ADA News: we’re finally talking about preventing Type 1 – by Emily Burns
We can’t prevent Type 1 diabetes from developing yet, but this hasn’t stopped scientists from trying. In our final ADA news update, we run through the latest prevention efforts – from finding people at risk, to testing treatments.
It’s in our DNA
Changes in our DNA can increase our risk of developing Type 1, and some of these changes can be passed through families. Professor Carla Greenbaum explained that having a family member with Type 1 can multiply your risk of developing the condition by roughly 15. *But* this doesn’t mean it’s a definite – the majority of people with Type 1 (eight out of 10 in fact) have no family history of the condition.
So this means that our genes can increase our risk of Type 1, but they don’t cause it on their own. This also means they’re a useful tool for spotting people who have a higher chance of developing Type 1 at some point in their lives.
Calling all babies
GPPAD scientists – a global network looking for ways to prevent Type 1 – are using genetics to find babies who have a higher chance of developing the condition. They’re recruiting pregnant mothers to their INGR1D study. INGR1D aims to check each new-born baby’s risk of developing Type 1 in their first week of life.
This genetic test can be performed at the same time as standard new-born testing, where a few drops of blood (often from the baby’s heel) are collected. The test will confirm if the baby is carrying high risk genes – around 1 in every 100 babies will have them. If they do, they have around a 10% chance of developing Type 1 during their life.
Most babies with high risk genes will never develop Type 1, but this trial gives new mothers two options. If their baby is at high risk, they can get advice on how to spot the symptoms of Type 1. Or, they could join the POInT trial – we cover this further down the page.
The pathway to Type 1
Genetic changes can be spotted incredibly early in life, but scientists now understand that this is just the first step on the pathway to Type 1 diabetes.
The immune system will begin to change in a small proportion of people who have a high genetic risk. Then, a small number of those people will develop what are called ‘autoantibodies’. These are molecules that tell us your immune system has mistakenly recognised something in your body as an enemy– the way it usually recognises viruses or bacteria.
There are different autoantibodies, and having one type of autoantibody doesn’t mean you’ll definitely develop Type 1. But again, a small proportion of people with one autoantibody will go on to have two, or three or four. At this stage in the pathway, your blood sugars will start to look iffy. The next stage is a diagnosis of Type 1.
TrialNet – another global network of scientists working to prevent Type 1 – is looking for ways to intervene in these stages, to stop people progressing to the next one, in the hope that they’ll never reach the point of a diagnosis.
They have screened over 200,000 people and have found 9,600 who have autoantibodies. 900 have taken part in prevention trials testing new treatments, but the TrialNet team is also following people through the different stages to learn more about why they progress.
The team has found that different factors can increase the chances of someone progressing. For example, younger people are likely to progress more quickly than older people. People with multiple autoantibodies (two or three, for example, instead of one) are also more likely to progress quickly and not just more types, but higher levels as well.
And then there are genes. Some genes appear to be protective: they’re more common in people who don’t have any autoantibodies. Other genes appear to increase risk: people carrying these genes are more likely to have autoantibodies.
Professor Polly Bingley has shown that around one fifth of people taking part in TrialNet progress from having one autoantibody to more than one. Age appeared to influence this the most (younger people were more likely to progress quickly), but they also found a small effect from genes. Those with a ‘low’ genetic risk were more likely to stick with one autoantibody than those with a ‘moderate’ or ‘high’ genetic risk.
Other studies have confirmed the same thing. One study in particular found that a change in a gene called CTLA4 appeared to increase the risk of progressing to multiple autoantibodies. Scientists are pretty excited about this because they already have a drug that interferes with CTLA4’s function, called Abatacept.
TrialNet has shown that Abatacept can protect insulin production in people newly diagnosed with Type 1. There’s another trial underway to see if Abatacept can prevent Type 1 – we’re expecting those results in a couple of years – and a third trial testing Abatacept in combination with a drug called Rituximab is starting this year. So watch this space.
A breakthrough moment
Abatacept isn’t the only drug we’re excited about. TrialNet scientists revealed that a drug called Teplizumab could delay the diagnosis of Type 1 diabetes by a median (a way of calculating the average) of two years.
It was a small trial involving just over 70 people at very high risk of developing Type 1. This means their immune system was already showing signs of attack, and their blood sugar levels were beginning to look abnormal. Scientists believe that at this stage, there is almost a 100% chance of being diagnosed with Type 1 over your lifetime.
Just over half the participants took Teplizumab, and just under half took a dummy drug. In those taking the dummy drug, 72% were diagnosed with Type 1 diabetes during the course of the study, with a median time to diagnosis of two years. In the Teplizumab group, 43% were diagnosed with Type 1, with a median time to diagnosis of four years.
So that’s a lower risk of Type 1, and roughly two extra years without the condition – no insulin therapy, and no underlying harm from high blood sugar levels. There are still many questions, and larger studies are now needed, but this is a real step forward.
Researchers believe that Teplizumab worked because the immune system had already begun to attack, and that it wouldn’t have worked in people who were earlier on in the development of Type 1. This raises interesting questions for how Teplizumab might be used in the future, with researchers perhaps looking to delay a diagnosis for as long as possible, rather than testing it in people with high genetic risk.
A spoon full of…insulin?
But other scientists are looking at these earlier stages of development with a different method: immune tolerance.
In Type 1 diabetes, the immune system mistakenly recognises and attacks specific molecules on the surface of insulin-producing beta cells in the pancreas. One of those molecules is insulin. So GPPAD scientists, who we mentioned earlier, want to find out if tiny amounts of insulin early in life could encourage the immune system to tolerate insulin, preventing it from attacking later on.
The trial is called POInT (Primary Oral Insulin Trial), and it’s testing if insulin powder mixed into food or milk can train the immune system to tolerate insulin and reduce the risk of the child developing Type 1.
POInT is recruiting babies (aged 4-7 months) who are at high risk of Type 1 diabetes and you can find out more about it.