August 2017 (Special Edition) | Issue 31
John Chambers: Tackling diabetes with large cohort studies

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By Nicole Lim, Senior Assistant Director, Communications & External Relations

Publish or perish goes the typical scientist’s career. Not one for the conventional, LKCMedicine’s newest recruit Professor of Cardiovascular Epidemiology John Chambers built his on a five-year effort during which he didn’t publish a single paper.

“The blood, sweat and tears that went into those five years transformed us into one of the most successful research groups at Imperial,” said Prof Chambers, who continues to hold an appointment at the College.
That effort was the London Life Sciences Prospective (LOLIPOP) study, a first-of-its-kind cohort study of South Asians living in London. He embarked on this study with his mentor, Imperial Professor of Clinical Cardiology Jaspal Kooner.

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The idea for the study came from the clinical need both of them faced while working at a district general hospital in north-west London. Prof Chambers, who was then a trainee cardiologist, found that the majority of his patients were South Asians and significantly younger than their European counterparts.

“I would treat patients who were as young as in their 20s, for heart attacks and diabetes,” said Prof Chambers. “This is an extraordinary clinical problem for these individuals, but also on a population scale.”

Prof Chambers’ interest in addressing population-wide problems had been sparked during the very first lecture he attended as an undergraduate at Oxford University. During that lecture, world-renowned epidemiologist Sir Richard Doll illustrated the impact of epidemiology on populations and future generations with a simple example. The example Sir Richard cited was the discovery by an Australian physician in 1941 of the link between Rubella and congenital malformations, which he worked out using just pen and paper.

“What's distinctive about epidemiology is that our focus is upon a problem, and we're perfectly happy to use any tool in the book to address it,” said Prof Chambers.

Finding the answer to why South Asians have a higher risk of cardiovascular and metabolic diseases started with a case-control study, comparing South Asians and Europeans who developed these diseases. Prof Chambers soon realised that there was a fundamental limitation to this work, akin to studying the aftermath of a car crash to determine what caused it.

“We were limited by reverse causality – was the broken headlight the cause of the crash or a consequence?” explained Prof Chambers.

This led to the LOLIPOP study. Between 2002 and 2008, the 20-strong research team recruited 40,000 participants. Prof Chambers devoted every spare moment to the study, including the extended public holiday over the Queen’s Golden Jubilee weekend. For him, it was four days to recruit 1,000 volunteers, starting at 8am and finishing at 2am the next day.

“I’d steal a couple of hours of kip on the office floor, before getting up again at 6am to freshen up and get ready,” he said.

Reaping rewards

Once the LOLIPOP cohort was recruited and data collected, the tides changed and funding poured in. From 2007 to 2010, the team was rewarded with over £10 million in grants, which paid for extensive state-of-the-art molecular phenotyping, and a string of publications in journals such as Nature, Nature Genetics and many others. Having collected extensive data from participants at the start of the study, the team, who continues to follow up with participants until now, can mine it for clues as to why some individuals went on to develop cardiovascular or metabolic diseases and others didn’t.

But LOLIPOP also presented a problem as it was a study of South Asians living in London. Could the change in environment play a role in their disease risk? The only way to answer that question was to do a similar study, but this time in South Asia.

Prof Chambers spent the next five years travelling the Indian subcontinent to recruit and equip local clinicians and researchers with the skills to conduct a similar population-based study, which will recruit 100,000 participants.

“Like LOLIPOP, this study will take 10 years to yield results,” said Prof Chambers, who is leading the development of a similar landmark study in Singapore, called Health for Life in Singapore (HELIOS), together with Imperial and the National Healthcare Group.

Introducing HELIOS

In collaboration with the National Healthcare Group and Imperial, LKCMedicine will lead a prospective cohort study, the Health for Life in Singapore (HELIOS) study. This population study aims to identify genetic and environmental factors that underpin th development of obesity, diabetes, cardiovascular and other complex diseases in Singapore through collection and mapping of phenotypic measurements, biological samples and long-term follow-up of participants. In time to come, the ultimate goal is to develop the HELIOS database into a powerful resource to aid the development of new approaches for prediction, prevention, earl detection and improved treatment of common chronic diseases in Singapore, thereby, improving the lives and health of generations of Singaporeans and Permanent Residents to come.

Some facts about HELIOS:

    1. It will eventually be the most comprehensive evaluation of the health of Singaporeans and Permanent Residents
    2. The study will carry out a comprehensive baseline evaluation, which includes assessment of lung function, body composition, bone density, blood vessel structure and function, eye health and a wide range of blood tests for each participant, and then follow their health status over the longer term
    3. Data will be securely stored for at least 20 years
    4. About 10,000 Singaporeans and Permanent Residents aged 30 to 84 will be recruited.
    5. Participants will receive a research health screening at no cost and a token of appreciation upon completion of the screening. If you are interested in participating in the study, please email for more information.

Prof Chambers added, “Coming to Singapore and LKCMedicine was a natural next step, locating me at the heart of the populations I hope to study. My work with HELIOS will help LKCMedicine deliver a unique cohort study for Singapore, while for me, it will strongly contribute to my ambition, before I die, to describe why these populations have higher risks of cardiovascular and metabolic disease.”

Adding intervention

But as a trained cardiologist, Prof Chambers does not just want to observe patients, he wants to intervene. With diabetes often a precursor of cardiovascular disease, Prof Chambers decided to focus his efforts in this field.

While obesity, smoking and lifestyle are known risk factors in the development of diabetes, they are not able to account for the three-fold increase in risk between Asians and Europeans, said Prof Chambers. Singapore, which has one of the world’s highest rates of diabetes and whose population is characterised by its multi-ethnic make-up, is the ideal location for this work.

Following his move to LKCMedicine, Prof Chambers is setting out on a five-year study to determine whether disturbances in DNA methylation, a regulator that switches genes on and off, and other molecular biomarkers can be used to better identify and treat people who are at high risk of developing type 2 diabetes.

To support the “Translating ‘omics into stratified approaches for prevention of type 2 diabetes” study, Prof Chambers received the National Medical Research Council’s most prestigious award, the Singapore Translational Research Investigator Award this year.

He is working with physicians from Tan Tock Seng Hospital to screen obese subjects, identify those with unhealthy metabolic molecular profiles and then randomise them into intervention or no intervention.

Because, Prof Chambers explained, “If we take a group of obese people, perhaps only one in 40 develops diabetes per year. But how can we pinpoint and treat the right person? That’s what I want to find out.”