Roy Taylor: What’s next for DiRECT? – by Eddie Johnston

Until recently, we thought that type 2 diabetes was a lifelong condition. But in 2017, the results of the DiRECT study revealed that it is possible for some people to go into remission. Professor Mike Lean and Professor Roy Taylor revealed that through a weight management programme, it’s possible for some people with type 2 diabetes to have healthy levels of blood sugar without needing medication.

It’s an incredibly exciting discovery that’s already having an impact. It’s helped people like Shivali go into remission and avoid unpleasant side effects from her medication. And last month, Professor Taylor published a book called ‘Life Without Diabetes’ aimed at helping people better understand the development of type 2 diabetes and what remission means.

But there’s still plenty of research to do. While the results of DIRECT are exciting, there’s important questions that need to be answered.

Going global

DiRECT involved over 300 participants, but almost all of them were white and from the Tyneside and Glasgow areas. We need to be sure that the biology behind type 2 diabetes is not different across different ethnicities, and we don’t yet know if everyone can benefit from treatments like the one tested in DiRECT.

Professor Taylor wanted to find out if an approach similar to DiRECT could help black Caribbean people put their type 2 diabetes into remission. In a study published in Diabetic Medicine, the research team looked at 25 people in Barbados who were overweight and had been diagnosed with type 2 diabetes within the last six years.

In the UK, people of black African-Caribbean origin are up to three times more likely to develop type 2 diabetes than white people. Barbados also has particularly high rates of type 2 diabetes, so it’s vital we find treatments to help this high risk group.

Participants stopped taking diabetes medications and started a liquid diet of 800 calories a day for eight weeks. They were then supported by their healthcare team to gradually return to healthy eating, to help maintain their weight loss.

After eight weeks, people in the study had lost an average of 10kg, and a similar proportion had achieved normal blood sugar control to those in the 2011 Counterpoint study that led to the DiRECT trials. Eight months later, a majority of participants had kept both their weight and blood sugar levels down. Men were more likely to go into remission than women, as were those who lost more than 10kg.

The results of this 25 person study are promising, demonstrating that a DiRECT style approach is similarly effective across ethnicities. There’s more work to be done to see if a weight management programme could be implemented across the Caribbean to reduce the impact of type 2 diabetes.

The science behind the success

Another important question is how does weight loss lead to remission? Professor Taylor and the DiRECT team have already shown a link between weight loss and a reduction in the levels of fat inside the liver and pancreas.

As the levels of fat inside the pancreas reduce, the team found that the insulin-producing beta cells in pancreas can gradually start working again. It’s thought that this “re-booting” process is key to type 2 diabetes going into remission.

In a new study published in Cell Metabolism, Professor Taylor has been examining how the fat moves from the liver to the pancreas to damage beta cells. Fat is transported from the liver via the blood to all organs of the body in particles called ‘very low density lipoprotein’ (VLDL). In a person without type 2 diabetes, the liver produces only a small amount of VLDL. But if the liver builds up too much fat, it begins to move more to the rest of the body. This causes a build-up of fat in the wrong places – including the pancreas, stopping it from working properly.

The team studied 38 people who took part in the DiRECT study. In people who went into remission, they found that levels of liver fat had dropped. As a result, their liver was producing less VLDL, which coincided with less fat in the pancreas. In people who went into remission but redeveloped type 2 diabetes, they saw an increase in liver fat, an increase in VLDL produced by the liver and, as a result, increased pancreas fat.

This evidence suggests that type 2 diabetes could be a result of fat building up in the liver and pancreas and helps explain why weight loss leads to remission in some people.

ReTuning in

Understanding more about how remission works, both on a scientific level and in different groups of people, is absolutely vital to help as many people go into remission as possible. Professor Taylor is particularly interested in people with type 2 diabetes who aren’t overweight.

He thinks that weight loss could help, and that people develop type 2 diabetes if they store more fat than their body can cope with. He and his team will discover if low-calorie meal replacements can help people with type 2 diabetes who aren’t obese to put their condition into remission. The research team will then measure the amount of fat in the pancreas and liver, to give them a picture of how much of a role weight loss plays in remission in people who aren’t overweight.

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