Researchers have identified five obesity-related genes that can either trigger the development of type 2 diabetes or combat the condition.
Speaking at the Diabetes UK Professional Conference 2023, Dr Hanieh Yaghootkar and a team of academics from the University of Westminster and Calico Life Sciences, presented new research that shows the obesity-related genes that increase the risk of type 2 diabetes were linked to higher levels of liver fat, and vice versa.
The results highlight that patterns of fat storage – in particular, fat in the liver – play a crucial role in determining whether people with obesity are likely to develop type 2 diabetes or not.
During the study, the research team examined data from the UK Biobank to recognise how obesity-related genes increase the risk, or protect against type 2 diabetes.
They detected two combinations of obesity-related genes that lower the risk of type 2 diabetes and three that increase it.
According to the research, the two protective genetic combinations were linked to lower levels of liver fat, better insulin sensitivity, a healthy metabolism and lower risk of heart disease.
Combinations that increased risk of type 2 diabetes were also linked to high levels of fat in the liver, insulin resistance, problems in the way the body changes food into energy (metabolism) and higher risk of heart disease.
All five gene combinations were associated with a history of childhood obesity, higher BMI and higher levels of fat under the skin, and in the pancreas and muscles.
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The findings reveal five distinct groups of genes that each impact where fat is stored in the body in unique ways, which in turn directly influences risk of type 2 diabetes in people with overweight or obesity.
Dr Hanieh Yaghootkar at Brunel University London, said: “There is increased focus on weight loss to manage type 2 diabetes.
However, individuals with the same total levels of body fat have different risks for weight-related health conditions such as type 2 diabetes, hypertension and cardiovascular disease.
“Identifying different patterns of fat distribution in the body and their relationship with type 2 diabetes is important for improving risk assessment, understanding underlying mechanisms, developing personalised medicine, and preventing the condition and its complications.”
Dr Yaghootkar added: “In this study, we used precise measures of fat in different parts of the body, muscle quality and organ size and provided genetic evidence for distinct biological mechanisms that causally link higher adiposity with risk of type 2 diabetes.”
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Dr Elizabeth Robertson, Director of Research at Diabetes UK, which funded the study, said: “Type 2 diabetes is a complex condition with many risk factors, and while living with obesity or overweight is a major risk factor, not everyone with a higher bodyweight will develop the condition.
“This research takes us a step closer to understanding the role that genetically determined patterns of fat storage play in obesity and type 2 diabetes, revealing why some people with higher bodyweights develop type 2 diabetes, whereas others are naturally protected.
“It’s important to remember that people with obesity who have genes that increase their type 2 diabetes risk can still take steps to reduce it, including by losing weight to reduce levels of fat in their liver.
“Early and accurate identification of those who are at greater risk of type 2 diabetes could help improve the way we predict, prevent and treat the condition, and identify those who might benefit from targeted treatment approaches.”
