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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 20: Pancreas and Islet Transplantation

Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

Introduction
  • 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
  • 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.

TABLE 1

Islet Transplantation

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.
Risks Associated with Pancreas and Islet Transplantation
  • 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 2

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.