LONDON (Reuters) 09:28 AM ET 01/07/98 – American scientists believe they may have found another clue to why people develop diabetes, the fourth leading cause of death in most developed countries.

Researchers at Brigham and Women’s Hospital and Harvard University in Boston have shown that the progression of the disease is linked to a set of T-cells that fail to produce a substance called interleukin 4 (IL-4), which sends signals to the immune system.

The findings, published in the scientific journal Nature, could have important therapeutic implications and may be one of the final obstacles to conquering the disease.

“This work provides some insight into what the role of this new population of T-cells might be, but it is too early to call this the missing link,” said David Hafler, who, with Jack Strominger, led the research team.

“Not a lot is known about them,” he told Reuters. “They (the subset of T-cells) are markedly decreased in type 1 diabetics and more striking than their decrease is that they stop making IL-4.”

T-cells play an important role in the body’s immune response. Previous experiments on animals have shown that IL-4, produced by specific T-cells, could prevent diabetes.

Hafler’s study of identical twins and triplets is the first to show that the hypothesis holds up in humans. He stressed that it is a small study that needs to be confirmed by others. If his findings are confirmed, the next step would be to find out what triggers the production of IL-4.

“We’re doing experiments now to determine what we can do to signal the T-cells from the diabetics to make IL-4 at a biochemical level,” he said.

Diabetes is caused by a deficiency in the production of insulin, the hormone that controls human metabolism and blood sugar levels. Sufferers of type 1, or juvenile onset diabetes, must have insulin injections to control the auto-immune disease. Their own T-cells help to destroy cells in the pancreas that secrete insulin.

Type 2 diabetics have abnormal insulin responses. Diet, exercise and drugs to stimulate pancreatic secretions of insulin are used to treat the milder forms of the disease.

Although the T-cell attack explains how the disease develops in type 1 diabetics, it does not answer the question of why some people predisposed to the disease, such as identical twins whose siblings are sufferers, do not get it. Hafler and his colleagues may have found one of the reasons.

“The immune system is a complex series of events and we are slowly dissecting the various components that may be involved,” he said in an interview.

Diabetes, which causes kidney failure, strokes, heart attacks, blindness and nerve damage, affects 135 million people throughout the world and kills 2.8 million every year.

Experts estimate the number of sufferers will double to 220 million by the year 2010.