Mr Murat Akyol, Consultant Transplant Surgeon, Royal Infirmary of Edinburgh
What is the pancreas and why is it transplanted?
The pancreas is an organ inside the abdomen that consists of two different types of tissue with two separate functions. Most of the pancreas is a gland that produces a fluid rich in chemicals that help you to digest food. About 2-3% of the pancreas consists of clusters (tiny islands or islets) of cells that secrete small amounts of hormones into the blood stream. The most important of these hormones is insulin. A lack of insulin causes diabetes. Pancreas transplants are performed to treat diabetes.
Are there different types of diabetes?
The blood sugar level is controlled by insulin. There are two types of diabetes which occur when the body is either unable to produce insulin or is unable to respond to it.
Insulin dependent diabetes mellitus (IDDM or type I diabetes) tends to occur in children and young adults. It happens because of the destruction of insulin producing cells in the pancreas. Non insulin dependent diabetes (NIDDM or type II diabetes) occurs in middle or old age and is much more common. It occurs because the body becomes resistant to the actions of insulin and is unable to adequately compensate for this by increasing insulin production from the pancreas.
Can all diabetic patients by treated by pancreas transplant?
No. Pancreas transplantation is only suitable for patients with type I diabetes.
What does pancreas transplantation offer to a diabetic individual?
Individuals with type I diabetes require life long treatment with regular injections of insulin. Pancreas transplantation is the only treatment for diabetes that can offer complete insulin independence and normal blood sugar levels. After a successful pancreas transplant, patients do not need insulin injections, have no special dietary requirements, do not need to check their blood sugar levels regularly and are not at risk of developing low blood sugar levels (hypoglycaemia).
It is known that complications of diabetes – such as blindness due to retinopathy, kidney failure due to nephropathy, foot ulcers, digestive problems, abnormalities of heart rhythm or hypoglycaemic unawareness due to neuropathy and circulation problems – are related to blood sugar control. Strict and good control of blood sugar in diabetic individuals is associated with a delay in the onset of complications and a reduction in their severity, perhaps even prevention of some complications. Since pancreas transplantation offers excellent blood sugar control, it should also benefit diabetic patients by preventing or alleviating some of the complications of diabetes.
Is pancreas transplantation always effective to prevent diabetic complications?
There is a degree of uncertainty about this. There has been no controlled clinic trial directly comparing pancreas transplantation with insulin treatment in 2 similar groups of diabetic patients. We therefore rely on indirect evidence rather than scientific proof that pancreas transplantation may be better than insulin treatment for the prevention of diabetic complications.
There is a large amount of indirect evidence supporting the benefit of successful pancreas transplantation on some of the long term complications of diabetes. It is possible to conclude with a reasonable degree of confidence that successful pancreas transplantation will prevent or even reverse early changes in diabetic kidney disease. There is also reasonably good evidence that successful pancreas transplantation can prevent or partially reverse diabetic neuropathy. The symptoms of neuropathy are multiple and varied and include vomiting, diarrhoea or constipation, tingling and numbness of hands and feet, neuropathic ulcers of the feet, some abnormalities of the heart rhythm and hypoglycaemic unawareness. These complications may be prevented or if they already exist, may be improved to some extent with successful pancreas transplantation.
Another important complication of diabetes is retinopathy which can progress to blindness if untreated. Successful pancreas transplantation does not change the course of retinopathy within the first few years after the transplant. In fact in some patients with non proliferative retinopathy or untreated, unstable proliferative retinopathy, pancreas transplantation may cause rapid progression of retinopathy. For most patients with stable and treated retinopathy, pancreas transplant may offer a marginal benefit more than 5 years after transplantation compared with staying on insulin.
What other benefits can diabetic patients expect from pancreas transplantation?
There is little doubt that diabetic patients with kidney failure will have a better life expectancy if treated with kidney transplantation compared with staying on dialysis. Most studies have shown that diabetic patients receiving simultaneous kidney and pancreas transplants have better long term survival prospects compared with diabetic patients receiving only kidney transplants. Some of this difference may simply be because of patient selection. In other words it is likely that younger and fitter patients will be treated with simultaneous pancreas/kidney transplantation whereas older and less fit patients are more likely to be treated with only kidney transplantation.
We rely on indirect evidence again which suggests that addition of pancreas transplantation to kidney transplantation may genuinely improve long term life expectancy for diabetic patients.
Are all individuals with type I diabetes offered pancreas transplantation?
No. For the large majority of patients with type I diabetes, life long treatment with insulin injections is still safer than pancreas transplantation.
Transplantation of the pancreas involves a major operation which has potentially some complications and even a small chance of death.
Very importantly there are also risks related to the medication that patients need to use after transplantation. All organ transplants, including pancreas transplants, involve the transfer of foreign tissue to individuals. This foreign tissue is normally rejected by the immune system. It is therefore necessary to use medication to suppress the immune system and prevent the rejection of transplanted organs. These medicines (immunosuppressant drugs) are potentially sinister and dangerous medicines with important and even life threatening side effects and they need to be used indefinitely (for as long as the transplant lasts).
Therefore despite the difficulty and inconvenience associated with insulin treatment, insulin is still a safer drug for most patients with type I diabetes compared with pancreas transplantation and immunosuppressive drugs.
Which type I diabetic patients are suitable for pancreas transplantation?
There are mainly two groups of patients. By far the most common are those patients with diabetes who have developed kidney failure as a result of diabetic nephropathy. Such patients will require kidney transplantation – which is a much better treatment than dialysis. Since these patients will require immunosuppressive medication after their kidney transplant, they can also be given a pancreas transplant at the same time as the kidney, the so called simultaneous pancreas/kidney transplantation. This is the most common way to perform pancreas transplants for patients with type I diabetes.
If a patient with type I diabetes has already received a kidney transplant (perhaps from a live donor), hence they already require immunosuppression, they can subsequently undergo a second operation to give them a pancreas transplant. This is called pancreas after kidney transplantation.
A much less common application of pancreas transplantation is for patients who do not have kidney failure but have life threatening complications with insulin treatment. This occurs in individuals with hypoglycaemic unawareness. For such individuals the risk of staying on insulin may genuinely be higher than the risks associated with pancreas transplantation.
How successful are pancreas transplants?
Success after pancreas transplantation is defined as becoming independent of insulin. Approximately 85% of patients receiving simultaneous pancreas/kidney transplants will remain insulin independent one year after the transplant. Whilst problems can still occur and transplants can fail beyond one year, the long term success rate of pancreas transplantation is similar to the success rate of other organ transplants such as kidney, liver or heart transplants.
Are islet transplants not better and safer than pancreas transplants?
As mentioned before, the insulin producing cells comprise only about 2% of the pancreas. If these islets are separated from the remainder of the pancreas, they can be transplanted with a very simple procedure that does not require major surgery. Islet transplantation recipients also require immunosuppressive medication to prevent rejection. For a variety of reasons islet transplantation is not as effective as whole organ pancreas transplantation in offering insulin independence.
Islet transplantation is used for a different group of patients with type I diabetes with different indications. The most common indication for islet transplantation is severe hypoglycaemic unawareness. Type I diabetic patients suffering from this problem can be reliably cured of their hypoglycaemic unawareness with the simple procedure of islet transplantation however most of these patients continue to require insulin. They will almost always need less insulin and control of diabetes will be much easier.
Islet transplantation therefore is a complementary procedure to pancreas transplantation. It is used in a small number of patients for different indications and seldom produces long term insulin independence.
In the future research into stem cells and genetic engineering will undoubtedly help improve the success rate of islet transplantation and it will ultimately replace pancreas transplantation as a simpler and safer procedure. Exactly how long this will take to achieve is difficult to predict but it is certainly more than 10 and perhaps more than 20 years away.