New research presented at our professional conference (DUKPC) pinpoints combinations of genes that either help protect people living with obesity and overweight from developing type 2 diabetes, or increase their risk.
Obesity affects nearly two-thirds of adults in the UK and is a key risk factor for type 2 diabetes, but not everyone with a higher bodyweight will develop the condition. At DUKPC, our researchers presented new findings that shed light on why this is.
With Diabetes UK funding, Dr Hanieh Yaghootkar analysed genetic and health information from thousands of people. The team wanted to understand how combinations of genes that are linked with obesity can help to protect against or increase the risk of type 2 diabetes.
The results
The team identified three combinations of obesity-related genes that increase the risk of type 2 diabetes, and two that lower it.
The 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.
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.
The findings reveal that the groups of genes each impact where fat is stored in the body in unique ways. In turn, where fat is stored directly influences whether people with obesity are likely to develop type 2 diabetes or not.
In particular, fat in the liver was found to be important. The liver plays a crucial role in maintaining blood sugar levels and to function well it should contain little or no fat.
Personalised treatments
These findings could lead to improved prediction, prevention and more personalised treatment of type 2 diabetes.
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.
“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.”
Dr Elizabeth Robertson, our Director of Research, 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.”
