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国际糖尿病 >>EASD年会
[EASD2008]微血管病变与遗传易感性——R. W Bilous教授采访
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专家访谈  来源:国际糖尿病 2008/9/12 15:22:00    加入收藏
内容概要:R. W Bilous教授在2008年EASD年会上接受《国际糖尿病》记者采访时指出:“一部分病程很短的2型糖尿病患者已经出现了糖尿病性视网膜病或者糖尿病肾病,另一些慢性患者则没有微血管并发症发生。这些与遗传易感性以及患者所接受的不同治疗方式都有关系。一些基因看起来是与进展到糖尿病肾病相关的。但从我们的研究中还不能得出任何确凿的结论...”

International Diabetes:     The first question I have for you today is some patients with a long duration of type 2 diabetes haven’t suffered from microvascular complications. However, some patients with a short duration have already suffered from diabetic retinopathy or diabetic nephropathy. Is this associated with different genetic susceptibility or different control of diabetes?

《国际糖尿病》:我的第一个问题是一部分慢性2型糖尿病的患者并没有微血管的并发症,但是一部分病程很短的病人已经出现了糖尿病性视网膜病或者糖尿病肾病。这些是与遗传易感性有关吗?或者与不同治疗方式有关?

Prof. R. W. Bilou:It’s probably a combination of the two I think. There seemed to be some genes which are   mapping to time to diabetic nephropathy. From our study we can’t really make any genetic conclusions. We don’t have genetic data on our patients. The duration of diabetes has to be less than 20 years for our type 2 patients. And on average of our baseline, it was usually about 8 or 9 years. So they are relatively short duration patients.

R. W. Bilou教授:我想它很可能与两者都有关。有一些基因看起来是与进展到糖尿病肾病相关的。但从我们的研究中还不能得出任何基因方面的结论。我们没有病人的基因资料。我们的2型糖尿病人的病程都是20年以内的。而我们的平均基线时间通常是8到9年,所以他们都是病程相对短的病人。

International Diabetes:     So do you think this perhaps might be something to follow up from a genetic angle another study perhaps …that someone might … do you think it might be a valuable study to look at?

《国际糖尿病》:因此您认为这可能是从基因角度进行随访的一个研究吗?…您认为这是一个值得关注的研究吗?

Prof. R. W. Bilou:Well there are numerous studies exploring genetic potential for nephropathy as well as retinopathy. But so far I think the gene effects that are being found although significant, have been relatively minor, and sometimes specific to different ethnic subgroups. Now in the Direct study, the vast majority of our patients were white European Caucasian patients. And as I’ve said, we don’t have any genetic information on these patients, so it’s going to be tough for us to add to that debate.

R. W. Bilou教授:是的,有很多研究探索了导致糖尿病肾病和视网膜病的潜在基因。但是到目前为止虽然遗传因素的作用虽然是有意义的,但影响仍然是比较轻微的,而且有时候只是针对不同的种族亚群。在Direct研究中,大部分患者都是来自欧洲的白种人。正如我说过的那样,我们没有病人的基因资料,所以我们很难在这方面下结论。

International Diabetes:     Sure. The next question is according to your study, are there any differences in the effects on albuminuria in response to ARBs in type 1 diabetes and type 2 diabetes?

《国际糖尿病》:下一个问题是根据您的研究,1型和2型糖尿病中白蛋白尿对ARB治疗的反应有什么不同吗?

Prof. R. W. Bilou:Ok. You must remember that all of these patients were normal on the albuminuric baseline, with a very low albuminuria excretion rate, so on average 5 micrograms per minute. So we were looking at the developments of new microalbuminuria in these patients. There were many more events in the type 2 patients than there were in the type 1 patients probably because blood pressure was higher in the type 2 patients. But we did not find any statistically significant difference in microalbuminuria developments on Candesartan in the type 1 and type 2 patients. Now the study is slightly complicated because nearly 400 patients were started on ACE-inhibitors during the course of the trial and these are open label drugs and more in the placebo group. So now in the process of exploring whether this may have influenced the results, at the moment all we’ve got is the headline data, we need to do much more exploratory analysis.

R. W. Bilou教授:你一定还记得所有这些病人起初在白蛋白尿方面是正常的,白蛋白尿排泄率很低,大约5mg/min。所以我们是在病人中观察新发生的微量白蛋白尿。在2型糖尿病患者中事件远多于1型糖尿病患者,可能原因是2型患者的血压更高。但是我们没有发现在使用坎地沙坦(Candesartan)的1型和2型患者中发现微量白蛋白尿的发展有任何统计学差别。但是现在这项研究中有一点复杂,因为在试验过程中有近四百名患者开始使用ACE抑制剂,ACE抑制剂是开放标签的药物而且在对照组中有更多的人服用了这种药。我们还在分析这一因素是否可能已经影响了结果,当前我们获得的是正在处理的数据,我们还要做更多探索性的分析。

International Diabetes:     And according to DIRECT Renal, besides the effects of BP lowering, what’s associated with the impacts of RAS blockade on diabetic nephropathy?

《国际糖尿病》:根据DIRECT Renal的结果,除了降低血压,还有什么是与RAS阻断对糖尿病肾病的作用有关的?

Prof. R. W. Bilou:Well, at the moment from our data as presented today we can’t say that Candesatan has a role for the primary prevention of microalbuminuria. But our patients have very low albuminuria baseline and many of them will never develop diabetic nephropathy. We know that maybe 20-40% only develop diabetic nephropathy. So we have probably selected out patients at low risk of nephropathy development because this was a retinopathy study, this was not a nephropathy study. So we need to do much more exploratory analysis for an understanding of our patients before we can really draw firm conclusions. But as I showed you in the presentation our data are quite consistent with the previously published data on primary prevention of microalbuminuria in type 1 and type 2 diabetes. So we are not showing anything different.

R. W. Bilou教授:根据我们现有的数据,就像今天汇报的那样,还不能说坎地沙坦(Candesatan)对微量白蛋白尿的一级预防是有用的。我们患者的基线白蛋白尿水平本来就很低,他们中的很多人根本就不会发生糖尿病肾病。我们知道可能只有20%~40%会发生糖尿病肾病。所以,我们可能只筛选了较低发生糖尿病肾病风险的病人,因为这是一项糖尿病视网膜病研究,而非糖尿病肾病研究。因此我们还需做更多的探索性研究才能得出肯定的结论。但是我刚才报告中展示的数据与以前发表的在1型和2型糖尿病中预防微量白蛋白尿的数据十分吻合,所以我们并没有展示任何不同的东西。

International Diabetes:     And as you mentioned that being a retinopathy study, what if we learn about the progression of retinopathy and do you feel like there is an adequate model for the progression of retinopathy at this time?

《国际糖尿病》:您提到这是一项针对视网膜病的研究。我们从中可以得到什么与视网膜病进展有关的信息呢?您认为这个模型在现阶段已经足够了吗?

Prof. R. W. Bilou: We use the gold standard method of assessing and grading retinopathy, the ETDRS scale. But as you heard from the discussion, it has its limitations, particularly when you are looking for regression. But we think we’ve shown conclusively in all three studies, that Candesatan is associated with less new retinopathy and in those with retinopathy you get more regression and less progression in type 1 and type 2 diabetes on Candesatan.

R. W. Bilou教授:我们用ETDRS标准做为对视网膜病进行评估和分级的金标准。但是正如你可能在刚才的讨论中听到的那样,它也有一些局限,特别是当你关注到好转的话。但是我们在三个研究中都可以得到确定的结论,即坎地沙坦(Candesatan)与新发视网膜病减少有关,而在已经患有视网膜病的1型和2型糖尿病患者身上你可以看到坎地沙坦(Candesatan)治疗导致更多的好转和更少的进展。

 

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