Precision medicine for diabetic Individuals: a joint Malaysia-UK Effort (PRIME) project

糖尿病患者的精准医疗：马来西亚-英国联合努力 (PRIME) 项目

• 批准号: MR/T018186/1
• 负责人: Chim Lang
• 金额: $ 24.52万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT018186%2F1
• 关键词: Precision; medicine; diabetic; Individuals; joint

Malaysia has the highest rate of diabetes in Asia and one of the highest in the world. Adding to this problem is the growing number of obese Malaysian children and adolescents who are now or will be affected by diabetes. The harmful effects of diabetes on the vasculature or blood vessels dominate the complications caused by diabetes. These vascular effects affect the heart (to cause heart attack, stroke and heart failure), feet (leading to amputations), eyes (to cause blindness) and kidneys (to cause kidney failure). This escalating diabetes pandemic with its cardiovascular complications has huge effects both for the affected individual and their society. Despite sugar-lowering diabetic drugs and control of other cardiovascular risk factors, people with diabetes continue to succumb to the cardiovascular-related diseases. While efforts are being made to combat this diabetic epidemic through public health measures, new strategies are clearly needed to address and prevent the cardiovascular complications of diabetes. In the UK, we have pioneered the concept of personalised medicine through the use of genetics to determine who will and will not respond to commonly used drugs in diabetes, as well as for heart protective drugs such as those that lower blood pressure and cholesterol. We have also made substantial inroads in the use of artificial intelligence to analyse digital pictures of patients' retinas to find features that reveal a patient's current disease status and is predictive of future risk of complications such as stroke and heart disease. However, the majority of these studies on how diabetes and the cardiovascular complications arise and how patients respond to medications are from white European ancestry populations despite the fact that diabetes in Europeans is very different to diabetes in Asians. There is therefore an urgent need for detailed research into the specific causes and cardiac consequences of diabetes in Asians including those in Malaysia in order to identify the processes that drive the onset of cardiovascular complications of diabetes that exist in Malaysian ethnicities and use this to understand how best to manage diabetes in Malaysia. In our proposed PRIME partnership, we propose to build upon the precision medicine expertise in Dundee that includes the on-going £7 million NIHR Global Health Research Unit on Global Diabetes Outcomes Research INdia-Scotland Partnership for Precision medicine in Diabetes - INSPIRED (https://inspired-nihr.com/) project that is exploring specific differences in combinations of genomic, retinal and clinical determinants of complications of diabetes and therapeutic response between Scottish and the South Indian population. The plan is to embed insights from the on-going INSPIRED program into the PRIME project that will add value to each project. Using the available precision medicine expertise in Dundee, we will facilitate knowledge transfer to Malaysia for initial establishment of a similar concept using the Malaysian government initiated The Malaysian Cohort (TMC) study, that is the biggest and most comprehensive population-based cohort study in Malaysia. The overarching objective of the PRIME project is to develop an international collaboration between Dundee and Malaysia that will establish the potential for translation of precision medicine to management of diabetes and its associated cardiovascular complications in Malaysia.

马来西亚是亚洲糖尿病发病率最高的国家，也是世界上糖尿病发病率最高的国家之一，越来越多的马来西亚肥胖儿童和青少年现在或将要受到糖尿病的影响。糖尿病对脉管系统的有害影响。这些血管效应影响心脏（导致心脏病发作、中风和心力衰竭）、足部（导致截肢）、眼睛（导致失明）和肾脏（导致肾衰竭）。这种不断升级的糖尿病流行病及其心血管并发症对受影响的个人及其社会产生了巨大影响，尽管有降糖糖尿病药物和其他心血管危险因素得到控制，但糖尿病患者仍在努力控制心血管相关疾病。为了通过公共卫生措施对抗这种糖尿病流行病，显然需要新的策略来解决和预防糖尿病的心血管并发症。在英国，我们率先提出了个性化医疗的概念，通过利用遗传学来确定谁会对糖尿病做出反应，哪些人不会做出反应。糖尿病常用药物，以及心脏保护药物，例如降低血压和胆固醇的药物，我们在使用人工智能分析患者视网膜的数字图像以寻找能够揭示患者当前疾病状态并具有预测性的特征方面也取得了重大进展。然而，尽管欧洲人的糖尿病与欧洲人的糖尿病有很大不同，但大多数关于糖尿病和心血管并发症如何产生以及患者对药物反应如何的研究都来自欧洲白人群体。亚洲人的糖尿病。因此，迫切需要对亚洲人（包括马来西亚人）糖尿病的具体原因和心脏后果进行详细研究，以确定驱动马来西亚人糖尿病心血管并发症发作的过程，并利用它来了解如何在我们提议的 PRIME 合作伙伴关系中，我们建议以邓迪的精准医疗专业知识为基础，其中包括正在进行的耗资 700 万英镑的 NIHR 全球健康研究单位全球糖尿病结果研究印度-苏格兰精准医疗合作伙伴关系。在糖尿病 - INSPIRED (https://inspired-nihr.com/) 项目正在探索苏格兰人和南印度人群之间糖尿病并发症和治疗反应的基因组、视网膜和临床决定因素组合的具体差异。将正在进行的 INSPIRED 计划的见解融入到 PRIME 项目中，利用邓迪现有的精准医学专业知识，我们将促进知识转移到马来西亚，以便利用马来西亚政府发起的马来西亚计划初步建立类似的概念。队列（TMC）研究，这是马来西亚最大、最全面的基于人群的队列研究。 PRIME 项目的总体目标是发展邓迪和马来西亚之间的国际合作，从而建立将精准医学转化为管理的潜力。马来西亚的糖尿病及其相关心血管并发症。

项目成果

Nicorandil-induced colovesical fistula in a patient with diverticular disease.

• DOI: 10.1002/ccr3.3888
• 发表时间: 2021-03
• 期刊: Clinical case reports
• 影响因子: 0.7
• 作者: Noyes JD;Mordi IR;Zeb Q;Lang CC
• 通讯作者: Lang CC

Prediction of Major Adverse Cardiovascular Events From Retinal, Clinical, and Genomic Data in Individuals With Type 2 Diabetes: A Population Cohort Study.

根据 2 型糖尿病患者的视网膜、临床和基因组数据预测主要不良心血管事件：一项群体队列研究。

• DOI: 10.2337/dc21-1124
• 发表时间: 2022
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Mordi IR

Glucose-Lowering and Metabolic Effects of SGLT2 Inhibitors.

SGLT2 抑制剂的降血糖和代谢作用。

• DOI: 10.1016/j.hfc.2022.03.004
• 发表时间: 2022
• 期刊: Heart failure clinics
• 影响因子: 3.4
• 作者: Mordi IR

Letter by Singh et al Regarding Article, "Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)".

Singh 等人关于文章“恩格列净对 2 型糖尿病或糖尿病前期和射血分数降低的心力衰竭 (SUGAR-DM-HF) 患者左心室容量的影响”的信函。

• DOI: 10.1161/circulationaha.120.053057
• 发表时间: 2021
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Singh JS

Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.

• DOI: 10.2337/dc20-2518
• 发表时间: 2021-07
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Mordi IR;Lumbers RT;Palmer CNA;Pearson ER;Sattar N;Holmes MV;Lang CC;HERMES Consortium
• 通讯作者: HERMES Consortium