Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d’endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie – dialyse – transplantation (SFNDT)

Abstract

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Advances in β-cell replacement therapy for the treatment of type 1 diabetes

“…Pancreas transplantation alone or pancreas-afterkidney transplantation can also be considered in patients aged up to 55 years without cardiovascular morbidity. 23 The stages of islet transplantation…”

“…In recipients combining all these favourable factors, 5year transplant survival was 69% and 5-year insulin independence was 47%, both approaching the proportions reported after pancreas transplantation alone. 23 Islet transplantation in patients with type 1 diabetes triggers immune reactions that are innate and specific, autoimmune and alloimmune, as well as humoral or cellular. 67 Donor-specific antibodies are frequently detected in patients with poor transplant survival, and have been associated with HLA-DR mismatches and pre-existing panel-reactive antibodies.…”

Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies

“…Pancreas or islet transplantation may be considered for patients with type 1 diabetes who require kidney transplantation or who have 'brittle' forms of type 1 diabetes characterised by labile glycaemic control and recurrent severe hypoglycaemia despite optimal medical therapy [6]. While protocols differ by institution, 'brittle' (labile) type 1 diabetes is often defined by ≥1 episode of severe hypoglycaemia per year, with hypoglycaemic unawareness, as assessed by a standardised instrument, such as the Clarke scale [2].…”

“…When either therapy is an option, patient characteristics and patient goals dictate selection of the procedure [6]. Islet transplant carries a lower risk for surgical morbidity and complications and is highly successful at eliminating severe hypoglycaemia and glucose lability.…”

Pancreas-on-a-Chip Technology for Transplantation Applications

“…Beta cell replacement therapy in the form of both pancreas transplantation and allogeneic islet transplantation has proven to be a safe alternative treatment to external insulin administration, offering more precise control over blood glucose, reducing incidents of unaware hypoglycemia, and improving quality of life in patients with T1D [3]. The indications for beta cell therapy and factors influencing the chosen strategy are not covered by this review and can be read elsewhere [4]. For pancreas and islet transplantations, the procurement of the donor organ is an essential upstream step for the success of the islet isolation procedure and for graft survival [5].…”