Approved Research

Investigations into the association between transition of metabolic phenotype and the risk of chronic diseases, and the role of lifestyle and genetic factors

Lay summary

Maintaining metabolic health status will be highly valuable for disease prevention in later life. The public health impact of metabolic dysfunction is evident in the soaring rates of diabetes which increased the risk of multiple other diseases and secondary complications, such as cardiovascular disease (CVD). Accumulating evidence is gradually reaching a consensus that metabolic health is not a stable state, specifically among individuals with obesity. Determinants for metabolism changes remained to be explored further. High baseline body mass index (BMI) or waist circumference and long duration of obesity seemed contributing to metabolic deterioration according to previous work. CVD risk for obese group with metabolically healthy status was higher with longer duration of follow-up in limited studies, which backs up a transient nature of the metabolic phenotype. Unlike that ageing is an unavoidable process, the deterioration of metabolism could be prevented or reversed to some extent. In the real world, a large majority of young people had worse metabolism status, compared with the elderly. It is assumed that each individual had his/her "metabolism age", which was heterogeneous from the real age. Until now, longitudinal information on the transition of metabolic phenotype, as well as association between metabolism changes and the risk of other major health outcomes, such as vascular disease, chronic kidney disease, cancer and death, is surprisingly sparse. Accurate understanding of how metabolism changes and what genetic and lifestyle factors underlie these changes is essential for developing evidence-based strategies to prevent and postpone the occurrence of multiple diseases.

In this project, we aim to

-Describe how metabolic phenotype changes throughout human life course;

-Identify how lifestyle factors and genetics affect metabolic phenotype;

-Disentangle how the transition of metabolic status predicts incidence of important health outcomes, including type 2 diabetes, vascular diseases, cancers, and death among overall populations and stratified by obesity status.

We expect the project to run for 36 months. This research will provide strong evidence to reveal the change nature of metabolism and its determinants throughout a long duration, and underlie the related risk of important health outcomes. This project may increase our knowledge of disease mechanisms and help to identify new targets for disease prevention and treatment.