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[ADA2012]解读TODAY研究最新结果与儿童糖尿病
——美国科罗拉多大学医学院Philip S.Zeitler教授访谈
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作者:P.S.Zeitler 2012/6/10 11:36:00    加入收藏
内容概要:Zeitler教授:该研究所传递的最重要的讯息就是,与成人相比,这些儿童的糖尿病发病的进展更快,血糖控制进一步恶化,通常单药治疗会使无法实现血糖控制更快地发生。

  Philip S. Zeitler   美国科罗拉多大学医学院儿科系教授
  <International Diabetes>: This is not a particularly optimistic study but what is the most important message from this study?
Prof. Zeitler:  The most important message from this study is that in these kids, they seem to have a form of diabetes which is more aggressive than you generally see in adults with a rapid deterioration of glycemic control and the loss of control on monotherapy much more quickly than we see in adults.

  《国际糖尿病》:TODAY研究的结果并不是非常令人乐观,您认为其带给我们的最重要的信息是什么?
  Zeitler教授:该研究所传递的最重要的讯息就是,与成人相比,这些儿童的糖尿病发病的进展更快,血糖控制进一步恶化,通常单药治疗会使无法实现血糖控制更快地发生。

  <International Diabetes>:  Do we have a reason why it progresses much more rapidly in children than adults?
  Prof. Zeitler:  I don’t think we have any real idea. There are a couple of possibilities. It may be that the appearance of diabetes at a younger age is a marker of a genetic background that is more aggressive. You can imagine that if you have a set of genes that make you prone to rapid beta cell loss then you might be the type of person who, in the right situation, presents early on. So it may be that we are seeing two aspects of some genetic background. The other possibility is that puberty plays a role here and that being obese during puberty is a particularly bad thing.

  《国际糖尿病》:与成人相比这些儿童的糖尿病进展更快的原因何在?
  Zeitler教授:目前我们还不知道其确切的原因。可能有以下几种可能性。有可能年轻即发生糖尿病提示存在病情进展快的遗传背景。你可以想象,如果你存在使β细胞丧失更快的基因,那么你将可能属于早期就会发生糖尿病的人。另一种可能性是青春期在其中发挥了重要的作用,而青春期肥胖则使情况更为糟糕。

  <International Diabetes>: You were comparing it to gestational diabetes. How is that so?
  Prof. Zeitler: What is interesting about these kids is that there appear to be two groups. One is a group that progresses very rapidly and requires relatively early initiation of insulin therapy. The other group, however, are the other half of kids who have long-term control of diabetes on their original therapy, even on metformin monotherapy. Even with what we knew by the end of the study that there was decreasing adherence to medication, they seemed to almost have a situation where their diabetes has either resolved or substantially improved. This reminds us a lot of gestational diabetes where you have women who are at risk for diabetes and they have the stress of pregnancy added to their underlying risk and they develop diabetes. Some of those women go on to have permanent diabetes, whereas in others the diabetes resolves although it is a marker of future risk for diabetes again. We think we may be seeing something like this. We have half the group who have permanent onset of their diabetes at puberty and another half of the group who have a transient pubertal diabetes which is probably a marker for future trouble.

  《国际糖尿病》:您曾将其比作妊娠期糖尿病?这是为什么呢?
  Zeitler教授:有趣的是研究中的儿童可以分为两组。一组病情进展非常快,需要尽早实施胰岛素治疗;而另一组采用最初的治疗方案(甚至是二甲双胍单药治疗)可在很长一段时间内控制住糖尿病。尽管我们在研究结束时发现其用药的依从性有所下降,但其糖尿病仍能有所缓解或改善。妊娠期糖尿病时妇女的糖尿病发病风险显著增加,而怀孕则进一步增加了上述发病风险,使其最终发生糖尿病。其中一部分会发生永久性的糖尿病,而另一部分的糖尿病则能够缓解,尽管其未来仍存在糖尿病的发病风险。我们认为我们所观察的现象与之相似。我们研究中有一半的儿童将发生青春期永久性糖尿病,而另一半则仅存在短暂的青春期糖尿病(这部分儿童未来仍具有较高的糖尿病发病风险)。

  <International Diabetes>: What are the main predictors then for these two groupings?
  Prof. Zeitler: The analysis is still early but what it looks like at this point is those children who you are able to get under truly good control with normal HbA1c after just a couple of months of metformin, are very likely to continue on and do well. On the other hand, interestingly, those children who get a non-diabetic range HbA1c after two months of metformin but not a normal A1C, appear to be at higher risk for progression. In addition, if you look longitudinally, those kids who do well have a very stable A1C for a long period of time, whereas the kids that go on to fail, actually have a gradually rising HbA1c and you can actually pick them out even before their A1C gets back into the diabetes range.

  《国际糖尿病》:两组的主要预测因素有哪些?
  Zeitler教授:目前的初步分析显示,那些应用二甲双胍治疗数月即能将HbA1c降至正常水平的儿童更易维持较好的血糖控制,而那些应用两个月二甲双胍后仍无法将HbA1c降至正常水平的儿童其糖尿病则存在较高的进展风险。此外,纵向来看的话,血糖控制较好的儿童的HbA1c能够在长时期内保持非常稳定的状态,血糖控制失败的儿童其HbA1c则将逐渐升高,甚至在其HbA1c恢复至糖尿病范围前你就可以将他们挑出来。

  <International Diabetes>:  So if they are still at the pre-diabetic range after two months of treatment, it is a good sign that they will continue to progress towards diabetes?
  Prof. Zeitler:  Yes. Their risk for going back up again is much higher than the kids who have true control after two months. Also, if you are seeing the A1C rise, then they are likely to go on to fail and suggests that intervention at much lower A1Cs may be necessary rather than waiting for a truly out-of-target A1C.

  《国际糖尿病》:因此,如果二甲双胍治疗后其HbA1c仍处于糖尿病前期的诊断范围内,是不是意味着他们将进展为糖尿病?
  Zeitler教授:是的。与治疗2个月后血糖控制良好的儿童相比,这些儿童血糖再次升高至原来水平的风险要高得多,更难有效控制HbA1c的升高,这提示我们亟需在其HbA1c仍处于较低水平时进行干预。
 

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