Diabetes

Globally type 2 diabetes (T2D) affects over 500 million adults, including about 100 million in China, and the prevalence continues to rise steadily in most countries. Although the causes and consequences of diabetes have been extensively studied in Western populations, there is still limited data from China and other low- and middle-income countries, where the lifestyle, genetic susceptibility, and the detection and management of diabetes differ from those in Western populations. There is evidence that East Asians are more likely to develop insulin resistance-related T2D than Western populations for reasons that are still not properly understood. Better characterisation of the T2D disease phenotypes and associations with vascular and non-vascular complications in diverse populations may potentially improve risk prediction, identification of novel drug targets, and development of more personalised treatments for T2D patients.

Building on our previous research, we will continue to study genetic and non-genetic determinants and health consequences of T2D as well as novel biological mechanisms linking risk factors to T2D and its links to other disease outcomes.

Our current and planned work aims:

• to determine the likely cause-effect associations of lifestyle factors (e.g. alcohol consumption and physical activity) and traits (e.g. obesity) with T2D, using Mendelian randomisation approach;
• to examine the associations of T2D with a range of macro- and micro-vascular and other diseases (e.g. cancer, and infectious diseases) and assess how these associations are modified by other factors;
• to identify and categorise molecular clusters of T2D, using genetic loci representing likely disease mechanistic pathways (e.g. insulin resistance, β-cell dysfunction), and to characterise and refine such clusters using emerging omics data;
• to examine, compare and validate the associations of cluster-based genetic risk scores with T2D, risk factors, and major complications in the Chinese population and compared that with non-Chinese populations;
• to explore the roles of circulating protein and metabolite biomarkers (and other biomarkers) as mediators in the above associations.

To address these research questions, we will also use data from other biobanks (e.g. UK Biobank) and will seek close collaboration with academic and industry partners.