MRC APBI STratification and Extreme Response Mechanism IN Diabetes - MASTERMIND

MRC APBI 糖尿病的分层和极端反应机制 - MASTERMIND

• 批准号: MR/K005707/1
• 负责人: Andrew Hattersley
• 金额: $ 348.32万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK005707%2F1
• 关键词: MRC; APBI; STratification; Extreme; Response

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.

目前治疗2型糖尿病的临床指南提出，对患者的治疗主要由治疗费用决定，并假设所有患者对治疗的反应相似。这忽略了这样一个事实，即对于许多治疗方法，2型糖尿病患者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单个患者最有效的治疗方法，从而使特定治疗的益处最大化和风险最小化。目的和目的本研究的目的是开发一个科学框架，用于制定2型糖尿病的治疗分层；即对患者或患者亚组进行个性化治疗，目的是在正确的时间给正确的患者正确的药物。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所涉及的生物学机制。其目的是明确为什么一些患者对同一种药物的反应非常不同。我们将定义与患者对药物有更多或更少反应相关的临床特征，包括没有反应的患者是否只是那些没有服用药片的患者。我们还将定义那些与血糖迅速恶化相关的特征。我们将确定如果一个人对一种药物没有反应，他们很可能对其他药物没有反应，或者这个人是否只是对所有糖尿病治疗没有反应。我们将通过要求患者短暂停止药物治疗来确定某人的反应有多一致；对药物始终如一有良好反应的人在药物治疗停止时血糖将迅速上升。最后，我们将建立一个资源，使未来的遗传和非遗传的药物反应标记得以开发。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。我们将开发一种模型，使我们能够预测患者对特定疗法的可能反应。然后，我们将在理论上研究出在2型糖尿病中使用分层治疗既有效又成本效益高的情况。潜在的应用和好处给可能对药物有反应的患者，而不是给不太可能有反应的患者，有巨大的潜在好处。这将在改善患者的血糖控制方面有相当大的好处，从而降低他们出现并发症的风险，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)，并减少无效治疗的副作用风险。对于制药业来说，它将为其他疗法无效的患者进行有针对性的药物开发，并确定最有可能从新药开发中受益的患者亚群。此外，对为什么患者对已经开发的药物反应良好的新理解将有助于未来改进治疗方法，以改善患者结果。

项目成果

Time trends and geographical variation in prescribing of drugs for diabetes in England from 1998 to 2017.

• DOI: 10.1111/dom.13346
• 发表时间: 2018-09
• 期刊: Diabetes, obesity & metabolism
• 作者: Curtis HJ;Dennis JM;Shields BM;Walker AJ;Bacon S;Hattersley AT;Jones AG;Goldacre B
• 通讯作者: Goldacre B

Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy.

• DOI: 10.2337/dc17-1827
• 发表时间: 2018-04
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Dennis JM;Shields BM;Hill AV;Knight BA;McDonald TJ;Rodgers LR;Weedon MN;Henley WE;Sattar N;Holman RR;Pearson ER;Hattersley AT;Jones AG;MASTERMIND Consortium
• 通讯作者: MASTERMIND Consortium

Clusters provide a better holistic view of type 2 diabetes than simple clinical features - Authors' reply.

与简单的临床特征相比，聚类可以更好地全面了解 2 型糖尿病 - 作者的回复。

• DOI: 10.1016/s2213-8587(19)30250-5
• 发表时间: 2019
• 期刊: The lancet. Diabetes & endocrinology
• 作者: Dennis JM

Crossover studies can help the individualisation of care in type 2 diabetes: the MASTERMIND approach

交叉研究有助于 2 型糖尿病的个体化护理：MASTERMIND 方法

• DOI: 10.1002/pdi.2015
• 发表时间: 2016
• 期刊: Practical Diabetes
• 影响因子: 0.6
• 作者: Angwin C

Dirichlet process mixture models to impute missing predictor data in counterfactual prediction models: an application to predict optimal type 2 diabetes therapy.

• DOI: 10.1186/s12911-023-02400-3
• 发表时间: 2024-01-08
• 期刊: BMC medical informatics and decision making
• 影响因子: 3.5