From diabetes subtypes to genetics: the big research themes from DUKPC – by Faye Riley

Our annual conference was an inspiring and action-packed three days, crammed with research highlights. You can read about the latest on immunotherapies in our last DUKPC blog. Here I’m covering some of the big research themes that were the talk of the town.

Drilling down into subtypes

Professor Andrew Hattersley gave the conference’s most prestigious lecture on diabetes subtypes and the importance of getting diagnosis right.

We supported Professor Hattersley’s early research into monogenic diabetes, a rare type caused by a mistake in a single gene. His pioneering work transformed the way people with these rare types were treated: most were able to stop taking insulin and take tablets instead.

Today scientists have discovered 58 different subtypes of monogenic diabetes, helping people with these conditions to get the right diagnosis and the right treatment.

Professor Andrew Hattersley

But what about the more common types of diabetes? Professor Hattersley explained subtypes may exist there too.

With our funding, scientists at Exeter have found two different types of immune attack in Type 1 diabetes. Those diagnosed as young children appear to have an attack involving two types of immune cells, where their insulin-producing beta cells are rapidly destroyed. In teenagers and adults, it looks like their beta cells are destroyed at a slower rate.

This can help scientists design and tailor treatments to stop that immune attack (called immunotherapies) in the future; we might need a different approach depending on the age you’re diagnosed.

In Type 2 diabetes, subtypes could be more related to how people respond to treatments and how their condition progresses. For example, Professor Hattersley found that blood sugar levels rise year-on-year at a faster rate in people diagnosed with Type 2 under the age of 50, compared to after the age of 65.

We can also use characteristics like weight and gender to help predict how people will respond to treatments. For example, men of a healthy weight seem do better with Sulphonylureas, while women who are overweight do better with Thiazolidinediones.

Teasing apart subtypes of diabetes is an exciting idea that could help us to personalise treatments. But Professor Hattersley cautioned that subtypes will only stand the test of time if they inform treatment and improve diabetes health outcomes, and we don’t know this yet.

Painting a genetic picture

Dr Mike Weedon

Dr Mike Weedon highlighted the power of genetics, with huge genetic studies giving us the clearest understanding to date of how much our genes influence Type 2 diabetes. Scientists have found around 400 common changes to genes that make some of us more prone to developing Type 2, so it’s a complex picture.

Dr Hanieh Yaghootkar, one of our research fellows, recently added to that picture. They studied 451,000 people in the UK Biobank (one of the world’s largest health studies) to find variations in certain genes that were linked to levels of body fat.

They found seven new genetic changes that could lower a person’s risk of developing Type 2 diabetes. People with these changes were more likely to carry extra fat in safer places, preventing it from sitting around important organs, like the liver and pancreas.

Understanding Type 2 diabetes at a genetic level can help us find people most at risk, work out how to reduce their risk, and create new treatments to slow or stop the development of Type 2 diabetes in the future.

Genetics can also help with diagnosis. Dr Weedon and team are developing a simple genetic test to help doctors identify the type of diabetes in people where a diagnosis isn’t clear.

The test looks for different genetic changes which carry a small risk of Type 1 diabetes, and combines all these risks into a single score. If a person’s score is high, they are more likely to have Type 1 diabetes. If the score is low, they are more likely to have Type 2 diabetes. This could help avoid dangerous cases of misdiagnosis and make sure people are given the right treatment sooner.

Keep an eye out for our final DUKPC research blog, where I’ll be running through fear of hypos and exercise.

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