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(46) Diabetes

 Pancreas transplantion

Pancreas transplant



 I should like to volunteer to have a pancreas transplant. Is there someone I must apply to? How successful have these operations been?

Pancreatic transplantation is still in the experimental stages and it will be difficult to find anyone who will accept you as a volunteer. Technically, pancreatic transplants are even more difficult than liver, kidney or heart transplants. The pancreas is very delicate and, as the seat of many digestive juices, has a tendency to digest itself if damaged even slightly. The duct or passageway through which these juices pass is narrow, and has to be joined up to the intestines in a very intricate way so that the enzymes do not leak. Even if everything goes well technically, the body will still react against transplant so several immunosuppressant drugs have to be given. Some of these (particularly steroids), given in high doses to suppress rejection of the transplant tend to cause diabetes or make existing diabetes worse! The future looks much more promising with the transplant of the islet cells of the pancreas.

Are there any hospitals carrying out transplants of the islets of Langerhans? Would I be able to donate my cells to my insulin-treated daughter?

Yes, there are seven centres around the UK that have signed up to the Diabetes UK Islet Transplantation Consortium. This consortium is hoping to replicate and refine the technique developed by the English surgeon, James Shapiro, and his team in Edmonton, Canada. The Edmonton team took islet cells from donor pancreases and injected them into the liver of people with Type 1 diabetes. Once in the liver the cells developed a blood supply and began producing insulin. The entire transplantation process is now known as the ‘Edmonton Protocol’.

However, it is not possible to take islets from living donors so you would be unable to donate your cells to your daughter. This technique is still in the experimental stage but the results look promising. In Edmonton, 13 out of 15 islet cell transplants have been 100% successful, but until the people have lived with the transplants for a number of years it is difficult to know whether this can be seen as a cure.

Transplant of the islets of Langerhans still involves the use of drugs to prevent rejection of the new cells (immunosuppressive therapy), and as result only people who have extreme problems in controlling their blood glucose levels are being considered for transplantation. People who receive islet cell transplantations spend the rest of their lives taking immunosuppressive drugs, and the long-term effects of taking these drugs are not yet known and may be damaging.

Research into ‘microencapsulation’ of these islets is making some progress, and may one day offer a solution that will avoid lifelong immunosuppressive therapy. By enclosing the islets in a porous membrane and transplanting them into an animal with diabetes, it is possible to show that the insulin can get out of the ‘bag of islets’ and normalize the blood glucose at the same time as nutrients from the bloodstream can get in to sustain the islets – while this is going on the membrane keeps at bay the cells responsible for tissue rejection. Unfortunately, after a while, the membrane tends to get clogged with scar tissue and the islet graft stops working.

A few years ago there was excitement in the media about an article in the medical journal, The Lancet, reporting a successful transplant of encapsulated islets. The man who received the transplant was still being treated with immunosuppressant drugs as he had received a kidney transplant as well. This result was encouraging, but much more research still has to be done before this could be considered as a form of treatment for diabetes. Until there has been a major breakthrough in the transplantation of tissues from one individual to another, the hazards of long-term immunosuppressive therapy for someone receiving either a pancreas transplant or an islet cell transplant are greater than those of having diabetes treated with insulin. There are no tangible benefits yet for this form of therapy as a primary form of treatment for diabetes. The problems are not insuperable but much more research needs to be done before transplantation becomes a routine treatment for diabetes. Insulin pumps and artificial pancreas

I recently read about a device called a ‘glucose sensor’, which can control the insulin administered to animals with diabetes. Will this ever be used on humans and if so what can we expect from it?

The research into the development of a small electronic device that could be implanted under the skin and that could continuously monitor the level of glucose in the blood has been going on in the USA, the UK and several other countries for many years. The technical problems of such a device are, however, considerable, and it seems unlikely to be of use in people with diabetes for at least some time. Not only are there technical problems in achieving an accurate reflection of blood glucose level by such a subcutaneous implanted glucose sensor, but the further problem of ‘hooking it up’ to a supply of insulin to be released according to the demand is formidable. Clinical trials are being carried out in the USA and France using an intravenous glucose sensor in conjunction with an implantable pump. The early results are encouraging, but it will be several years before it is widely available.

I understand that there are ways of testing blood glucose without pricking the skin. Can you tell me more about them?

There are regular reports in the press about ‘non-invasive’ blood glucose monitoring devices being developed. Some devices being developed are not totally non-invasive. One involves a needle being inserted under the skin for up to 3 days at a time so that blood glucose readings can be taken every few minutes. At the moment the readings given can be accessed only by a healthcare professional, but it is hoped that eventually people would be able to read these results for themselves. This method of monitoring could be useful if the device were attached to an insulin pump adjusting the amount of insulin administered in response to the blood glucose level. Although this is not yet possible, it is likely to be developed in the very near future.

The other non-invasive blood glucose monitoring device is the GlucoWatch, developed by a Californian company called Cygnus Inc. This device is worn like a wristwatch and measures blood glucose from interstitial fluid. Interstitial fluid is the fluid that fills blisters when skin is damaged, and it can be extracted from the top layers of skin without the use of a lancet. It works by a process called reverse iontophoresis. This means that a very low electric current is applied to draw interstitial fluid through the skin. The glucose in the fluid is then collected in a gel that is part of the AutoSensor, which gives a glucose measurement. The AutoSensors must be replaced every 12 hours, and the device then needs a 3-hour warm-up period. The device must be calibrated against a finger-prick blood test each time a new AutoSensor is used. The readings are taken up to three times an hour. It has a memory that can store up to 4000 results. It is recommended that people do not alter medication based on a GlucoWatch result without checking this against a finger prick test. It is now available in the UK from Cygnus (UK) Ltd, but it is expensive.

Diabetes UK Careline can provide an information sheet on the product.

I hear that there are pumps available that can be implanted like pacemakers – is this true? What are the likely developments with insulin pumps within the next 5 years?

Yes, it is true that insulin pumps have been implanted into people as part of research studies and there has been some encouraging progress in this field. Although still experimental and with a long time to go before being a regular form of treatment, some pumps have been developed that are small enough to be implanted into the muscles forming the wall of the abdomen and have been left there for several years. The implantable pump is licensed for sale in Europe but is currently not available in the UK, and it has not been approved by the FDA in the USA. It is made by MiniMed and is very expensive. This pump does not have a sensor to detect glucose; it simply infuses insulin at a slow rate that can be regulated from the outside using a small radio transmitter. This can be used to command the pump to infuse more insulin just before a meal, or to reduce the rate of infusion if the blood glucose readings are too low. The pump has a reservoir of insulin that can be refilled with a syringe and needle, through the skin, without too much trouble, but changing the batteries requires an operation! Although it looks promising, the major disadvantages are cost and complexity. This is still very much a research procedure and cannot yet be recommended for routine treatment.

I have heard about the artificial pancreas or ‘Biostator’. Apparently this machine is capable of maintaining blood glucose at normal levels, irrespective of what is eaten. Is this true? If so, why isn’t it widely available?

There are several versions of what you describe, namely an artificial pancreas, which measure the glucose concentration in the bloodstream continuously and infuse insulin in sufficient quantities to keep the blood glucose normal. Unfortunately these machines are technically very complex, bulky and extremely expensive. Their major value is for research purposes since they are quite unsuitable at present as devices for long-term control. There is a great deal of research going on in several bioengineering groups to try and make them the same size as a cardiac pacemaker, but it is still likely to be several years before the first machines become available for research studies, and it will be a long time after that before suitably reliable machines are available for daily treatment. Even when the technical problems have been resolved and it has been miniaturized to an acceptable size for implantation, the costs are likely to be a limiting factor.



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