Being unable to store excess fat safely in the body increases the risk of type 2 diabetes, heart attacks and strokes, Cambridge University research suggests.
A study of 200,000 people showed that those with a variation in their genetic make-up were less likely to deposit fat under the skin in the lower body.
This can lead the body to become resistant to the hormone insulin.
The scientists said their findings explain why even slim people who eat too much and are inactive are at risk.
And they added that a healthy diet and physical exercise is important, regardless of body weight.
Insulin is a hormone that controls levels of blood sugar.
When the body becomes resistant to it, levels of blood sugars and lipids rise, increasing the risk of diabetes and heart disease – but no-one is sure why insulin resistance happens and why some people become resistant when overweight, and others do not.
International figures show that 43% of people who develop type 2 diabetes are obese, 43% are overweight and 14% have a healthy weight.
The Cambridge study, published in Nature Genetics, found that a large proportion of the population has inherited some of 53 separate genetic variants that inhibit the storage of fat safely under the skin, particularly in the lower half of the body.
Their fat is more likely to end up in the bloodstream or stored in and around the body’s central organs.
The study said people who have more of this genetic material are at much greater risk of type 2 diabetes – no matter what their BMI (body mass index) is.
In the 20% of the population with the highest number of these genetic variants, their risk of diabetes rose by 39% compared to the 20% of the population with the lowest genetic risk.
People with fat storage problems can end up with fat accumulating in and around the liver, pancreas and muscles – where it causes insulin resistance and eventually type 2 diabetes.
Dr Luca Lotta, from the Medical Research Council epidemiology unit at the University of Cambridge, said that fat stored in the arms, legs and under the skin played an important role.
“Our results highlight the important biological role of peripheral fat tissue as a deposit of the surplus of energy due to overeating and lack of physical exercise.”