Resolution of type II diabetes following RNY gastric bypass surgery: can gene expression profiling reveal the underlying dynamic mechanisms?

随着最近肥胖人数的增加，糖尿病患者的数量也在迅速增加，无论是在英国还是在世界范围内。尽管我们知道肥胖者患糖尿病的风险更大，但这种情况是如何发生的，为什么会发生，目前还知之甚少。我们也不明白为什么一些极度肥胖的人没有患上糖尿病。现在，通过某种形式的减肥手术来治疗严重肥胖症已经变得很普遍。令人惊讶的是，除了预期的减肥外，某些类型的手术有时还可以治愈糖尿病--甚至在减肥之前就可以了。这为研究糖尿病(除肥胖外)的病因提供了机会，并可能找到治疗或治愈糖尿病的新方法。我们将在手术前和手术后的不同时间从正在进行减肥手术的患者身上采集血液和组织样本。从这些样本中，我们将确定手术后哪些基因被开启或关闭，并通过比较手术治愈或未治愈的糖尿病患者与从未患过糖尿病的患者，我们将试图找到对糖尿病至关重要的基因。然后，我们将通过发现患者之间的基因差异，帮助解释这些基因是被大量还是仅仅少量地打开或关闭，来试图了解这些糖尿病相关基因是如何被控制的。为了验证我们的结果不是偶然的，我们将在其他减肥手术患者中寻找类似的结果。这项研究的结果可能有助于确定哪些患者将从减肥手术中受益最大。它还可能为如何开发治疗或治愈糖尿病的药物提供新的想法。

With recent increases in the number of people with obesity, the number of people with diabetes is also rapidly increasing, both in the UK and worldwide. Although we know that the obese are at greater risk of becoming diabetic, how and why this happens is poorly understood. We also do not understand why some extremely obese individuals do not become diabetic.It is now becoming common for severe obesity to be treated by some form of weight-loss surgery. Surprisingly, in addition to the expected weight loss, some types of surgery can sometimes also 'cure' diabetes - even before there has been any weight loss. This provides an opportunity to investigate the causes of diabetes (apart from obesity), and possibly to identify new ways of treating or curing it.We will take blood and tissue samples from patients who are having weight-loss surgery, both before surgery and at various times afterwards. From these samples, we will determine which genes are switched on or off following the surgery, and by comparing patients whose diabetes was or was not cured by the surgery with those who have never had diabetes, we will try to find genes that are important in diabetes. We will then try to understand how these diabetes-related genes are controlled, by finding genetic differences between patients that help to explain whether the genes were turned on or off by a lot or just a little. To check that our results are not due to chance, we will look for similar results in additional groups of weight-loss surgery patients.The results of this research may help to identify patients who will benefit most from weight-loss surgery. It may also provide new ideas about how to develop drugs that can treat or cure diabetes.