Anna Gloyn: Genetics and Diabetes
Predictions suggest that by 2030, 366 million people worldwide will be affected by diabetes, a disease which already uses 10% of the NHS budget. Continued breakthroughs in the area of genetics related to different types of diabetes enable better diagnosis and treatment for patients and identify novel pathways that can be targeted for therapeutic interventions.
Q: Do genes have a role to play in the risk of getting diabetes?
AG: Yes they do but there are many different types of diabetes and the amount that your genes contribute actually depends on the particular type of diabetes we are talking about. There are some very rare forms of diabetes and for these the genes have a major impact and then there are some common forms of diabetes, such as type 2, and for these it's a combination of your genes and the environment. If we take type 2 diabetes for instance, if you have a brother or a sister with type 2 diabetes then you are three times more likely to get diabetes than somebody in the general population. But the good news is that it's not all about your genes and we know you can reduce your chances of getting diabetes or delay its onset by exercising more and eating less.
Q: How much do we know about the genetics of diabetes?
AG: We know quite a lot now actually and we have made substantial progress over the last few years with some rare monogenic forms of diabetes which are due to a defect in just one gene. And more recently we have made significant headway with the more complicated type 2 diabetes where genes and environment pay a role; we now know that there are over 50 different genes that play a role. But this is just the tip of the iceberg because they only account for very small proportion (about 10%) of that genetic risk I was mentioning.
Q: How can this help us diagnose or treat patients?
AG: For these rare forms of diabetes we are now able to offer genetic testing that gives a definitive diagnosis to patients and this is really important because it can help the doctor decide how best to treat and manage that person's diabetes. There are also important implications for family members because with these rare forms of diabetes there is a 50% chance of passing the diabetes on to your child, of course here we can do genetic counselling and we monitor that person's risk. For the more common forms of diabetes we are only just starting to think about how we might be able to use this genetic information to tailor treatments and to think about predicting whether or not a person is more or less likely to get diabetes. This is very much an active area of research.
Q: What are the most important lines of research that have developed over the past five or ten years?
AG: I think one of the biggest breakthroughs has really come from work that Oxford itself contributed to, which were large scale genetic association studies; these have identified these 50 or so genes that are implicated in diabetes risk. What they have told us is that it is the insulin secreting cells that are most important and that defects in the insulin secreting machinery are what lead to diabetes. We also know that the number of these cells makes a significant impact on your risk for developing the disease.
Q: Why does your line of research matter, why should we put money into it?
AG: Diabetes isn't a very nice condition to have: it increases your risk of having a heart attack, it leads to blindness, and it also leads to kidney damage. We know that it takes over more than 10% of the NHS budget so it has significant implications for cost. We also know as we move forward that this is going to increase because it is predicted by 2030 that a staggering 366 million people worldwide will have diabetes; and of this over 95% will be type 2.
Q: How does your research fit into translational medicine within the department?
AG: It fits in very nicely actually because the ultimate goal of my work is to try and translate this genetic information into biological insights into how that insulin secretion machinery works. The hope is that if we uncover novel biological pathways we might be able to exploit these for developing new therapeutic interventions. But this isn't a simple process and it's going to require lots of different steps along the way. I am working very closely with colleagues here in Oxford firstly to try and work out what is happening at the level of this insulin secreting cell and secondly to study these genetic variants in the whole human being to see what the effects are on physiology.