2008 Clinical Practice Guidelines - Canadian Diabetes Association

2008 CLINICAL PRACTICE GUIDELINES
S88
Pancreas and Islet Transplantation
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
The initial draft of this chapter was prepared by Breay W. Paty MD FRCPC, Erin Keely MD FRCPC
and Charlotte McDonald MD FRCPC
KEY MESSAGES
• Pancreas transplant can result in prolonged insulin independence
and a possible reduction in the progression
of secondary complications of diabetes.
• Islet transplant can result in transient insulin independence
and can reliably stabilize blood glucose concentrations
in people with glycemic lability.
• The risks of chronic immunosuppression must be carefully
weighed against the potential benefits of pancreas
or islet transplant for each individual.
INTRODUCTION
Beta cell replacement as a means of restoring endogenous
insulin secretion, either by whole organ pancreas transplant
or islet transplant, has a number of potential advantages over
standard exogenous insulin therapy for the treatment of type
1 diabetes, including improved glycemic control and the
potential for insulin independence. However, any advantages
must be weighed against the risks and adverse effects of surgery
and chronic immunosuppressive therapy that accompany
these treatments. Unfortunately, the absence of data from
randomized controlled trials (RCTs) makes it difficult to
draw firm conclusions regarding the efficacy of these therapies
compared with intensive medical management of diabetes.
Nevertheless, some general recommendations can be
made regarding the role of pancreas and islet transplant in
the context of current clinical experience.
WHOLE PANCREAS TRANSPLANTATION
Pancreas transplantation has progressed significantly in terms
of surgical technique and immunosuppression since it was
first introduced in the 1960s (1). It is most commonly categorized
on the basis of the presence or absence of a kidney
transplant and the relative timing of the procedures: simultaneous
pancreas kidney (SPK) transplant; pancreas after
kidney (PAK) transplant; or pancreas transplant alone (PTA),
in the absence of a kidney transplant. Worldwide, noncontrolled
pancreas graft and patient survival rates differ
slightly among these 3 categories (2). However, in the
absence of large RCTs, it is unclear whether these differences
are clinically significant.
Metabolic studies demonstrate a marked improvement in
glycemic control and glycated hemoglobin (A1C) after suc-
cessful whole pancreas transplant, with most recipients
achieving insulin independence that can last for many years
(3,4). A reduction in albuminuria has been shown at 1 year
posttransplant (5). Similarly, improvements in the histologic
changes of diabetic nephropathy have been reported after 5
to 10 years posttransplant (6). Studies also show an improvement
and/or stabilization of diabetic retinopathy (7) after an
initial risk of worsening due to a rapid reduction in glycemia
(8). The benefits of pancreas transplant are less clear in
patients with advanced retinal disease (9). Peripheral sensory
and motor neuropathies have been shown to improve after
pancreas transplant (10,11). Improvements in autonomic
neuropathy are less consistent and may take longer to achieve
(12,13). There is growing evidence that pancreas transplant
improves cardiovascular (CV) function (14) and may reduce
cardiac events (15). However, studies have generally been
small and nonrandomized. It remains uncertain whether pancreas
transplant improves overall mortality rates (16).
Finally, diabetes-related quality of life appears to improve
after pancreas transplant, although overall quality of life may
not change (17).
ISLET TRANSPLANTATION
Islet transplantation is a less invasive procedure than pancreas
transplantation. It involves the infusion of islets isolated from
cadaveric pancreata via the portal vein into the liver (18).
Unlike whole pancreas transplant recipients, most islet transplant
recipients require at least 2 islet infusions to achieve
insulin independence, although there has been recent shortterm
success using single islet donors in some centres (19).
The rate of posttransplant insulin independence at the most
experienced centres is approximately 80% at 1 year, but
declines to about 10% at 5 years (20-22). Rates of insulin
independence may be lower at less experienced centres
(23,24). Most transplant recipients continue to have some
endogenous insulin secretion even after insulin independence
is lost. However, there are very few long-term data
regarding function of the transplanted islets after 5 years.
Most published studies involve islet transplant in the absence
of a kidney transplant (islet transplant alone [ITA]).There is
some evidence suggesting that islet transplant performed at
the same time as a kidney transplant (simultaneous islet kidney
[SIK]) or after a kidney transplant (islet after kidney
[IAK]) may have comparable results (25,26).