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Metabolic Disease Development

Launched in June 2009, this TCR programme aims to provide a scientific base to design prevention and intervention strategies to reduce the burden of chronic diseases such as diabetes and obesity.  Formally known as the Translational Clinical Research (TCR) Flagship Programme on Developmental Pathways to Metabolic Disease, it is more commonly known as “Developmental Origins:  Singapore”, or DevOS for short.  DevOS is a $25 million project funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC).

This is an area of particular interest for Singapore and the rest of Asia, where the sharply rising incidence of Type 2 diabetes mellitus and obesity is coinciding with rapid nutritional and socioeconomic transitions.  There are significant ethnic and individual differences in predisposition to these diseases, and thus one of the objectives of this programme is to examine the causal pathways and, particularly, the developmental factors that contribute to these differences.

The programme consists of two main sub-studies:

  • A birth cohort study named “GUSTO” (Growing Up in Singapore Towards Healthy Outcomes) which involves:
    • Phenotyping of pregnant women and their children
    • Epigenetic and genomic assessment of birth tissues
    • Development of epigenetic methodology
    • Additional cohorts:  Premature Cohort, IVF Cohort, Intra Uterine Growth Restriction (IUGR) Case Control Study

 

 

Measurements during home-visit
First MRI of week-old baby at NUH
Relaxed at GUSTO Launch

  • An adult metabolism study named “SAMS” (Singapore Adult Metabolism Study) which involves:
    • Physiological studies on mechanisms underlying insulin resistance and ethnic differences in metabolic disease risk
    • Testing of efficacy of interventions in adults

Metabolic rate readings under
canopy hood
Comfortable during DEXA
scan in NUH
An "ouch-free" skinfold measurement

This TCR programme will leverage on its own and non-TCR supported basic science to effect:

  • Development of biomarkers
  • Identification of therapeutic targets for intervention

towards improved clinical applications in risk prediction, prevention, diagnosis, pharmaceutical treatment and public health recommendations.

Epigenetics will be developed as the main platform technology, to study how pregnancy and early childhood conditions (development) influence the tendency of individuals to develop metabolic disease later on in life.

This study’s main aim is to find ways to prevent these debilitating chronic diseases rather than just treating them or preventing their complications.

The research programme involves:

  • Basic scientists (bench), technologists, and clinical researchers (bedside)
  • Multiple disciplines:  Molecular biology, clinical physiology, endocrinology, obstetrics, paediatrics, psychology, psychiatry, metabolic imaging, nutritional ecology, eye health, neurocognition, epidemiology and public health
  • Multiple institutions:  NUHS, A*STAR, KKH, SGH, HPB, MOH, Liggins Institute, NZ;  Universities in the UK, USA and Canada.

Just 6 months into the study at end-2009, the programme had already leveraged major commercial partnership funds to extend the study beyond its original scope.  The programme has secured multiple industrial collaborations, and negotiations are ongoing with other industrial players that have expressed interest in the biomarkers study and early cognitive development.

Principal Investigator:  A/Prof Chong Yap Seng, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health Systems.

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