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

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。使这一问题更加严重的是，越来越多的马来西亚肥胖儿童和青少年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影响在糖尿病引起的并发症中占主导地位。这些血管效应影响心脏（导致心脏病发作、中风和心力衰竭）、脚（导致截肢）、眼睛（导致失明）和肾脏（导致肾衰竭）。这种不断升级的糖尿病大流行及其心血管并发症对受影响的个人及其社会都产生了巨大影响。尽管降糖的糖尿病药物和其他心血管危险因素的控制，糖尿病患者继续死于心血管相关疾病。虽然正在努力通过公共卫生措施防治这种糖尿病流行病，但显然需要新的战略来处理和预防糖尿病的心血管并发症。在英国，我们开创了个性化医疗的概念，通过遗传学来确定谁会对糖尿病常用药物有反应，谁不会对糖尿病常用药物有反应，以及对心脏保护药物有反应，比如降低血压和胆固醇的药物。我们还在利用人工智能分析患者视网膜的数字照片方面取得了重大进展，以发现揭示患者当前疾病状况的特征，并预测中风和心脏病等并发症的未来风险。然而，这些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的研究大多来自欧洲白人血统人群，尽管欧洲人的糖尿病与亚洲人的糖尿病有很大不同。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种族中存在的糖尿病心血管并发症发病的过程，并利用这一点来了解如何最好地管理马来西亚的糖尿病。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学专业知识为基础，其中包括正在进行的700万英镑的NIHR全球糖尿病结果研究全球健康研究单位印度-苏格兰糖尿病精准医学合作伙伴关系- INSPIRED （https://inspired-nihr.com/）项目，该项目正在探索基因组、糖尿病并发症的视网膜和临床决定因素以及苏格兰和南印度人群之间的治疗反应。该计划是将正在进行的启发计划的见解嵌入到PRIME项目中，这将为每个项目增加价值。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，利用马来西亚政府发起的马来西亚队列（TMC）研究，初步建立类似的概念，这是马来西亚最大和最全面的基于人口的队列研究。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，这将为马来西亚糖尿病及其相关心血管并发症的精准医学管理奠定基础。

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.