Researchers have uncovered five unique combinations of genes which either protect people living with obesity and overweight from developing type 2 diabetes or conversely increase their risk.
It appears to be associated with patterns of fat storage in the body particularly around the liver, they reported at the Diabetes UK Professional Conference 2023.
The research by a team at Brunel University London built on previous findings they reported showing that having higher levels of fat in the liver can increase the risk of type 2 diabetes.
In the latest study, using data from the UK BioBank cohort, they used precise measures of fat in different parts of the body, muscle quality and organ size combined with genetic evidence for distinct biological mechanisms linking higher adiposity with risk of type 2 diabetes.
They identified three combinations of obesity-related genes that increase the risk of type 2 diabetes, and two that lower it.
The gene combinations that increased the 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, delegates heard.
By contrast, 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.
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.
The researchers pointed out that type 2 diabetes is a complex condition with many risk factors but it is not yet fully understood why the majority of people with overweight and obesity do not develop type 2 diabetes.
Recent figures show cases of diabetes have risen to more than 5 million for the first time in the UK.
Concerns had been raised that increased levels of overweight and obesity were fuelling the rise, alongside social deprivation factors.
Study leader, Dr Hanieh Yaghootkar at Brunel University London, said understanding this better could lead to more targeted prevention or intervention: ‘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 Elizabeth Robertson, director of research at Diabetes UK, who funded the study, said: ‘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.’
