Fighting a Highly Prevalent Disease in Singapore on Multiple Fronts

In 2015, the Singapore Ministry of Health declared a “War on Diabetes.” However, the reality is that Singapore and the rest of the world had already been battling a growing diabetes epidemic for many years. The numbers are scary and the challenges multi-faceted. More than 11 per cent of Singaporeans aged 18 to 69 years have diabetes¹, almost 3 per cent higher than the global prevalence for people aged 18 and above^2,3. Another alarming fact is that Singapore has the highest rate of end-stage kidney failure due to diabetes in the world⁴. What’s more, diabetes as it manifests in Asian individuals is not the same illness that afflicts Westerners. It also tends to develop in Asians at lower BMI levels⁵ – emphasising the need to understand the biological basis for diabetes in Asia.

For these reasons, the Metabolic Diseases Summit Research Programme (SRP) brings together experts in fields ranging from molecular biology to the behavioural sciences to tackle diabetes treatment on two main fronts: 1) developing new therapies for metabolic disease, and 2) transforming the delivery of care to optimise outcomes for patients living with diabetes. Led by Professor Tai E Shyong of the Department of Medicine, the Metabolic Diseases SRP also aims to drive academic excellence and train new clinician scientists.

As Prof Tai sees it, “The healthcare system needs to be transformed from the current model, which is primarily designed to provide episodic care, to one that effectively engages patients and optimises outcomes for people with chronic disease.”

Developing novel therapies for metabolic diseases

The first aim of this programme will concentrate on developing therapies for three types of conditions that are inadequately addressed by currently available therapies (see Facts Box). Most of the research will focus on the early stages of the drug development process – identifying targets and validating their relevance to the biological mechanism of interest.

1. Glucose-lowering drugs
   – To treat insulin resistance (a precursor to type 2 diabetes). Such medications
   have the potential to control diabetes without causing hypoglycaemia as well
   as protect beta-cell function and lower CVD risk.
   – To treat non-alcoholic fatty liver disease
2. Nutritional therapies to prevent or treat type 2 diabetes
3. Therapies to prevent or slow the progress of diabetic kidney disease

Novel biological targets are already being identified through analysing patient cohorts for genetic, metabolomic and lipidomic (“omics”) changes associated with metabolic conditions such as insulin resistance. By validating these targets in human in-vitro models (e.g. human muscle cell cultures), the researchers can ensure the clinical relevance of the targets and subsequent lead compounds directed at them. Dr Liu Mei Hui, of the Department of Chemistry in the Faculty of Science (FoS), has already established several in-vitro models of human muscle, liver and breast. After this point, researchers in the programme will partner with pharmaceutical companies. The plan is for these companies to optimise the potential lead compounds and develop a drug that can be tested in first-in-man studies.

The drug development work will leverage on several unique shared capabilities at NUS Medicine. These include the Metabolic Phenotyping Core, which provides detailed characterisation of human metabolic parameters. The core is headed by clinician-scientist Khoo Chin Meng, an Assistant Professor in the Department of Medicine who studies different mechanisms of insulin resistance in Asian ethnic groups. Another platform is the Singapore Lipidomics Incubator (SLING), headed by Professor Markus Wenk of the Department of Biochemistry. The incubator can detect and analyse lipid profiles in health and disease. The omics research will generate an enormous amount of data, which the bioinformatics platform in the new Systems Biology Core can translate into useable information about new diabetes targets. Associate Professor Hyungwon Choi, of the Saw Swee Hock School of Public Health (SSHSPH), heads this core.

Transforming delivery of diabetes care

Even as the number of treatment options for diabetes continues to increase, the effectiveness of these therapies is still limited by how well patients adhere to them. The Metabolic Diseases SRP plans to apply behavioural science principles, including the use of incentives, apps, and more meaningful methods of communication, to improve provider and patient engagement. Associate Professors Rob van Dam and Joanne Yoong of SSHSPH, Associate Professor Leonard Lee of the School of Business, and Dr Yew Tong Wei of the Department of Medicine are spearheading these efforts.

Furthermore, as new diabetes prevention and care programmes are expected to be launched in the near future as part of the national war on diabetes, streamlining and coordinating these initiatives will be crucial. Here, applying healthcare data analytics can help to develop predictive algorithms to target care to patients for whom it will be most cost effective, and to improve care and outcomes for those patients who do not respond well to initial treatment.

Research in this area will be performed by Assistant Professor Tan Chuen Seng, Dr Kavita Venkataraman, and Dr Morning Feng (all from SSHSPH), as well as Assistant Professor Wee Hwee Lin (Department of Pharmacy, FoS) and Dr Ngiam Kee Yuan (NUHS Academic Informatics Office).

Currently, diabetes robs many people of years of life and health. By tackling key aspects of diabetes treatment using a variety of approaches, the Metabolic Diseases SRP aims to improve outcomes for people suffering from this common chronic disease.