Research is stepped up as diabetes rate rises

The incidence of diabetes is climbing and doctors do not know why. The number of people with the disease has been doubling every 10 years over the past few decades. The disease has severe impact on the patient and on society.

"Diabetes is down the list in terms of visibility but very high in terms of the health costs," stated Dr John Nolan, founder of the metabolic research unit and a consultant in diabetes at St James's Hospital, Dublin.

It is a disease in which the body's own protection system against infection begins to attack healthy tissues in the pancreas, the islet cells which produce the hormone, insulin.

The foods we eat are converted to sugars which circulate in the bloodstream, and insulin enables muscle, liver and fat cells to use this energy source.

Without insulin, blood sugar levels rise dangerously and over time much damage can be caused.

Diabetes is recognised as having two forms, Dr Nolan explained. Type I typically affects younger people and requires treatment by insulin injections. Type II, or late onset, diabetes traditionally occurred in older patients and could be treated by oral drugs and by modifying diet.

About 3 per cent of the Irish population has diabetes and 90 per cent of these are Type II.

This picture is changing, however, with Type II increasing rapidly amongst adolescents and children, as first reported by Dr Nolan and colleagues in California in 1997. "We are now seeing younger patients with Type II diabetes in Dublin," he said.

When the immune system attacks something, it leaves behind telltale signs in the form of antibodies. Dr Nolan and his colleague in the metabolic research unit, Dr Elaine Murphy, developed "assays" based on technology known as the ELISA test, which can help show whether the pancreas is under immune system attack.

The research is funded in part by Eli Lilly & Co (Ireland) Ltd.

Two assays are in use, one for antibodies against glutamic acid decarboxylaise (GAD), an enzyme released when there is damage to pancreatic cells, and one for antibodies against insulin, which can also be attacked by the immune system. A third is under preparation, an assay that looks for antibodies against islet cells.

The tests require a small amount of blood and take only a day, but can provide doctors with a wealth of information about their patients. "The real thing is to avoid misclassification," Dr Nolan said.

About 70 per cent of Type I patients have antibodies, which would have been expected given auto-immune damage to the pancreas. Surprisingly, a tenth of Type II patients also have these antibodies. Having this information early is important because it shows that damage to islet cells is under way, but also because it has been found that giving insulin at this stage helps to switch off or moderate the immune attack on the pancreas.

"In general terms, the patient will benefit from earlier insulin," Dr Nolan said. Yet doctors do not want to give insulin when dietary changes or oral medication are sufficient. The tests help to make sure that the best treatment is given as early as possible after diagnosis.

Another facet of the unit's research activity relates to new drugs which help to increase the body's sensitivity to insulin. These are very useful in Type II patients who still have some level of insulin production. While their insulin output may drop, these drugs ensure that the insulin which is in circulation is used to maximum potential.

While having tests which can show pancreatic cell damage is important in deciding the best clinical approach, the real power of these tests would come if medical treatments could be developed to block destruction of the islet cells.

The diabetes-related antibodies begin to appear long before the patient begins to show clinical signs of the disease. These blood tests can indicate a pre-diabetic state in very high-risk individuals, for example, an identical twin whose sibling has the disease.

Trials aimed at preventing islet destruction are under way in several countries. While no intervention has yet proved effective, having an assay in place to identify at-risk patients is an essential tool for doctors.