MRC APBI STratification and Extreme Response Mechanism IN Diabetes - MASTERMIND

目前2型糖尿病治疗的临床指南建议，给予患者的治疗主要取决于治疗的费用，并假设所有患者对治疗的反应相似。这忽略了一个事实，即对于许多治疗方法，2型糖尿病患者之间的反应存在巨大差异。如果有可能了解患者对治疗反应不同的原因，那么就有可能选择对个体患者最有效的治疗方法，从而使特定治疗的益处最大化，风险最小化。目的和目的本研究的目的是建立一个科学框架，用于发展2型糖尿病的分层治疗；这是针对一个病人或一组病人的个体化治疗，目的是在正确的时间给正确的病人服用正确的药物。在Strand 1中，主要目的是确定2型糖尿病患者对二线和三线治疗的极端反应的生物学机制。其目的是准确地确定为什么某些患者对同一种药物的反应截然不同。我们将定义临床特征，这些特征与患者是否更有可能对药物产生反应有关，包括那些没有反应的患者是否只是那些没有服用药片的患者。我们还将定义与血糖快速恶化相关的特征。我们将确定如果一个人对一种药物没有反应，他们是否可能对其他药物没有反应，或者这个人是否对所有的糖尿病治疗都没有反应。我们将通过要求患者短暂停止药物治疗来确定患者的反应是否一致；对药物反应良好的人在停止药物治疗后血糖会迅速上升。最后，我们将建立一个资源，使未来的药物反应的遗传和非遗传标记开发。在Strand 2中，我们将开发在使用分层方法进入临床实践之前所需的关键信息。我们将开发一个模型，使我们能够预测病人对特定治疗的可能反应。然后，我们将在理论上找出在2型糖尿病中使用分层治疗的有效和成本效益。潜在的应用和好处给那些可能对药物有反应的病人用药，而不给那些不太可能有反应的病人用药，有巨大的潜在好处。这在改善患者的血糖控制从而减少并发症的风险，减少他们需要服用的药片数量（从而节省不必要的治疗费用）以及减少无效治疗的副作用风险方面将有相当大的好处。对于制药业来说，它将使其他治疗无效的患者能够有针对性地开发药物，并确定最有可能从新药开发中受益的患者亚群。此外，这种关于为什么患者对已经开发的药物反应良好的新认识将有助于未来修改治疗方法，以改善患者的预后。

ContextThe present clinical guidelines for the treatment of type 2 diabetes propose that treatment given to patients is primarily determined by the cost of the therapy and assumes that all patients respond similarly to treatment. This ignores the fact that for many therapies there is enormous variation in response between individuals with type 2 diabetes. If it was possible to understand the reasons why patients responded differently to therapy then it would be possible to choose the therapy most likely to be effective for an individual patient thus maximising the benefit and minimising the risk of a particular treatment.Aims and ObjectivesThe aim of this research is to develop a scientific framework which will be used to develop the stratification of treatment in Type 2 Diabetes; that is individualising treatment for a patient or subgroups of patients with the aim of giving the right drug to the right patient at the right time. In Strand 1, the main aim is to define the biological mechanisms involved in patients' extreme response to second and third line treatment in type 2 diabetes. The objectives are to define exactly why some patients respond very differently to the same drug. We will define the clinical characteristics which relate to whether patients are more or less likely to respond to a drug, including whether the patients who do not respond are just those that do not take their tablets. We will also define those characteristics related to rapid deterioration of the blood glucose. We will determine whether if a person does not respond to one type of drug they are likely to not respond to other drugs or whether that person simply does not respond to all diabetes treatment. We will determine how consistent someone's response is by asking patients to stop their drug treatment briefly; someone who is a consistent good responder to the drug will have a rapid in rise in blood sugar when the drug treatment is stopped. Finally, we will set up a resource to enable future genetic and non genetic markers of drug response to be developed. In Strand 2 we will develop critical information that is required before an approach using stratification can come into clinical practice. We will develop a model which allows us to predict a patient's likely response to a particular therapy. We will then work out in theory when it would be both effective and cost effective to use treatment stratification in type 2 diabetes. Potential applications and benefitsThere are enormous potential benefits to giving drugs to patients who are likely to respond to them and not to patients who are unlikely to respond. This would have considerable benefits in improving the patient's blood sugar control and hence reducing their risk of complications, cutting down on the number of tablets that they need to take (hence saving money on unnecessary therapy) and reducing the risk of side effects to therapies that were ineffective. For the pharmaceutical industry it would enable targeted drug development for patients where other therapy was ineffective and also to define patient subgroups that were most likely to benefit from new drug development. In addition this new understanding about why patients responded very well to drugs already developed would aid in the future modification of therapy to give improved patient outcome.