Environmental factors, obesity and diabetes: Long-term study launched

Asian phenotype to be explored

Three Singapore biomedical institutions have launched a major, long-term study of pregnant mothers and their fetuses as well as infant children to determine just how profoundly environmental factors early in life influence the onset of diseases such as obesity and diabetes in later years.

The new research program, inspired by research evidence showing that the environment in which a baby is conceived, born and grows up determines the child's growth and development, will involve researchers based at the KK Women's and Children's Hospital (KKH), the National University Hospital (NUH) and the Singapore Institute for Clinical Sciences (SICS), which is part of A*STAR (Agency for Science, Technology and Research).

The lead investigator, Chong Yap Seng, M.D., of the National University Health System (NUHS), is working with a team of Singaporean and international researchers and is recruiting a total of 1,200 expectant mothers for the study, which initially will track children from fetal development to 3 years of age, and subsequently, if further funding is secured, as they grow up to become adults.

Attempts at modifying lifestyles to prevent or reduce diabetes, obesity and cardiovascular disease have had a limited impact thus far, Dr. Chong noted. Hence, the importance of a major initiative to study how fetuses respond to their environment during development.

"Present strategies for the management of obesity and diabetes are focused on the prevention of secondary complications rather than primary disease," he said.

"While there is little doubt about the benefits of exercise and healthy diets in improving overall health, it is evident that additional approaches must be explored to improve the long term effectiveness of interventions," added Dr. Chong, Associate Professor in the Department of Obstetrics and Gynecology, NUS Yong Loo Lin School of Medicine, and a Senior Consultant with the Department of Obstetrics and Gynecology, NUH.

Termed the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, this research effort is the centerpiece of the "Developmental Origins: Singapore" (DevOS) programme that was awarded the S$25m Translational and Clinical Research Flagship Programme Grant by the National Research Foundation in September 2008.

"There is increasing evidence that a baby's environment from conception to birth determines its childhood development and lifelong health and that factors in early development are major causes of metabolic diseases such as obesity and type 2 diabetes mellitus," said Sir Peter Gluckman, M.D., DevOS Executive Board Member, and Programme Director of SICS' Growth, Development and Metabolism Programme.

Dr. Gluckman, who has a strong interest in how nutrition in the womb affects a baby's health for the rest of its life, advises the World Health Organization, U.S. Agency for International Development and the World Bank on public health measures to improve the outcomes of pregnancy.

Knowledge gained from the study will be of immense importance to Singapore, said Associate Professor Kenneth Kwek, M.D., Co-Principal Investigator, GUSTO, DevOS.

"With the participation of Singaporean mothers-to-be recruited from the maternity units of the KKH and NUH, the research team hopes to discover effective prevention and early intervention strategies, which may be in the form of simple lifestyles, nutritional intervention or preventive drugs to reduce the burden of metabolic diseases," added Dr. Kwek, who is also Chairman, Medical Board and Head, Department of Maternal Fetal Medicine, KKH.

"As the GUSTO birth cohort is the first life course longitudinal follow-up study of babies from early pregnancy to childhood in Singapore, the study will provide valuable information on early fetal influences, genetic, and childhood environmental predictors of development and childhood health," added Saw Seang Mei, M.D., Co-Principal Investigator, GUSTO, DevOS.

"Important findings from our study will guide national public policy and improve the health of the population." Associate Professor Saw is also Vice-Dean (Research, Pre-Clinical), NUHS Research Office and Associate Professor, Department of Epidemiology and Public Health, NUS Yong Loo Lin School of Medicine.

And with the increased prevalence of obesity and diabetes in Singapore, there is a need to study the "Asian Phenotype" as much information about these diseases originates from studies conducted in the west. Research, however, indicates that Asians seem more prone to metabolic diseases at lower body mass index. Also, different ethnic groups seem to be at different risk levels, Dr. Chong said.

"The development of this research is timely as these diseases are rapidly increasing in prevalence throughout the world, especially in Asia," added Dr. Chong. "While much research in this area has been conducted in Caucasian populations, data has suggested that aspects of the diagnosis, prevention and treatment of metabolic diseases could differ between Asians and Caucasians, and also differ between the various Asian ethnic groups.

"There is an urgent need to try and identify biomarkers, such as epigenetic changes, that indicate increased risk for metabolic diseases and use these to tailor interventions for individuals at risk."

The prevalence rate of type 2 diabetes mellitus in Singapore is one of the highest in the world and has increased dramatically over the past three decades, from 1.9% of adults in 1975 to 8.2% in 2004.

The prevalence of obesity is also rising in Singapore and increased from 5.1% of adults in 1992 to 6.9% in 2004 with almost double the prevalence of school children at over 12%.