[PUDC2010]GLP-1类似物的潜在优势——Tina Vilsb?ll Lauritsen教授专访
Hidden Talents of GLP Analogues
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专家访谈 预防策略 作者未知 来源:未知 2010/5/12 9:47:00    点击数:8384    加入收藏
内容概要:GLP-1受体激动剂如Liraglutide(利拉鲁肽)治疗可降低患者收缩压和体重,改善beta细胞功能,降低不好的胆固醇及CVD相关标记物如CRP(C反应蛋白)。这可能是源于GLP-1对心脏的一些直接影响,可能通过在心脏上发现的GLP-1受体,内皮功能,或者可能是因为使用GLP-1治疗的人们在治疗的第一阶段钠排泄增加。然而,其确切机制目前尚不清楚。

    <International Diabetes>: Please summarize the latest developments for Glucagon like peptide -1   (GLP-1) in the clinical front.

      《国际糖尿病》: 请简要介绍胰高糖素样肽(GLP-1)在临床方面的最新进展。
    Dr Tina Lauristen: The problem in patients with type 2 diabetes is that they often suffer due to cardiovascular disease (CVD) and many of the current available treatments have in the past few years been a little worrying with respect to cardiovascular death.  Therefore it is really exciting this new class of treatment seems to have beneficial effects on the cardiovascular system. What we know is that there are GLP receptors spread throughout the body: in the heart, lung and central nervous system.  As of yet we are still unsure of the whole repertoire of their functions but in respect to the cardiovascular system is that when subjects are treated with GLP-1 receptor agonists as liraglutide for example results in a decrease in the systolic blood pressure, patients lose weight, they have improved beta cell function, decrease in bad cholesterol as well as markers associated with CVD such as CRPs (C-reactive protein).  If anything the wind does blow in the right direction towards beneficial effects on the cardiovascular system.

      Tina Lauristen教授: 2型糖尿病患者的问题在于他们经常合并有心血管疾病(CVD),而过去的几年已经发现目前采用的很多治疗可能增加心血管死亡危险性。而令人振奋的是这一类新的治疗看上去可使心血管系统获益。我们已经知道的是GLP受体遍布整个身体:在心脏,肺和中枢神经系统。虽然我们仍不能确定他们的全部功能,但在心血管系统,当受试者使用GLP-1受体激动剂如Liraglutide(利拉鲁肽)治疗可使收缩压下降,患者体重下降,它们具有改善beta细胞功能的作用,降低不好的胆固醇及CVD相关标记物如CRP(C反应蛋白)。它确实朝着正确的方向对心血管系统具有正性作用。
    <International Diabetes>: The exact mechanism as to how GLP-1 mediate their actions are still to be elucidated. Could you please highlight what you know or any research that is trying to understand this?

      《国际糖尿病》: 关于GLP-1如何发挥其作用的确切机制仍未阐明。请你介绍你所知道的或者关于此方面的研究?
    Dr Tina Lauristen: There are many things we don’t know exactly about the mechanisms because one of the surprising things with respect to systolic blood pressure is that the decrease in systolic pressure happens  very early after the initiation of treatment whilst body weight decreases very gradually up to half a year after treatment.  This seems to be attributed to some direct affect of GLP-1 on the heart perhaps maybe through the GLP-1 receptors found on the heart, endothelial function, or perhaps because we know that people treated with GLP-1 have an increased sodium secretion within the first period of the treatment. However, the exact mechanisms I do not know at this moment. 

      Dr Tina Lauristen教授: 确实关于机制方面有很多仍未阐明,关于收缩压令人惊讶的事情之一是在开始治疗后非常早期即出现收缩压下降,同时体重非常稳步的下降,直到治疗后半年。这可能是源于GLP-1对心脏的一些直接影响,可能通过在心脏上发现的GLP-1受体,内皮功能,或者可能是因为使用GLP-1治疗的人们在治疗的第一阶段钠排泄增加。然而,其确切机制目前我也不清楚。
    <International Diabetes>: The use of GLPs are associated with several side affects, which patients are unsuitable for GLP-1 treatment?  

      《国际糖尿病》: GLPs的使用与几种副作用有关,哪些患者不适于使用GLP-1治疗?
    Dr Tina Lauristen:  As GLP-1 based therapy is on the market now it is essentially added on to metformin. And the limitations of GLP-1 are pretty much the same as those seen with metformin. Patients with kidney failure should not be treated with GLP-1 because data from trials are not yet here. It is not yet approved as an add on therapy to insulin but I think this is just a matter of time. Right now I would say that at the moment these drugs should be given to patients with type 2 diabetes controlled by metformin. We don’t know who will benefit more from these drugs but I use GLP-1 therapy very often in many patients and they tolerate it fine. It is important to tell the patient that before the initiation of therapy that they have to be patient because as with metformin there are mild to moderate gastrointestinal side effects in some patients.  With the newer compounds this is seen less, this affect is mild moderate and transient so after 4- 6 weeks of treatment you are completely back to baseline.  

      Tina Lauristen教授: 基于市场目前GLP-1必须与二甲双胍联合治疗。并且,GLP-1的局限性与二甲双胍非常类似。由于目前尚没有试验数据,肾衰患者不应该使用GLP-1治疗。同样不受支持的是与胰岛素联合应用,但是我认为这仅仅是一个时间问题。现在我可以说在当前,这些药物应该给予使用二甲双胍控制的2型糖尿病患者。我们不知道谁可以从此类药物中获益更多,但是我在许多患者中非常普遍的使用GLP-1治疗,而且他们耐受良好。在开始治疗前告诉患者部分患者会出现像二甲双胍治疗一样的轻到中度的胃肠道副反应是非常重要的。随着新的药物的出现这些副反应减少了,这一作用是轻度缓和的而且是暂时的,所以4-6周的治疗后可以完全回复到基线水平。
 

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