The field of organ transplantation has expanded significantly over the last decade but whilst transplantation for complications of diabetes (including renal transplants) are well established, treating the underlying issue in Type 1 diabetes – specifically the loss of pancreatic islets has been a problem. Whole pancreas transplants, usually performed as a combined kidney/ pancreas transplant have been an option for some time. However, it is associated with significant complications on top of rejection; including pancreatitis and issues with the exocrine function of the pancreas especially as only the islets are required. Transplantation of the islets themselves has proven difficult due to issues separating them from the pancreas and the choice of immunosuppressive agent – the use of corticosteroids being a major problem. In 2000 however, the publication of a study of 7 patients who had achieved euglycaemia using a steroid free protocol (of Sirolimus, Tacrolimus and Daclizumab) – the Edmonton regime – has significantly changed the outlook.
In order to obtain sufficient islets, up to 2 donor pancreas are required to provide the 1 million islets which are released via purified collagenases. Under local anaesthesia (sometimes with sedation) and using imaging guidance, a catheter is inserted percutaneously into the portal vein and the grafted islet cells infused into the liver. More than one infusion may be required following which lifelong immunosuppression is required.
Whilst the concept of islet transplantation may seem a panacea to patients, the shortage of donors and need for long term immunosuppression are major blocks, hence guidance from NICE regarding suitability (essentially those patients who are difficult to control often due to severe hypos despite education, pumps therapy etc.). Furthermore, an islet transplant does not automatically result in freedom from insulin. A variety of studies, usually registry or case series, have shown that insulin independence is achieved in 24-85% of patients up to 2 years following transplant. More importantly however, the incidence of severe hypoglycaemia was significantly reduced (a registry study showed a reduction in severe hypos from 82% to 4.5%) – a major improvement in quality of life.
In the UK, there are 7 centres performing these transplants with referral criteria being >2 severe hypos in the last year and impaired awareness of hypoglycaemia as well as patients who have already received a renal transplant experiencing issues with hypoglycaemia.
Although the rapid development and increasing sophistication of glucose sensing and insulin delivery devices the ultimate goal of a closed loop system may eventually reduce the need for transplants, they still have a place for a small number of patients.
Dr Mark Freeman
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