Scientists say they have discovered what causes a condition which can lead to people with diabetes having to have lower limbs amputated.
People with diabetes are at risk of developing leg ulcers
A team from the University of Bristol identified changes in skin tissue which precede the development of leg ulcers.
Sometimes, ulcers will not heal and the only solution is to amputate, usually below the knee.
Diabetes experts said lowering blood pressure, cholesterol and glucose cut complications from the condition.
It is estimated that around 50,000 people with diabetes will have a foot ulcer at any one time, and up to 15% of all foot ulcers will result in amputations.
People with Type 2, or adult onset, diabetes are particularly at risk.
The condition often goes undetected, meaning high blood glucose levels, high blood pressure, lack of fitness and weight problems are not addressed, potentially causing damage to the circulatory system.
One circulatory disorder is peripheral vascular disease, which particularly affects people with Type 2 diabetes.
Their treatment can cost the NHS as much as £600m a year.
The researchers looked at 14 patients who had needed below-the-knee amputations.
They compared skin tissue from their amputated leg with some from their healthy leg.
It was found that damaging changes were occurring in the connective tissue that supports the skin.
The rate of tissue renewal was much quicker than normal and poor blood supply leads to abnormal collagen - the protein that is the main support in connective tissue.
This means the skin is not as strong as it should be and can break down more easily, allowing ulcers to form.
Understanding what happens in the tissue could allow doctors to develop treatments which prevent ulcers developing and therefore help patients avoid amputations.
'Prevention not alleviation'
Dr John Tarlton, who found the link in his research at Southmead Hospital in Bristol, said: "The results of our study have opened up new avenues that previously no-one knew existed and the ramifications are far reaching in terms of finding clinical treatments to save people's limbs."
He added: "We believe that the principles of this research may be applied to other disorders where the tissues are affected by oxygen deficiency, such as ischaemic heart disease.
"More investigations are needed to understand how widespread this problem is, but hopefully this breakthrough will mean that we can start looking to ways to improve the quality of a great many people's lives."
Andy Proctor, of Action Medical Research, said: "Understanding the mechanism behind the ulcers means that, finally, clinical care may be directed at the causes rather than the alleviation of the symptoms."
Amanda Eden, of the charity Diabetes UK, said: "This research is very promising and we will watch with interest for further work in this area.
"To help avoid complications of diabetes such as these, we would advise people to reduce blood pressure and cholesterol levels and aim to have good control of blood glucose levels."