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.

马来西亚的糖尿病发生率最高，是世界上最高的糖尿病之一。除此问题外，还有越来越多的肥胖的马来西亚儿童和青少年，他们现在或将受到糖尿病的影响。糖尿病对脉管系统或血管的有害作用占据了糖尿病引起的并发症。这些血管作用会影响心脏（导致心脏病发作，中风和心力衰竭），脚（导致截肢），眼睛（引起失明）和肾脏（导致肾衰竭）。这种不断升级的糖尿病及其心血管并发症对受影响的个体及其社会都产生了巨大影响。尽管降糖糖尿病药物并控制了其他心血管危险因素，但糖尿病患者仍会屈服于心血管相关疾病。尽管正在努力通过公共卫生措施来应对这种糖尿病流行，但显然需要采取新的策略来解决和防止糖尿病的心血管并发症。在英国，我们通过使用遗传学来确定谁将对糖尿病中常用药物以及受心脏保护的药物（例如降低血压和胆固醇的患者）的反应来启用个性化医学的概念。我们还在使用人工智能来分析患者视网膜的数字图片中发现了揭示患者当前疾病状况的特征，并预测了诸如中风和心脏病等并发症的未来风险。但是，尽管欧洲白人血统的糖尿病与亚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出现的研究以及患者对药物的反应是从欧洲白人血统群体中的大多数研究。因此，迫切需要详细研究亚洲人在内的糖尿病的特定原因和心脏后果，包括马来西亚的糖尿病，以确定推动马来西亚种族中存在的糖尿病心血管并发症发作的过程，并利用这是如何最好地管理马来西亚的糖尿病。在我们提出的主要合作伙伴关系中，我们建议建立邓迪的精确医学专业知识，其中包括持续的700万英镑的NIHR全球健康卫生研究部门全球糖尿病成果研究部门研究印度 - 苏格兰糖尿病精确医学的合作伙伴关系 - 受到启发 - 启发的（https：//inspired-nihr.com/），探索了整体的临床差异，并探索了一般的临床差异。糖尿病和南印度人口。该计划是将正在进行的灵感程序中的见解嵌入到主要项目中，以增加每个项目的价值。使用邓迪的可用精密医学专家，我们将开发将精密医学转化为糖尿病管理及其相关的马来西亚心血管并发症的潜力。

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

Precision Medicine and Adverse Drug Reactions Related to Cardiovascular Drugs.

• DOI: 10.3390/diseases9030055
• 发表时间: 2021-08-12
• 期刊: Diseases (Basel, Switzerland)
• 作者: Noyes JD;Mordi IR;Doney AS;Jamal R;Lang CC
• 通讯作者: Lang CC