分子的过量形成或不充分去除。糖尿病患者的氧化、羰基和亚硝化压力升高。这些过程与动脉粥样硬化的起始和传播有关。核因子-κ B（NF-κ B）是一种在炎症和氧化还原失衡的控制中起重要作用的基因。最近的实验室研究表明，双水杨酯-一种用于治疗关节炎的药物-可以阻断NF-κ B的激活。这一发现表明，双水杨酸可能是一种新的治疗方法的管理糖尿病。在2型糖尿病中使用双水杨酸靶向炎症（TINSAL T2 D）研究检查了双水杨酸作为治疗DM的新疗法范例的使用。其主要目的是测试是否抑制NF-κ B活性导致糖尿病患者血糖水平降低。其第二个结果是检查NF-kB的阻断是否导致与动脉粥样硬化有关的炎症和血管因子水平降低。目前的子研究旨在通过检查其对羰基、氧化和亚硝化应激的影响来了解双水杨酸治疗对糖尿病治疗的影响。这些因素被认为在DM的血管并发症中起重要作用。目前用于预防糖尿病并发症的药物治疗没有解决这些因素的改善。双水杨酸治疗降低氧化还原失衡可能在预防糖尿病血管并发症中发挥重要作用。 公共卫生相关性：项目叙述这项研究将测试双水杨酸，阿司匹林的一种形式，对糖尿病患者的使用。如果有效，这种治疗可以降低糖尿病患者经常发生的心脏病发作和中风的风险。

DESCRIPTION (provided by applicant): Project Abstract People with type 2 diabetes mellitus have an increased risk of developing cardiovascular disease compared to people without diabetes. This increased risk persists even though people with diabetes derive relatively greater benefit from blood pressure lowering, lipid control and aspirin use than do non-diabetic individuals. It follows from this that there are other atherogenic mechanisms, not addressed by current modalities of cardiovascular prevention, present in people with diabetes. Amelioration of these "other factors" could lead to lower cardiovascular disease risk. One plausible "other factor" is excessive redox imbalance, defined as the excess formation or insufficient removal of reactive oxygen, nitrogen and carbon molecules. People with diabetes have elevated oxidative, carbonyl and nitrosative stress. These processes are linked to the initiation and propagation of atherosclerosis. Nuclear factor kappa beta (NF-kB) is a gene which plays an important role in the control of inflammation and redox imbalance. Recent laboratory studies show that salsalate - a medication used for many years for the treatment of arthritic conditions - can block the activation of NF-kB. This finding suggests that salsalate may be a novel treatment approach for the management of DM. The Targeting Inflammation Using Salsalate in Type 2 Diabetes (TINSAL T2D) study examines the use of salsalate as a new paradigm of therapy for the treatment of DM. Its primary goal is to test whether the inhibition of NF- kB activity results in lower blood glucose levels in people with diabetes. Its seconday outcome is to examine whether blockade of NF-kB results in lower levels of inflammation and vascular factors implicated in atherogenesus. The present sub-study seeks to gain understanding of the impact of salsalate therapy for the treatment of DM by examining its effect on carbonyl, oxidative and nitrosative stress. These latter factors are believed to play an important role in the vascular complications of DM. Current medical therapy for the prevention of diabetic complications does not address the amelioration of these factors. Lowering redox imbalance with salsalate therapy may play an important role in the prevention of diabetic vascular complications. PUBLIC HEALTH RELEVANCE: Project Narrative This study will test the use of salsalate, a form of aspirin, for people with diabetes. If effective, this treatment could reduce the risk of heart attacks and strokes that frequently occur in people with diabetes.