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Pancreas transplant for diabetes mellitus

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ABSTRACTPancreas transplant is an option for patients with type 1 diabetes and for some patients with type 2 diabetes and advanced diabetic kidney disease. The procedure has a high success rate, and performing it earlier in the course of diabetes could help prevent or reverse the long-term complications of diabetes.

KEY POINTS

  • Current options are simultaneous pancreas-kidney transplant, pancreas-after-kidney transplant, and pancreas-alone transplant.
  • Simultaneous pancreas-kidney transplant provides a significant survival benefit over insulin- and dialysis-based therapies.
  • Isolated pancreas transplant for diabetic patients without uremia can prevent hypoglycemic unawareness.


 

References

Pancreas transplant is the only long-term diabetes treatment that consistently results in normal hemoglobin A1c levels without the risk of severe hypoglycemia. Additionally, pancreas transplant may prevent, halt, or even reverse the complications of diabetes.

Here, we explore the indications, options, and outcomes of pancreas transplant as a treatment for diabetes mellitus.

DIABETES IS COMMON, AND OFTEN NOT WELL CONTROLLED

Diabetes mellitus affects more than 25 million people in the United States (8.3% of the population) and is the leading cause of kidney failure, nontraumatic lower-limb amputation, and adult-onset blindness. In 2007, nearly $116 billion was spent on diabetes treatment, not counting another $58 billion in indirect costs such as disability, work loss, and premature death.1

Only about half of patients achieve hemoglobin A1c < 7% with medical therapy

Despite the tremendous expenditure in human, material, and financial resources, only about 50% of patients achieve their diabetes treatment goals. In 2013, a large US population-based study­2 reported that 52.2% of patients were achieving the American Diabetes Association treatment goal of hemoglobin A1c lower than 7%. A similar study in South Korea3 found that 45.6% were at this goal.

Most of the patients in these studies had type 2 diabetes, and the data suggested that attaining glycemic goals is more difficult in insulin-treated patients. Studies of patients with type 1 diabetes found hemoglobin A1c levels lower than 7% in only 8.1% of hospitalized patients with type 1 diabetes, and in only 13% in an outpatient diabetes clinic.4,5

YET RATES OF PANCREAS TRANSPLANT ARE DECLINING

Pancreas transplant was first performed more than 40 years ago at the University of Minnesota.6 Since then, dramatic changes in immunosuppression, organ preservation, surgical technique, and donor and recipient selection have brought about significant progress.

Currently, more than 13,000 patients are alive with a functioning pancreas allograft. After reaching a peak in 2004, the annual number of pancreas transplants performed in the United States has declined steadily, whereas the procedure continues to increase in popularity outside North America.7 The primary reason for the decline is recognition of donor factors that lead to success—surgeons are refusing to transplant organs they might have accepted previously, because experience suggests they would yield poor results. In the United States, 1,043 pancreas transplants were performed in 2012, and more than 3,100 patients were on the waiting list.8

Islet cell transplant—a different procedure involving harvesting, encapsulating, and implanting insulin-producing beta cells—has not gained widespread application due to very low long-term success rates.

THREE CATEGORIES OF PANCREAS TRANSPLANT

Pancreas transplant facts and figures, 2012

Pancreas transplant can be categorized according to whether the patient is also receiving or has already received a kidney graft (Table 1).

Simultaneous kidney and pancreas transplant is performed in patients who have type 1 diabetes with advanced chronic kidney disease due to diabetic nephropathy. This remains the most commonly performed type, accounting for 79% of all pancreas transplants in 2012.8

Pancreas-after-kidney transplant is most often done after a living-donor kidney transplant. This procedure accounted for most of the increase in pancreas transplants during the first decade of the 2000s. However, the number of these procedures has steadily decreased since 2004, and in 2012 accounted for only 12% of pancreas transplants.8

Pancreas transplant alone is performed in nonuremic diabetic patients who have labile blood sugar control. Performed in patients with preserved renal function but severe complications of “brittle” diabetes, such as hypoglycemic unawareness, this type accounts for 8% of pancreas transplants.9

Indications for pancreas transplant

A small number of these procedures are done for indications unrelated to diabetes mellitus. In most of these cases, the pancreas is transplanted as part of a multivisceral transplant to facilitate the technical (surgical) aspect of the procedure—the pancreas, liver, stomach, gallbladder, and part of the intestines are transplanted en bloc to maintain the native vasculature. Very infrequently, pancreas transplant is done to replace exocrine pancreatic function.

A small, select group of patients with type 2 diabetes and low body mass index (BMI) may be eligible for pancreas transplant, and they accounted for 8.2% of active candidates in 2012.8 However, most pancreas transplants are performed in patients with type 1 diabetes.

WHAT MAKES A GOOD ALLOGRAFT?

Pancreas allografts are procured as whole organs from brain-dead organ donors. Relatively few pancreas allografts (3.1% in 2012) are from cardiac-death donors, because of concern about warm ischemic injury during the period of circulatory arrest.8

Preparing and implanting the graft

Figure 1.

Proper donor selection is critical to the success of pancreas transplant, as donor factors including medical history, age, BMI, and cause of death can significantly affect the outcome. In general, transplant of a pancreas allograft from a young donor (age < 30) with excellent organ function, low BMI, and traumatic cause of death provides the best chance of success.

The Pancreas Donor Risk Index (PDRI)10 was developed after analysis of objective donor criteria, transplant type, and ischemic time in grafts transplanted between 2000 and 2006. One-year graft survival was directly related to the PDRI and ranged between 77% and 87% in recipients of “standard” pancreas allografts (PDRI score of 1.0). Use of grafts from the highest (worst) three quintiles of PDRI (PDRI score > 1.16) was associated with 1-year graft survival rates of 67% to 82%, significantly inferior to that seen with “higher- quality” grafts, again emphasizing the need for rigorous donor selection.10

In addition to these objective measures, visual assessment of pancreas quality at the time of procurement remains an equally important predictor of success. Determination of subjective features, such as fatty infiltration and glandular fibrosis, requires surgical experience developed over several years. In a 2010 analysis, dissatisfaction with the quality of the donor graft on inspection accounted for more than 80% of refusals of potential pancreas donors.11 These studies illustrate an ill-defined aspect of pancreas transplant, ie, even when the pancreas donor is perceived to be suitable, the outcome may be markedly different.

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