Approved Research

Using somatic mutation to understand adaptation to metabolic disease

Lay summary

Diabetes mellitus (DM) is a disease characterised by high blood sugar levels due to the reduced action or production of insulin. It is predicted that by 2050 between one in seven and one in eight adults will be living with diabetes. An even larger proportion of adults are now obese, with the majority of adults having a higher than ideal weight. Both DM and obesity increase the risk of many other health problems and so pose a major challenge for individuals, their families and society.

These risks can be ameliorated through healthy lifestyles, medications and other treatments. However, in spite of these, people with DM and/or obesity continue to experience much higher levels of problems like cardiovascular disease. This affects both their quality of life and life expectancy. We want to find new treatment approaches and think that studying how the body adapts DM and/or obesity will help this search.

Every cell in the body has its own set of instructions encoded in the DNA which makes our genes. At birth, it is usual for every cell to have very similar DNA. However, over time DNA in each cell experiences random damage that must be repaired. Occasionally the repair is not accurate, leading to a mutation in that cell - this is called somatic mutation. These mutations may give a cell an advantage over its neighbours, meaning that it can grow or survive more easily and so the mutation is passed on to more cells in that part of the body. Some of these mutations might give a particular advantage to cells in people with DM or obesity.

We have identified some potential somatic mutations that are more common in people DM or obesity. We will use UK Biobank to corroborate these and then see how they are associated with participants' wider health. This will help us to generate a list of somatic mutations that may allow cells to adapt to diabetes or obesity, which we can then take forward to complementary test tube studies.

This project will span across a 4 year timeline as part of a PhD project. We hope this information will allow us to improve the understanding of how the body adapts to diabetes and/or obesity, which could have major implications for designing new therapeutics.