Chapter 20: Pancreas and Islet Transplantation

Restoring endogenous insulin secretion by whole pancreas or islet transplantation is an alternative to insulin injection therapy in select individuals with type 1 diabetes.
Nonrandomized studies demonstrate that both pancreas and islet transplantation can result in insulin independence and glucose stability, especially in the setting of glucose liability or frequent, severe hypoglycemia.

Pancreas transplantation can result in complete independence from exogenous insulin in many cases.
Mean pancreas graft and patient survival rates differ among the 3 major types of transplantations. Long-term pancreas graft survival declines with time.
Glycemic control and glycated hemoglobin (A1C) are markedly improved after successful pancreas transplantation, with most recipients achieving normal glucose tolerance, although with hyperinsulinemia.
A reduction in albuminuria has been noted at 1 year, and improvements in the histological changes associated with diabetic nephropathy have been reported 5 to 10 years post transplantation.
Individuals with type 1 diabetes and end stage renal disease (ESRD) who are being considered for kidney transplantation should also be considered for simultaneous pancreas transplantation [Grade D, Level 4].
- Whether successful simultaneous pancreas kidney (SPK) transplantation improves renal graft survival is unclear.
- The impact of pancreas transplantation on overall patient survival is also uncertain.
- Peripheral sensory and motor neuropathies have been shown to improve after pancreas transplantation but these findings are not consistent and may take years to achieve.
- Diabetes-related quality of life (QOL) appears to improve after pancreas transplantation
- For more detail from research studies please refer to the the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 20.

Islet allotransplantation

Islet allotransplantation involves the infusion of islets isolated from cadaveric pancreata via the portal vein into the liver, either alone or in association with a renal transplantation.
Individuals with type 1 diabetes with preserved renal function, or who have undergone successful kidney transplantation but have persistent metabolic instability characterized by severe glycemic lability and/or severe hypoglycemia despite best efforts to optimize glycemic control, may be considered for pancreas or islet allotransplantation [Grade D, Consensus].
Successful islet transplantation can result in stable, near-normal glycemic control (A1C, glycemic variability) with a reduction or elimination of hypoglycemia over and above what can be achieved with insulin injections or even insulin pump therapy.
Insulin independence can be achieved in most recipients but often requires 2 or more transplantation procedures. However, patients who are not able to maintain insulin independence may still benefit from more stable blood glucose control that results from ongoing graft function.
Small, short-term studies also suggest stabilization of retinopathy and neuropathy with islet allotransplantation.
Successful islet transplantation can improve QOL by reducing the fear of hypoglycemia but can be negatively impacted by adverse effects from immunosuppressive agents.

Islet autotransplantation

Individuals undergoing total pancreatectomy for benign pancreatic disease may be considered for islet autotransplantation but only in the context of an experienced islet transplantation centre [Grade D, Consensus].
In islet autotransplantation, islets are isolated from an individual's own resected pancreas following pancreatectomy for benign pancreatic disease (e.g. chronic, painful pancreatitis).
Even if insulin independence is not achieved, islet autotransplantation may result in reduced exogenous insulin requirements and a lower risk of hypoglycemia.
As a result, the ratio of benefit to risk of this procedure may exceed that noted with islet allotransplantation.

Pancreas transplantation is associated with significant perioperative risks, including graft thrombosis, hemorrhage, pancreatitis, wound infection, peripancreatic abscesses and duodenal stump leakage.
Islet transplantation is associated with fewer procedural risks, which may include intraperitoneal hemorrhage, partial portal vein thrombosis or gallbladder puncture.
These complications occur in <10% of procedures and usually are self-limited.
Both pancreas and islet transplantations require long-term immunosuppression, which is associated with a number of risks and side effects (though usually mild).

**Table 1: Reported graft survival rates according to type of pancreas transplantation**
Transplantation type	1 Year	5 Years	10 Years	15 Years
SPK	83%	69%	51%	33%
PAK	74%	45%	24%	13%
PTA	78%	54%	28%	9%
SPK, simultaneous pancreas kidney; PAK, pancreas after kidney; PTA, pancreas transplant alone.

**Table 2: Comparison of beta cell replacement modalities**
	Islet	Pancreas
Outcomes
Reduce or eliminate hypoglycemia	Yes	Yes
Improve A1C	Yes	Yes
Insulin independence	Yes*	Yes
Effect on diabetes-related complications
Microvascular	May be stabilized^†	Improved
Macrovascular	Not known	May be improved
Risks
Procedural risks	Minor procedural risk	Major surgical risk
Immunosuppression	Similar agents,^‡ life-long immunosuppression
Other Considerations
ESRD	Avoid	Consider SPK
Functioning renal transplant	Consider IAK if glycemic lability or hypoglycemia^§	Consider PAK if glycemic lability or hypoglycemia^§
A1C, glycated hemoglobin; ESRD, end stage renal disease; IAK, islet after kidney; PAK, pancreas after kidney; SPK, simultaneous pancreas kidney. ∗ More than 1 islet infusion may be required. † Retinopathy and neuropathy may be stabilized. ‡ Steroids are avoided in islet transplantation but may be used in whole pancreas transplantation. § No additional risk from immunosuppression

For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 20.