2 The procedure

2.1 Indications and current treatments

2.1.1 Type 1 diabetes mellitus is caused by insufficient insulin secretion and is treated with exogenous insulin. This may result in hypoglycaemic episodes, which are usually easily recognised and treated. In a few people, hypoglycaemia occurs without warning ('hypoglycaemia unawareness'), with life-threatening consequences.

2.2 Outline of the procedure

2.2.1 Islet cells are obtained from pancreata of brain-dead donors (two are often required). The patient is started on immunosuppressive therapy, which continues for the long term. 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.

Sections 2.3 and 2.4 describe efficacy and safety outcomes which were available in the published literature and which the Committee considered as part of the evidence about this procedure. For more details, refer to the Sources of evidence.

2.3 Efficacy

2.3.1 A registry study of 112 patients reported that a severe hypoglycaemic episode was experienced by 5% in the year following transplantation compared with 82% in the year prior to transplantation (numbers not reported). In a case series of 36 patients, there were no hypoglycaemic episodes among patients with residual graft function during follow-ups of 1–12 months. A case series of 65 patients reported significantly reduced hypoglycaemia unawareness and improved diabetic control compared with baseline for up to 4 years after transplantation (numbers not reported).

2.3.2 In the registry study of 112 patients, 67% and 58% were insulin independent at 6 months and 1 year after transplantation, respectively (numbers not reported). For patients who remained insulin dependent, insulin requirements were reduced by a mean of 57% from baseline at 6 months and 69% at 1 year. In this study, 13% (15/112) of patients had complete graft failure. In the case series of 36 patients, 58% (21/36) achieved insulin independence during a median follow-up of 41 months. However, 76% (16/21) were insulin dependent again after 2 years.

2.3.3 A non-randomised controlled trial of 99 patients who had the procedure reported that fear of hypoglycaemic episodes as measured by the 'Hypoglycaemia fear survey' improved significantly following the first infusion of islet cells (p < 0.00001).

2.3.4 The Specialist Advisers considered key efficacy outcomes to include reduction in hypoglycaemic episodes, improved glycaemic control, normalised C-peptide levels (indicating graft function) and insulin independence.

2.4 Safety

2.4.1 Two case series of 65 and 51 patients reported procedure-related intraperitoneal bleeding in 23% (15/65), and 8% (4/51; 7 haemorrhage episodes) of patients. A case series of 36 patients reported intraperitoneal bleeding during 9% (7/77) of infusions. Portal (or branch) vein thrombosis was reported in 8% (5/65), 4% (2/51) and 3% (2/36) of patients, and gall bladder puncture requiring laparotomy in 3% (2/65 and 1/36) of patients.

2.4.2 In the registry study of 112 patients, 77 serious adverse events were reported; 22% (17/77) were life-threatening and 58% (45/77) required hospitalisation. Overall, 95% (73/77) of adverse events resolved without residual effects. The authors judged that 17% of all adverse events were related to the infusion procedure and 27% to immunosuppression (numbers not reported).

2.4.3 A case report described a patient who died of West Nile virus encephalitis – a potential infection in immunosuppressed patients.

2.4.4 The Specialist Advisers considered theoretical adverse events to include haemorrhage, portal vein thrombosis, portal hypertension, immunosuppression-related complications and transmission of donor material containing infectious agents or neoplastic cells.

2.5 Other comments

2.5.1 The Committee noted that immunosuppressive regimens and technology for harvesting islet cells continue to evolve.

2.5.2 The Committee noted that the National Commissioning Group (NCG), which has a remit to commission highly specialised national services for very rare conditions or treatments for the population of England, has developed service standards for pancreatic islet cell transplantation that are used as the basis for designation and commissioning of these services. Scottish residents also have access to the service under an agreement between the NCG and the National Services Division, Scotland. Health Commission Wales has a separate agreement with the provider for Welsh residents. The Regional Medical Services Consortium (RMSC) commissions specialist regional services for the population of Northern Ireland. The RMSC will commission outside the region, on an individual basis, in cases for which services are not available in Northern Ireland.