Brunel University London: Liver fat directly linked to type 2 diabetes, new study shows

The researchers found that every five per cent increase in liver fat increased the risk of a person developing type 2 diabetes by 27 per cent. The findings provide a significant step forward in understanding the biological causes driving the development of the condition

Funded by Diabetes UK and led by Brunel’s Dr Hanieh Yaghootkar, the researchers used Mendelian randomisation – a statistical method that harnesses genetic data to understand cause and effect – to identify whether liver size, pancreas size, and fat content could play a direct role in causing type 2 diabetes.

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, indicating that higher liver fat levels directly increase the risk of type 2 diabetes. Similarly, having a smaller pancreas was also found to have a direct role in causing type 2 diabetes.

“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,” said Dr Yaghootkar, a Diabetes UK RD Lawrence Fellow at Brunel, who worked alongside colleagues from the University of Exeter, the University of Westminster, CALICO and the University of Glasgow.

“The genetic analysis we used in this study is the best possible method to test this relationship and we showed that liver fat is causal for type 2 diabetes. 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.”

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

Non-alcoholic fatty liver disease (NAFLD) occurs when fat builds up in the liver. NAFLD is most commonly seen in overweight and obese people and having higher levels liver fat has previously been associated with development of type 2 diabetes. However, the new study provides 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 bodyweight. 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.

Dr Lucy Chambers, Head of Research Communications at Diabetes UK, which funded the research, 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.”

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