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The Tom Mandel Islet Transplant Program

The Tom Mandel Islet Transplant Program was established in 2004 on the St Vincent’s Hospital campus in Melbourne, by a multidisciplinary team of scientists and clinicians. The Program is now an integral part of the Australian Islet Transplant Consortium, delivering improved clinical outcomes for patients with type 1 diabetes with severe hypoglycemia unawareness and in whom insulin therapy has failed.

Islet transplant recipients have improved glycemic control and quality of life and, in many cases, no longer require insulin injections.

This page provides information for people who want to know more about the Islet Transplant Program at St Vincent’s Hospital.

Please get in contact with our Clinical Nurse Coordinator, Ms Kathy Howe (ph (03) 92313678, email kathy.howe@svha.org.au) if you would like further information.

What is Islet Transplantation?

Islet transplantation is a treatment for people who have unstable type 1 diabetes. It has been available in Australia since 2006. The procedure involves isolating insulin-producing islet cells from the pancreas of a deceased organ donor and infusing these cells into the recipient, via the portal vein of the liver.

Our work and overseas studies have shown that this procedure eliminates or reduces dangerous low blood sugar episodes (hypoglycemia) and helps reverse hypoglycaemia unawareness in more than 90% of patients who have an islet transplant (Clinical Islet Transplant Registry, eighth annual report). In more than 50% of recipients, islet transplantation restores normal blood sugar levels without the need for insulin injections for several years. There are indications that quality of life may also be improved post-transplantation as assessed by an increased ability to work and driving a car but this requires further assessment. Risks of islet transplantation include risks associated with the surgical procedure and side effects from the immunosuppressive drugs that transplant recipients must take to stop the immune system from rejecting the transplanted islets.  

The Tom Mandel Islet Transplant Program in Melbourne is part of the Australian Islet Transplant Consortium offering national access to islet transplantation. We provide access to the procedure for people from Victoria and Tasmania, while Sydney’s Westmead Hospital services recipients living in NSW, ACT, Qld and WA, and the Royal Adelaide Hospital, those living in SA and NT. The availability of these services is flexible; for example, a Tasmanian recipient had a transplant in Adelaide instead of Melbourne because they had family in Adelaide. The Consortium is able to provide these services with funds from the Nationally Funded Centre Program.

At St Vincent’s Hospital Melbourne (SVHM), the senior staff on the campus responsible for delivery of the Tom Mandel Islet Transplant Program are:

  • Professor Richard MacIssac, Director of Department of Endocrinology and Diabetes
  • Associate Prof David Goodman Transplant Physician & Nephrologist Department of Nephrology
  • Professor Thomas Kay, Director of St Vincent’s Institute of Medical Research (SVI)
  • Ms Jacqueline Bilo, General Manager Medicine and Emergency Services

Other key staff involved in the Program include the islet transplant clinical nurse coordinator (Ms Kathy Howe, SVHM) and the islet isolation manager (Dr Tom Loudovaris, SVI).

Eligibility

To be eligible for the program, the recipient must:

  • Be aged between 18-70 years old
  • Have had type 1 diabetes for more than 5 years
  • Have unstable blood glucose levels including severe and frequent hypoglycaemic episodes  OR
  • Have lack of awareness of hypoglycaemia (with blood sugar levels <2.9) indicated by more than two episodes of severe hypoglycaemia requiring third party assistance or more than two episodes of DKA in the last year OR
  • Have progressive complications
  • Have failed intensive insulin therapy (e.g. three injections/d or insulin pump) with testing four times/day, monitored by an endocrinologist or primary carer
  • Be capable of understanding the procedure and its risks, and able to provide informed consent.  

People are not eligible for the program if they have the following:

  • Established nephropathy macro-albuminuria (albumin >300 mg/day)
  • Untreated proliferative retinopathy
  • Untreated/active cardiac disease including recent AMI
  • Chronic infections e.g. HIV, TB, Hep B or C
  • Cancer (except treated skin SCC or BCC)
  • Psychiatric disorder/substance abuse/history of or anticipated non-compliance
  • Pregnancy, intention to become pregnant, or failure to follow a medically reliable method of preventing conception, breastfeeding.
  • BMI > 27 kg/m2 or body weight > 90 kg

If you or your patient satisfies the eligibility criteria and you are interested in the transplant procedure, you should contact our Clinical Nurse Coordinator Ms Kathy Howe, phone (03) 92313678, email kathy.howe@svha.org.au

The Procedure

The procedure involves three steps: assessment/screening, the transplant procedure, and follow-up.

Recipient assessment and screening
The assessment phase is an opportunity for potential recipients to be provided with information and to ask questions so that they fully understand the procedure, its requirements, their suitability and the preparation they will need to undergo. They will also have the chance to meet some of the members of the islet transplant team.

During the initial visit, a detailed history is taken, which includes time of diagnosis, treatment, relevant past history, any diabetes-related complications and details about weekly hypoglycaemic episodes. If the subject fits the general criteria and is interested in proceeding, their suitability will be evaluated in a screening process.

If suitable for a transplant, the potential recipient will commence a general workup that includes taking of blood, chest x-ray, abdominal ultrasound and exercise stress test. They will also be screened for diabetes-related complications, which involves an eye examination, kidney function test and testing for possible infections and gastrointestinal tract complications. Their blood will be screened for antibodies that may increase the risk for rejection of the donor islet cells. The potential recipient’s tissue type is also identified so it can be compared with the donor's type.

At the following visit, 1-2 months later, the potential recipient will be required to keep a detailed logbook of their blood glucose levels, food intake, exercise duration and hypoglycaemic episodes. The logbook must be descriptive, outlining the content of the meals, the length of time spent exercising, and any possible illness. The potential recipient needs to record whether each hypoglycaemic episode was symptomatic or asymptomatic, how it was treated, the time it took place and whether support was required. During this time, the potential recipient will have regular phone contact with the islet transplant team to assess how they are managing.

This preparation period gives the potential recipient time to closely think about what the islet transplant involves and consider the various possible outcomes. It is recommended that potential recipients discuss the procedure with members of their family as it is important that they also understand what the recipient is about to undertake - a close support network is ideal. Family members are encouraged to attend the consultation.

The transplant procedure
Once recipients are enrolled in the program, the wait for suitable islet cells begins. It may take between 6 months and 2 years before a suitable islet cell preparation becomes available. During the wait, potential recipients must ensure that they are contactable at all times. Currently, to become insulin independent, the majority of people require two transplants, performed as two separate procedures. This means at least two donated organs are required for each recipient.

When a donation becomes available, the recipient prepares for the procedure. Sophisticated techniques are used to isolate the islets from the rest of the pancreatic tissue and to maximise the quality and quantity of islets available for transplantation.

The procedure is performed under local anaesthetic with mild sedation. A catheter is placed into the main vein of the liver, called the portal vein, after which the islet cells are infused. In Melbourne, this procedure is minimally invasive - the catheter is introduced through the skin and guided into the vein by a radiologist in the x-ray department. In Adelaide and Sydney, a surgeon makes a small incision and visualises the vein to place the catheter, a radiologist then guides the catheter into the liver. Once infused, the islets attach to small blood vessels in the liver and begin to make and release insulin. After the procedure, a small plug is inserted into the track left by the catheter to stop bleeding. A combination of immunosuppressive drugs is required to keep the immune system from destroying the transplanted islets.

After the procedure, the recipient is carefully monitored. There are some risks associated with the transplant, including bleeding from the liver (frequency of 0.6%), which may require a blood transfusion or, uncommonly, an operation to stop the bleeding. In addition, a clot can form in the portal vein or there can be increased blood pressure in the vein after the islet infusion. Worldwide experience (Clinical Islet Transplant Registry 2014 annual report) is that the majority of procedural adverse events are quickly resolved, with all being eventually resolved. All possible complications associated with the procedure are discussed in detail with the patient well before the transplant.

Follow-up
After the islet transplant, recipients are required to take immunosuppressive medication to ensure the survival of the newly infused islet cells. As with all types of transplants, without immunosuppressive medication the patient's body will reject the foreign cells. This means the medication has to be taken as long as the islets are functioning. Even with the medication, rejection can still happen and can occur at any stage after the procedure. This is why monitoring the blood glucose levels is important. Initially after the transplant, recipients still require insulin and care is taken to ensure the islet cells are not overworked. Over time, the doses are changed and adjusted. This stage is called ‘engrafting’.

While taking immunosuppressive medication to protect the islet cells, the body's immune system is quite vulnerable. Recipients have to be cautious to avoid any infections and need to be aware of the range of risks and side-effects associated with this medication.

Ongoing research

As well as performing successful islet cell transplants, our clinicians and scientists at SVI and SVHM are also working on ways to make the procedure safer and more effective. For example, we are part of a new Consortium effort developing novel tolerance protocols for islet transplantation using new reagents and drugs (funded by a JDRF Clinical Research Network). The clinical Transplant Program also provides a valuable opportunity for clinical research on human islets obtained but insufficient or not suitable for transplant. In the future, this program will provide a platform for future innovations in beta-cell replacement for type 1 diabetes, e.g. pig islet cells and encapsulation of islet cells.

Key Scientific Publications

  1. Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM and Rajotte RV. Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen.N Engl J Med 2000; 343(4): 230-8.
  2. Ryan EA, Lakey JRT, Rajotte RV, Korbutt GS, Kin T, Imes S, Rabinovitch A, Elliott JF, Bigam D, Kneteman NM, Warnock GL, Larsen I and Shapiro AMJ. Clinical Outcomes and Insulin Secretion After Islet Transplantation with the Edmonton Protocol. Diabetes 2001; 50:710-719.
  3. Ryan EA, Lakey JRT, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte RV and Shapiro AMJ. Successful Islet Transplantation: Continued Insulin Reserve Provides Long-Term Glycemic Control.Diabetes 2002; 51(7): 2148-57.
  4. Ryan EA, Paty BW, Senior PA, Shapiro AMJ. Risks and Side Effects of Islet Transplantation.Curr Diab Rep 2004; 4:304-309.
  5. Ryan EA, Shandro T, Green K, Paty BW, Bigam D, Shapiro AMJ, Vantyghem MC. Assessment of the Severity of Hypoglycemia and Glycemic Lability in Type 1 Diabetic Subjects Undergoing Islet Transplantation.Diabetes 2004; 53:955-962. Ryan EA, Paty BW, Senior PA, Lakey JRT, Bigam D, Al-Fadhli E, Shapiro AMJ.Beta-Score: An Assessment of Beta-Cell Function After Islet Transplantation.Diabetes Care 2005; 28: 343-347.
  6. Ryan EA, Paty BW, Senior PA, Bigam D, Al-Fadhli E, Kneteman NM, Lakey JRT, Shapiro AMJ. Five-Year Follow-Up After Clinical Islet Transplantation. Diabetes 2005; 54:2060-2069.
  7. Paty BW, Senior PA, Lakey JFRT, Shapiro AMJ, Ryan EA. Assessment of Glycemic Control After Islet Transplantation Using the Continuous Glucose Monitor in insulin-Independent Versus Insulin-Requiring Type 1 Diabetes Subjects. Diabetes Technol Ther 2006;8(2):165-172.
  8. Senior PA, Zeman M, Paty BW, Ryan EA, Shapiro AM. Changes in Renal Function after Clinical Islet Transplantation: Four-year Observational Study. Am J Transplant 2007;7(1):91-8.
  9. O'Connell, P. J., Holmes-Walker, D. J., Goodman, D., Hawthorne, W. J., Loudovaris, T., Gunton, J. E., Thomas, H. E., Grey, S. T., Drogemuller, C. J., Ward, G. M., Torpy, D. J., Coates, P. T., Kay, T. W., On behalf of the Australian Islet Transplant Consortium. Multicenter Australian Trial of Islet Transplantation: Improving Accessibility and Outcomes. American Journal of Transplantation, 13 (7) 1600-6143, 2013
  10. Marathe, C. S., Drogemuller, C. J., Marathe, J. A., Loudavaris, T., Hawthorne, W. J., O'Connell, P. J., Radford, T., Kay, T. W. H., Horowitz, M., Coates, P. T. and Torpy, D. J. (2015). "Islet Cell Transplantation in Australia: Screening, Remote Transplantation, and Incretin Hormone Secretion in Insulin Independent Patients". Hormone and Metabolic Research, 1 (47): 16-23

Contact

For more information about islet transplant program, please contact our Clinical Nurse Coordinator:
Ms Kathy Howe
P: (03) 92313678
E: kathy.howe@svha.org.au