Authors' objectives:

This review aims to assess the effectiveness and cost-effectiveness of islet transplantation in non-uremic patients with type 1 diabetes mellitus (DM).

Authors' results and conclusions: A health technology assessment from Alberta in 2002 stated that limited evidence from the Edmonton series suggested that islet transplantation (using the Edmonton Protocol) is effective in 1) controlling labile diabetes and 2) protecting against unrecognized hypoglycemia in highly selected patients in the short term. This conclusion was based on the results of 11/17 insulin independent patients who were followed up for a median of 20.4 months in a trial. In contrast, another author and also a member of the Edmonton team concluded that glucagon and epinephrine responses and hypoglycemic symptom recognition were not improved by islet transplantation in patients receiving the procedure in Edmonton, despite prolonged insulin independence and near-normal glycemic control. The latter study examined seven islet recipients, seven type 1 DM patients (nonislet recipients), and seven nondiabetic control patients. The follow-up for most studies was short. It was suggested that the modifications to the conventional islet transplantation approaches, including the steroid free immunosuppressive regimen, islet preparation in xenoproteins free media and transplantation of fresh islets from multiple donors were associated with the success. The effects of islet transplantation on beta cell function (secretion of insulin) look promising, however, the effects of islet transplantation on pancreatic alpha cell function (secretion of counterregulatory hormones such as glucagon and epinephrine) in long standing type 1 diabetes remain unclear. The most important barriers to more widespread islet transplantation using the Edmonton protocol are the availability of sufficient donor organs and the uncertainty of long term steroid free immunosuppressive therapy. Because the number of cadaveric pancreas donors is inadequate to the treat the increasing numbers of individuals on organ transplant waiting lists, isolated islet transplantation is unlikely to become practical for treatment of diabetes if each recipient requires islets from several (two to four) donors. Therefore, it is important that the experience of the Edmonton investigators be validated by other centres not only in terms of effectiveness of the new immunosuppressive protocol, but also in the need for multiple transplants. Preliminary results from a multinational trial indicate wide variation in the success of islet transplantation between different sites. This raises concern about the reproducibility of the results.

Authors' recommendations: The current evidence on the use of islet transplantation for nonuremic type 1 diabetic patients is limited since it is based on studies with weak methodological design. The assessment of islet transplantation is based on several small case series studies or small clinical studies. The results from these studies were mixed since the objectives and the protocols differed at each centre. In particular, many jurisdictions have, to date, been unable to reproduce results achieved in Edmonton (success rate of 23 per cent versus 90 per cent) - this is the focus of an ongoing multicentre study. One trial reported that the median follow-up time for the 17 patients undergoing the Edmonton Protocol was 20.4 months from the first transplant. As of January, 2002, 11/17 patients remained insulin independent. Three of the 11 insulin independent patients had negative C-peptide secretion, indicative of impaired islet function. The effect of islet transplantation on restoring hormonal responses to hypoglycemia is inconclusive. Islet transplantation in nonuremic type 1 diabetic patients with hypoglycemia unawareness or uncontrolled diabetes is an evolving procedure with promising preliminary, but inconclusive final results.

Authors' methods: Systematic review

Project Status: Completed

Year Published: 2003

URL for published report: http://www.health.gov.on.ca/english/providers/program/mas/tech/reviews/pdf/rev_islettrans_100103.pdf

URL for additional information: http://www.hqontario.ca/evidence/publications-and-ohtac-recommendations/ohtas-reports-and-ohtac-recommendations/islet-transplantation

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Medical Advisory Secretariat

Contact Address: Medical Advisory Secretariat, 20 Dundas Street West, 10th Floor, Toronto, ON M5G 2N6 CANADA. Tel: 416-314-1092l; Fax: 416-325-2364;

Contact Name: MASinfo.moh@ontario.ca

Contact Email: MASinfo.moh@ontario.ca

Copyright: Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care