Obesity and non-communicable disease in Malaysia: an imaging study of 6000 adults in the Malaysian Cohort Study

Excess body fat is a major cause of diabetes, heart attacks and strokes, worldwide. Body-mass index (BMI; defined as weight in kilograms divided by height in meters squared) is the basis of the World Health Organisation's definition of overweight and obesity, with a BMI of between 25 and 30 kg/m2 classified as overweight, and over 30 kg/m2 as obese. However, there is increasing evidence that levels of body fat for a given BMI may vary between populations, raising questions regarding universally applied BMI-based guidelines for overweight and obesity. Although BMI is frequently used in Malaysia to assess excess body fat, there have been no large-scale imaging studies with direct measurements of body fat and its distribution which would allow us to understand better the relationship between body composition and disease outcomes in this population.

From 2006-2012, The Malaysia Cohort study - initiated by the Malaysian government - recruited 106,527 adults aged 35 years or over. Participants completed a lifestyle questionnaire, underwent physical measurements, provided a blood sample and are now being followed for health events. In 6000 of The Malaysia Cohort participants, we will conduct whole-body Dual-energy X-ray Absorptiometry (DXA) imaging (which provides data on body fat distribution in addition to body fat percentage) using protocols established by the UK Biobank (a large cohort study co-ordinated by the Nuffield Department of Population Health, University of Oxford). This imaging sub-study will significantly enhance this national biomedical resource.

Using DXA imaging, this study will reliably assess the relationship between conventional measures for estimating body composition (including BMI, waist circumference and waist-hip ratio) with the absolute regional fat masses derived from the DXA measurements in the Malaysian population. It will then assess the relationship between these measures and risk of diabetes and cardiovascular disease, to inform public health guidance on the appropriate measure of excess body fat in this population, the ideal 'normal' range of these measures, and whether guidance should vary for the different ethnic groups in Malaysia. DXA imaging will also significantly enhance the potential of The Malaysia Cohort to investigate the genetic and environmental determinants of obesity in Malaysia, and the biological pathways through which it causes diabetes and cardiovascular disease.

Not all people who are overweight or obese suffer adverse consequence from their excess weight, in part due to differences in fat distribution. Indeed, as recently reported from The Malaysia Cohort, the prevalence of obesity (based on BMI) and type 2 diabetes is very divergent between the major ethnic groups in Malaysia (Malay, Indian and Chinese) and this is only partly explained by BMI. Therefore, a better understanding of the between-ethnic group risk, based on tissue and organ-specific fat depots, will enable more precise targeting of limited resources to those who will gain the most benefit.

Although BMI is frequently used in Malaysia to assess excess body fat, there have been no large-scale imaging studies with direct measurements of lean mass and regional fat masses which would allow us to understand reliably the relationship between body composition and disease outcomes in this population. Such an imaging study would inform public health guidance on the appropriate measures of excess body fat in this population, the ideal 'normal' range of these measures, and whether guidance should vary for the different ethnic groups in Malaysia; understanding differences between ethnic groups is particularly important given the ethnic diversity of the Malaysian populations.

From 2006-2012, The Malaysian Cohort study - initiated by the Malaysian government - recruited 106,527 adults aged 35 years or over. Participants completed a lifestyle questionnaire, underwent physical measurements (including blood pressure, height, weight, hip and waist) and provided fasting blood and urine samples which were processed for long-term storage (half in -80C freezers and half in liquid nitrogen tanks). All participants are now being followed for health events. Baseline investigations included fasting blood glucose, fasting lipid profile, renal profile and full blood count, and re-surveys of a sample of the cohort are being conducted.

In 6000 of The Malaysian Cohort participants, we will conduct whole-body Dual-energy X-ray Absorptiometry (DXA) imaging (which provides data on body composition, details of fat distribution and body fat percentage) using protocols established by the UK Biobank (a large cohort study run by the Nuffield Department of Population Health, University of Oxford). This imaging sub-study will significantly enhance this national biomedical resource by focusing on factors directly relevant to the consequences of obesity along with opening up opportunities for international collaboration.

Obesity is a major cause of diabetes and cardiovascular disease with a substantial impact on the health and economic prosperity of populations in Malaysia and the UK. However, the scientific evidence to understand the true burden of obesity on these conditions, and the best measures of excess body fat in different populations (especially among different ethnic groups) remains unclear. Our hypothesis is there are intrinsic differences in body composition between ethnic groups, and that extrapolating findings from studies in European/North American populations may underestimate the real burden of diabetes and cardiovascular disease attributable to excess fat in Asian populations.

Academic beneficiaries: These data produced by this imaging study will be analysed by epidemiologists, statisticians and disease specialists at the Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI) and at the MRC Population Health Research Unit (part of the University of Oxford's Clinical Trial Service Unit & Epidemiological Studies Unit [CTSU]). The data would also be available for other researchers to use for their own investigations in accordance with our 'Data Access and Sharing Policy' (available at www.ctsu.ox.ac.uk), further benefitting researchers in the field.

Students beneficiaries: A key output from this project would include enhanced research collaboration between the UK and Malaysia, especially the training of young scientists and the development of research capacity in Malaysia. In particular, the Malaysian co-applicants' research group would gain expertise in the analysis and interpretation of DEXA data. Such knowledge transfer has the potential to lead to the establishment of new research programs at the Universiti Kebangsaan Malaysia (UKM) Medical Molecular Biology Institute. In parallel, the NDPH's DPhil program at the University of Oxford would provide opportunities to support the training of the next generation of Malaysian and UK epidemiologists with projects based on the rich data that would be available in the study (which would continue to be enhanced as larger numbers of health outcomes occur during prolonged follow-up).

General population: The ultimate aim of this project is to improve the health of the general public in Malaysia. The project aims to inform better health policy by providing reliable information on the impact of obesity on diabetes and cardiovascular disease, and better diagnostic and treatment options for the Malaysian population. It also aims to allow individuals to estimate more reliably their own risk of diabetes and cardiovascular disease, and raise public awareness of the steps individuals can take to reduce their risk of non-communicable disease.

Life sciences industry: This project will establish a shared resource and strengthen research capacity in the academic and life sciences industry in both Malaysia and the UK. It will do this through research and training of young scientists, and by enhancing The Malaysian Cohort Study. This cohort was initiated by the Malaysian government and will be a focal point of biomedical research and investment over the coming decade or more. The findings from this study will support translational advances in the management and prevention of obesity, diabetes and cardiovascular disease, some of which are likely to have commercial potential.