Type 1 diabetes usually begins in childhood or young adulthood. In it, the immune (defence) system destroys the beta cells in the body. Beta cells, found in the Islets of Langerhans within the pancreas, are the cells that make insulin. Once these cells are destroyed, people with type 1 diabetes must inject insulin several times a day to control blood glucose levels.
Treatment of type 1 diabetes had not changed greatly since the discovery of insulin 90 years ago. While insulin formulations and delivery devices improved over time, insulin injections are still necessary.
Beta cells – these cells make insulin, which is secreted into the blood stream to regulate blood glucose levels.
Islets of Langerhans – clusters of cells found in the pancreas gland. The islets contain several types of cells that make different hormones, including the beta cells that make insulin.
Hypoglycemia – an abnormally low blood glucose level that exposes the individual to potential harm.
Severe hypoglycemia –
an episode of low blood glucose that is so low the person cannot treat it alone, but must be helped by someone else, usually a relative, paramedic or other health care professional.
Hypoglycemia unawareness – in this situation, the symptoms of hypoglycemia (shaking, sweating, hunger, palipations, tremor) are reduced or lost completely, or only appear at very low levels when brain function is affected. Hypoglycemia is more common after many years of type 1 diabetes or in people who have frequent episodes of mild hypoglycemia. Symptoms can usually be restored if hypoglycemia is carefully avoided.
However, giving replacement beta cells to those with type 1 diabetes ideally means injections will no longer be necessary. Another benefit is that transplanted islets only produce insulin when blood glucose levels are high. This provides more stable blood glucose levels and avoids hypoglycemia (low blood glucose).
Next, the islets (which make up five per cent of the pancreas gland) are extracted in a highly specialized laboratory.
The actual islet transplant procedure is done in the X-ray department. A local anesthetic is used. A needle is placed into the portal vein in the liver. The islets are released and begin to make insulin straight away.
The islet transplant is a minor procedure. However, it does carry risks of bleeding from the needle puncture, or of blood clots forming in the veins in the liver. Plugging the needle hole and using medications to thin the blood lessens these risks. There have been no deaths related to the procedure in Canada.
The immune system marks the islets as foreign. Just like people who have heart or kidney transplants, islet recipients must take anti-rejection drugs for the rest of their lives. These drugs carry some risks, including infections and some cancers. Due to this, and the limited supply of organ donors, islet transplants are reserved for people with type 1 diabetes at greatest risk from their disease.
Drugs used now have far fewer side effects compared to when the Edmonton islet transplant program started. The most common side effects are headaches, tremor and diarrhea. Usually these can be avoided by adjusting the medication dosage. Some anti-rejection drugs can cause some decline in kidney function.
The major benefits of islet transplantation are in providing stable blood glucose levels and preventing hypoglycemic reactions. People with type 1 diabetes who have frequent episodes of severe hypoglycemia (which can be life threatening) are likely to benefit most. Certain people no longer have warning symptoms alerting them to low blood glucose levels (hypoglycemia unawareness). They too are at high risk for severe hypoglycemia and should also benefit. Other candidates are those developing severe complications from diabetes who cannot tighten blood glucose control without episodes of severe hypoglycemia.
Currently, islet transplants are not done on children. Concerns exist about the long-term safety of drugs used to prevent rejection, and whether transplanted islets can meet the body’s demand for insulin as the child grows.
Islet transplants are not done on people with type 2 diabetes. Most people with type 2 diabetes can still make insulin. However, the cells of the body are not very responsive to it. This is called insulin resistance. People who have type 2 diabetes and take insulin often need large doses — more than one unit per kilogram of body weight per day. An islet transplant would not deliver enough insulin, or would become exhausted quickly. For these reasons, islet transplants focus on people whose bodies do not make insulin rather than those whose bodies do not respond to it.
It is not safe for women who are pregnant or planning to become so to take anti-rejection drugs. The drugs are also not safe for those with cancer or chronic infections like TB or HIV. People who have kidney damage from diabetes may not be suitable for islet transplant. Instead, a kidney-pancreas transplant might be the preferred treatment. Finally, those who misuse substances or smoke are not eligible.
Islet transplantation can be extremely effective in allowing people with type 1 diabetes to achieve near-normal blood glucose levels with no risk of hypoglycemia. Although almost all recipients can stop insulin injections, it may be only for a period of time. It could be as short as a few weeks, or last more than ten years. By five years, almost half of patients need to take some insulin to assist islet function. Still, this is usually a very low dose taken once a day. It compares well with four or more injections per day before the transplant. Even if some insulin is required, the presence of working islets protects from hypoglycemia, helping to achieve excellent blood glucose control.
Some transplants do stop working. It is not always clear why this happens, though research is focused on trying to understand it. In some cases, the body rejects the foreign cells. Other problems may be due to the destructive type 1 diabetes process by the immune system.
Early in the program, some people had severe side effects from the drugs and could no longer take them. Their transplants stopped working. However, less than 20 per cent of people have had transplants that have stopped working after some period. Although disappointed, many comment that they enjoyed the holiday from diabetes.
Since the islet transplant program is funded in Edmonton as part of Alberta Transplant Services and in Vancouver by B.C. Transplant, there is no cost to patients. Patients from across Canada are eligible to apply. Although most provinces cover the costs of anti-rejection drugs, a few do not or exclude islet transplant recipients.
Patients usually need to budget for the cost of travel and around four weeks of living expenses while in Edmonton or Vancouver. Costs and coverage are always explored with possible recipients ahead of time.
Although you can fill in an application yourself (available at www.islet.ca), we encourage contacting your health care team first. Other conventional approaches should be tried before moving forward with islet transplantation. Referrals from specialists or diabetes educators are helpful in deciding priorities for assessment appointments.
In general, applicants should have tried or be using modern insulin analogs (such as Humalog®, NovoRapid® or Apidra® with Lantus® or Levemir®) as part of a multiple dose regimen (four or more shots per day) or through an insulin pump. They should understand how to count carbohydrates and adjust insulin doses for activity.
Remarkable improvements have made islet transplants safer and more successful over the last ten years. However, many questions remain. Much research is focused on refining anti-rejection treatments so they are more effective, but have fewer side effects. Other treatments are being developed to maintain the health and function of transplanted islets so they will work longer. One possibility involves using a new site for transplantation, allowing islets to be inserted into a pouch under the skin. In the long term, the hope is to generate alternate sources of islets (such as stem cells) and avoid the need for life-long drugs to prevent rejection.
Even if you do not have type 1 diabetes, your help is needed. Many islet transplant recipients in Canada heard about the process either from a friend or an article like this one. Pass this article on to someone you know with type 1 diabetes.
Please sign your donor card, and encourage friends and family to do the same. The shortage of donor organs is a major problem. Every year people die while on the waiting list.
You may wish to make a donation to support diabetes or islet transplant research. Several charities support diabetes research, including the Alberta Diabetes Foundation, Juvenile Diabetes Research Foundation, and the Canadian Diabetes Association. Donations can also be made directly to the Islet Transplant Program in Edmonton or Vancouver.
Visit www.islet.ca or www.transplant.bc.ca/islet_cell.htm for information and links to additional resources. On the http://goo.gl/WrI7O website, doctors Ray Rajotte and Peter Senior describe the procedure in a short video sponsored by the Canadian Institutes for Health Research.