It was all about our DNA at the EASD – by Emily Burns
Using genetics to prevent Type 1
TrialNet screens relatives of people with Type 1 diabetes to work out their personal risk of developing the condition. They have now screened over 175,000 people.
They can help people at risk of Type 1 diabetes to get involved with research, to help us learn more about how the condition develops and potentially test therapies that might slow it down. If we find treatments that work, a pathway like this could be used to prevent Type 1 from developing.
The pathway currently uses information about the person’s immune system to calculate their risk, but researchers in Exeter, including Diabetes UK fellow Dr Richard Oram, want to bring genetics into the mix.
Changes in several genes have been linked to a higher – or lower – risk of Type 1 diabetes. The research team has developed a ‘genetic risk score’: essentially a calculator that uses 30 genetic changes that have been linked to Type 1 diabetes to work out a person’s risk of developing the condition. The calculator helps to distinguish between Type 1 and Type 2 diabetes, to reduce the chances of someone getting misdiagnosed.
They’ve teamed up with TrialNet to see if the genetic risk score could be used to help predict the risk of Type 1 in their pathway. So far, they’ve tested it in 1,244 people enrolled on TrialNet – with promising results.
So if TrialNet is doing fine with their immune system tests, what’s the point? Everyone’s risk is different: two people could both be at risk, but at different levels. Combining the genetic risk score with current tests could start to add more detail to our grainy picture, helping to spread people across the ‘risk scale’.
Genome dark matter
Professor Jorge Ferrer, Imperial College London, delivered the prestigious Albert Renold Lecture, focusing on the potentials that genetic research holds.
“Our genome contains approximately 20,000 genes, which encode for the proteins needed for our cells to function. We now know that the human genome contains a much larger number of DNA stretches that act as switches that turn genes on or off in different cells,” explains Prof Ferrer.
He’s right: research often focuses on genes, essentially paragraphs of instructions on how to build proteins, the building blocks of our bodies. But those genes – all 20,000 of them – only represent about 2 per cent of our overall genetic code, or our DNA. What about the other 98 per cent? What does that DNA do, and if it goes wrong, what impact could it have in the context of diabetes?
There are forms of diabetes, such as MODY, that are caused by a single change (or mutation) in a gene. But those are relatively rare. Meanwhile, the role of genetics in Type 2 diabetes is more grey, as factors like ethnicity, age and our lifestyles all play a role.
So far, genetic studies in diabetes have focused on the genes, or the 2 per cent. The other 98 per cent contains switches that are able to turn particular genes on or off. Prof Ferrer suggests that Type 2 diabetes is linked to mutations within the switches, rather than the genes themselves.
While this makes the picture a bit more complex, it also opens up opportunities to develop new drugs. “This exposes networks that can be targeted to develop more effective therapies to halt this devastating disease.”
Making genetics the norm
Professor Ewan Pearson, Dundee University, was awarded the Minkowski Named Lecture, highlighting potentials of genetics once again.
Prof Pearson rightly argues that everyone with diabetes is different, so it’s likely that they’ll need to manage their condition in different ways – something we’re not currently geared up to do. He believes that genetics – and the variations our genes – could hold the key.
At the moment, scientists run tests to find mutations in genes. This is how we find people with the really rare forms of diabetes like MODY. But what about Type 2 diabetes? While much more complex, Prof Pearson predicts that one day you’ll be able to pull up your genetic information in your medical records, right alongside your weight and age.
If that became the case, doctors could use your genetics to make decisions about what treatments to give you. We’re already starting to see that some people respond differently to certain treatments, such as metformin, based on their genes.
If the researchers above are right, genetics could help to personalise the prediction, prevention and management of all forms of diabetes in the future.
And in case you didn’t catch it, there’s another EASD update on the research that hit the headlines.