Approved Research

Investigating the interaction of adiposity and diabetes on molecular signatures and imaging phenotypes of cardiometabolic disease.

Lay summary

Diabetes mellitus (DM) is a disease where blood sugar levels become too high due to the body not making enough insulin or not responding properly to insulin. Currently over 4 million people in the UK have DM, with this number expected to rise in future.  People with DM often have obesity where they have large amounts of fat tissue, and these conditions combine to increase the risk of circulatory problems like stroke and heart attack; these reduce quality of life and are linked with increased risk of death. We have recently shown however, that people with DM of normal weight have abnormal distribution of body fat. We propose that the nature of the fat, and not just the volume of it in people with DM drives the increased risk of circulatory problems seen in people with DM.

Modern laboratory techniques, referred to collectively as 'omics, allow us to collect a snapshot of what is going on in a blood or tissue sample by measuring the levels of proteins or other molecules that our cells use to function. This information gives a complete picture of what happens in people with DM, which can be very useful in finding new treatment targets and diagnostic tests, but it generates very large lists of molecular differences that need to be confirmed and explored in follow-on studies.

Using blood and tissue samples collected from people with and without DM in our own research and other published research, we are creating lists of molecular differences in fat tissue and muscle from people with diabetes identified by these 'omic technologies. We plan to use UK Biobank to perform follow-on studies to check whether we find similar differences in people with DM. For molecules that we confirm, we will then use UK Biobank data to explore the link between levels of these molecules and signs of circulatory complications in people with diabetes. Overall, this information will allow us to identify: 1) promising molecular markers that can be measured in the blood to which people with diabetes have elevated risk of circulatory problems; and 2) potential new drug targets to slow the progression of circulatory complications in people with diabetes.