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Liver fat directly raises risk of type 2 diabetes

Our research has revealed that having higher levels of fat in the liver, and having a smaller pancreas, directly increase the risk of developing type 2 diabetes. The findings provide a significant step forward in understanding the biological causes driving the development of the condition.

This research could unlock new treatment approaches and allow more tailored ways to help people reduce their risk of type 2 diabetes, as well as prevent cases altogether.

Two scientists in white lab coats with their backs to camera, looking at a computer screen together

 

Is liver fat causing type 2 diabetes?

Researchers, funded by us and led by our research fellow Dr Hanieh Yaghootkar, at Brunel University, explored whether liver and pancreas size and fat content could play a direct role in causing type 2 diabetes. They used Mendelian randomisation – a statistical method that uses genetic and health information to understand cause and effect.

The team looked at data from 32,859 people who had had MRI scans as part of the UK Biobank study. Liver and pancreas fat and size were analysed from these scans, alongside information about genes that affect them. This was to understand their role in the risk of developing diabetes.

Research findings

The researchers found that people with a genetic make-up that makes them prone to storing fat in their liver are more likely to have type 2 diabetes. This suggests that higher liver fat levels directly increase the risk of type 2 diabetes, with their analysis showing that for every 5% increase in liver fat, the risk of type 2 diabetes increases by 27%. Similarly, having a smaller pancreas was found to have a direct role in causing type 2 diabetes.

Pancreas fat levels and liver size were associated with type 2 diabetes but were not found to play a direct role in raising type 2 diabetes risk. The researchers also looked at data from 9,000 people with type 1 diabetes, but liver and pancreas size or fat levels were not found to be directly linked to the autoimmune condition.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) occurs when fat builds up in the liver. NAFLD is most commonly seen in people living with obesity or overweight, and having higher levels of liver fat has previously been associated with the development of type 2 diabetes. However, this is the strongest evidence to date to suggest liver fat and pancreas size have a hand in causing the condition.

Type 2 diabetes is a complex condition with many risk factors, some that can’t be changed such as age, ethnicity and family history, and some that can, such as body weight. Previous research has shown that losing weight can reduce liver fat levels in people with type 2 diabetes. Piecing together how different factors impact the risk of developing type 2 diabetes is important in understanding the most effective ways to help people reduce their risk.

In future, those with a certain genetic makeup that may make them prone to higher liver fat levels or a smaller pancreas could be offered tailored support to help them take steps to reduce their risk of type 2 diabetes early on.

Our RD Lawrence Fellow, Dr Hanieh Yaghootkar at Brunel University, said:

People with type 2 diabetes usually have excess fat in their liver and pancreas, the two key organs in the maintenance of the normal level of blood sugar. The genetic analysis we used in this study is the best possible method to test this relationship and we provided evidence for a causal role of liver fat in type 2 diabetes risk.

“Our results encourage better treatment of those living with non-alcoholic fatty liver disease, and provide evidence for the multiple benefits of weight loss and better screening for diabetes risk in these people.

“We also showed that people with genes that make them more likely to have a smaller pancreas have a higher risk of type 2 diabetes. These results suggest that underlying mechanisms associated with reduced pancreatic volume precede diagnosis of type 2 diabetes.

“We hope by better characterisation of fat in different organs and also different organ size in the future, we can provide better understanding of the mechanisms that cause type 2 diabetes.”

Dr Lucy Chambers, our Head of Research Communications, said:

 

We know from Diabetes UK’s landmark research on type 2 remission that liver and pancreas fat and size are linked to type 2 diabetes, but until now, it was unclear whether either of these factors played a direct role in causing type 2 diabetes.

"This important research funded by Diabetes UK pinpoints, for the first time, that liver fat and pancreas size directly contribute to an increased risk of developing type 2 diabetes and this is hardwired into our genetics. However, it’s important to remember that a complex mix of genetic, biological and environmental factors contribute to the development of type 2 diabetes. Knowing your overall risk of type 2 diabetes is the first step in accessing support, such as prevention programmes, to help reduce your risk.

“Dr Yaghootkar’s research offers new insights into the causes of type 2 diabetes that, as we move towards an era of personalised medicine, could in future help us to improve the way we predict, prevent and treat the condition.”

You can find out your risk of type 2 diabetes and steps you can take to reduce it, by visiting our free online Know Your Risk tool.

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