Pancreas transplant for diabetes mellitus

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Pancreas transplant for diabetes mellitus
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Hannah R. Kerr, MD
Betul Hatipoglu, MD
Venkatesh Krishnamurthi, MD

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.

 

 

SURGICAL COMPLICATIONS

Surgical complications have long been considered a limiting factor in the growth of pancreas transplant. Technical failure or loss of the graft within 90 days is most commonly due to graft thrombosis, leakage of the enteric anastomosis, or severe peripancreatic infection. The rate of technical failure has declined across all recipient categories and is currently about 9%.8

DO RECIPIENT FACTORS AFFECT OUTCOMES?

As mentioned above, the PDRI identifies donor factors that influence the 1-year graft survival rate. Recipient factors are also thought to play a role, although the influence of these factors has not been consistently demonstrated.

Humar et al15 found that recipient obesity (defined in this study as BMI > 25 kg/m2) and donor age over 40 were risk factors for early laparotomy after pancreas transplant.15 Moreover, patients undergoing early laparotomy had poorer graft survival outcomes.

This finding was reinforced by an analysis of 5,725 primary simultaneous pancreas-kidney recipients between 2000 and 2007. Obesity (BMI 30 ≥ kg/m2) was associated with increased rates of patient death, pancreas graft loss, and kidney graft loss at 3 years.16

More recently, Finger et al17 did not find a statistically significant association between recipient BMI and technical failure, but they did notice a trend toward increased graft loss with a BMI greater than 25 kg/m2. Similarly, others have not found a clear adverse association between recipient BMI and pancreas graft survival.

Intuitively, obesity and other recipient factors such as age, vascular disease, duration of diabetes, and dialysis should influence pancreas graft survival but have not been shown in analyses to carry an adverse effect.18 The inability to consistently find adverse effects of recipient characteristics is most likely due to the relative similarity between the vast majority of pancreas transplant recipients and the relatively small numbers of adverse events. In 98 consecutive pancreas transplants at our center between 2009 and 2014, the technical loss rate was 1.8% (unpublished data).

Acute rejection most commonly occurs during the first year and is usually reversible. More than 1 year after transplant, graft loss is due to chronic rejection, and death is usually from underlying cardiovascular disease.

The immunosuppressive regimens used in pancreas transplant are similar to those in kidney transplant. Since the pancreas is considered to be more immunogenic than other organs, most centers employ a strategy of induction immunosuppression with T-cell–depleting or interleukin 2-receptor antibodies. Maintenance immunosuppression consists of a calcineurin inhibitor (tacrolimus or cyclosporine), an antimetabolite (mycophenolate), and a corticosteroid.8

Immunosuppressive complications occur at a rate similar to that seen in other solid-organ transplants and include an increased risk of opportunistic infection and malignancy. The risk of these complications must be balanced against the patient’s risk of health decline with dialysis and insulin-based therapies.

OVERALL OUTCOMES ARE GOOD

The success rate of pancreas transplant is currently at its highest since the inception of the procedure. The unadjusted patient survival rate for all groups is over 96% at 1 year, and over 80% at 5 years.8 One-year patient survival after pancreas transplant alone, at better than 96%, is the highest of all organ transplant procedures.9

Patient survival 1 year after pancreas-alone transplant is > 96%

Several recently published single-center reviews of pancreas transplant since 2000 report patient survival rates of 96% to 100% at 1 year and 88% to 100% at 5 years.19–22 This variability is likely closely linked to donor and recipient selection, as centers performing smaller numbers of transplants tend to be more selective and, in turn, report higher patient survival rates.19,21

Long-term patient survival outcomes can be gathered from larger, registry-based reviews, accepting limitations in assessing causes of patient death. Siskind et al23 analyzed the outcomes of 20,854 US pancreas transplants done between 1996 and 2012 and found the 10-year patient survival rate ranged from 43% to 77% and was highly dependent on patient age at the time of the procedure.23 Patient survival after transplant must be balanced against the generally poor long-term survival prospects of diabetic patients on dialysis.

By type of transplant, pancreas graft survival rates at 1 year are 89% for simultaneous pancreas-kidney transplant, 86% for pancreas-after-kidney transplant, and 84% for pancreas-alone transplant. Graft survival rates at 5 years are 71% for simultaneous pancreas-kidney transplant, 65% for pancreas-after-kidney transplant, and 58% for pancreas-alone transplant.8,9

Simultaneous pancreas-kidney transplant has been shown to improve the survival rate compared with cadaveric kidney transplant alone in patients with type 1 diabetes and chronic kidney disease.24,25 The survival benefit of isolated pancreas transplant (after kidney transplant and alone) is not evident at 4-year follow-up compared with patients on the waiting list. However, the benefit for the individual patient must be considered by weighing the incapacities experienced with insulin-based treatments against the risks of surgery and immunosuppression.26,27 For patients who have experienced frequent and significant hypoglycemic episodes, particularly those requiring third-party assistance, pancreas transplant can be a lifesaving procedure.

Effects on secondary diabetic complications

Notwithstanding the effect on the patient’s life span, data from several studies of long-term pancreas transplant recipients suggest that secondary diabetic complications can be halted or even improved. Most of these studies examined the effect of restoring euglycemia in nephropathy and the subsequent influence on renal function.

Effect on renal function. Kleinclauss et al28 examined renal allograft function in type 1 diabetic recipients of living-donor kidney transplants. Comparing kidney allograft survival and function in patients who received a subsequent pancreas-after-kidney transplant vs those who did not, graft survival was superior after 5 years, and the estimated glomerular filtration rate was 10 mL/min higher in pancreas-after-kidney recipients.28 This improvement in renal function was not seen immediately after the pancreas transplant but became evident more than 4 years after establishment of normoglycemia. Somewhat similarly, reversal of diabetic changes in native kidney biopsies has been seen 10 years after pancreas transplant.29

Effect on neuropathy. In other studies, reversal of autonomic neuropathy and hypoglycemic unawareness and improvements in peripheral sensory-motor neuropathy have also been observed.30–32

Effect on retinopathy. Improvements in early-stage nonproliferative diabetic retinopathy and laser-treated proliferative lesions have been seen, even within short periods of follow-up.33 Other groups have shown a significantly higher proportion of improvement or stability of advanced diabetic retinopathy at 3 years after simultaneous pancreas-kidney transplant, compared with kidney transplant alone in patients with type 1 diabetes.34

Effect on heart disease. Salutary effects on cardiovascular risk factors and amelioration of cardiac morphology and functional cardiac indices have been seen within the first posttransplant year.35 Moreover, with longer follow-up (nearly 4 years), simultaneous pancreas-kidney recipients with functioning pancreas grafts were found to have less progression of coronary atherosclerosis than simultaneous pancreas-kidney recipients with early pancreas graft loss.36 These data provide a potential pathophysiologic mechanism for the long-term survival advantage seen in uremic type 1 diabetic patients undergoing simultaneous pancreas-kidney transplant.

In the aggregate, these findings suggest that, in the absence of surgical and immunosuppression-related complications, a functioning pancreas allograft can alter the progress of diabetic complications. As an extension of these results, pancreas transplant done earlier in the course of diabetes may have an even greater impact.

References
  1. Centers for Disease Control and Prevention (CDC). National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed August 12, 2015.
  2. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in US diabetes care, 1999–2010. N Engl J Med 2013; 368:1613–1624.
  3. Jeon JY, Kim DJ, Ko SH, et al; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Current status of glycemic control of patients with diabetes in Korea: the fifth Korea national health and nutrition examination survey. Diabetes Metab J 2014; 38:197–203.
  4. Govan L, Wu O, Briggs A, et al; Scottish Diabetes Research Network Epidemiology Group. Achieved levels of HbA1c and likelihood of hospital admission in people with type 1 diabetes in the Scottish population: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetes Care 2011; 34:1992–1997.
  5. Bryant W, Greenfield JR, Chisholm DJ, Campbell LV. Diabetes guidelines: easier to preach than to practise? Med J Aust 2006; 185:305–309.
  6. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967; 61:827–837.
  7. Gruessner AC, Gruessner RW. Pancreas transplant outcomes for United States and non United States cases as reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011. Clin Transpl 2012: 23–40.
  8. Israni AK, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2012 Annual Data Report: pancreas. Am J Transplant 2014; 14(suppl 1):45–68
  9. Gruessner RW, Gruessner AC. Pancreas transplant alone: a procedure coming of age. Diabetes Care 2013; 36:2440–2447.
  10. Axelrod DA, Sung RS, Meyer KH, Wolfe RA, Kaufman DB. Systematic evaluation of pancreas allograft quality, outcomes and geographic variation in utilization. Am J Transplant 2010; 10:837–845.
  11. Wiseman AC, Wainright JL, Sleeman E, et al. An analysis of the lack of donor pancreas utilization from younger adult organ donors. Transplantation 2010; 90:475–480.
  12. Gruessner RW, Gruessner AC. The current state of pancreas transplantation. Nat Rev Endocrinol 2013; 9:555–562.
  13. Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant 2012; 26:550–557.
  14. Sollinger HW, Odorico JS, Becker YT, D’Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg 2009; 250:618–630.
  15. Humar A, Kandaswamy R, Granger D, Gruessner RW, Gruessner AC, Sutherland DE. Decreased surgical risks of pancreas transplantation in the modern era. Ann Surg 2000; 231:269–275.
  16. Sampaio MS, Reddy PN, Kuo HT, et al. Obesity was associated with inferior outcomes in simultaneous pancreas kidney transplant. Transplantation 2010; 89:1117–1125.
  17. Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant 2013; 13:1840–1849.
  18. Fridell JA, Mangus RS, Taber TE, et al. Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation. Clin Transplant 2011; 25:E366–E374.
  19. Tai DS, Hong J, Busuttil RW, Lipshutz GS. Low rates of short- and long-term graft loss after kidney-pancreas transplant from a single center. JAMA Surg 2013; 148:368–373.
  20. Bazerbachi F, Selzner M, Marquez MA, et al. Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results. Transplantation 2013; 95:489–494.
  21. Laftavi MR, Pankewycz O, Gruessner A, et al. Long-term outcomes of pancreas after kidney transplantation in small centers: is it justified? Transplant Proc 2014; 46:1920–1923.
  22. Stratta RJ, Farney AC, Orlando G, Farooq U, Al-Shraideh Y, Rogers J. Similar results with solitary pancreas transplantation compared with simultaneous pancreas-kidney transplantation in the new millennium. Transplant Proc 2014; 46:1924–1927.
  23. Siskind E, Maloney C, Akerman M, et al. An analysis of pancreas transplantation outcomes based on age groupings—an update of the UNOS database. Clin Transplant 2014; 28:990–994.
  24. Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 2001; 71:82–90.
  25. Reddy KS, Stablein D, Taranto S, et al. Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure. Am J Kidney Dis 2003; 41:464–470.
  26. Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003; 290:2817–2823.
  27. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant 2004; 4:2018–2026.
  28. Kleinclauss F, Fauda M, Sutherland DE, et al. Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function. Clin Transplant 2009; 23:437–446.
  29. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339:69–75.
  30. Landgraf R. Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 1996; 39:1415–1424.
  31. Robertson RP. Update on transplanting beta cells for reversing type 1 diabetes. Endocrinol Metab Clin North Am 2010; 39:655–667.
  32. Robertson RP, Holohan TV, Genuth S. Therapeutic controversy: pancreas transplantation for type I diabetes. J Clin Endocrinol Metab 1998; 83:1868–1674.
  33. Giannarelli R, Coppelli A, Sartini MS, et al. Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients. Diabetologia 2006; 49:2977–2982.
  34. Koznarová R, Saudek F, Sosna T, et al. Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Cell Transplant 2000; 9:903–908.
  35. Coppelli A, Giannarelli R, Mariotti R, et al. Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients. Transplantation 2003; 76:974–976.
  36. Jukema JW, Smets YF, van der Pijl JW, et al. Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes. Diabetes Care 2002; 25:906–911.
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Kerr_PancreasTransplant.pdf
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Hannah R. Kerr, MD
New Mexico VA Healthcare System, Presbyterian Hospital, and University of New Mexico Hospital; Assistant Professor, University of New Mexico School of Medicine, Albuquerque

Betul Hatipoglu, MD
Department of Endocrinology, Diabetes and Metabolism and Brain Tumor and Neuro-Oncology Center, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venkatesh Krishnamurthi, MD
Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Cleveland Clinic

Address: Venkatesh Krishnamurthi, MD, Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Q10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: krishnv@ccf.org

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Type 2 Diabetes ICYMI
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Hannah R. Kerr, MD
Betul Hatipoglu, MD
Venkatesh Krishnamurthi, MD
Author(s)
Hannah R. Kerr, MD
Betul Hatipoglu, MD
Venkatesh Krishnamurthi, MD
Author and Disclosure Information

Hannah R. Kerr, MD
New Mexico VA Healthcare System, Presbyterian Hospital, and University of New Mexico Hospital; Assistant Professor, University of New Mexico School of Medicine, Albuquerque

Betul Hatipoglu, MD
Department of Endocrinology, Diabetes and Metabolism and Brain Tumor and Neuro-Oncology Center, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venkatesh Krishnamurthi, MD
Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Cleveland Clinic

Address: Venkatesh Krishnamurthi, MD, Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Q10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: krishnv@ccf.org

Author and Disclosure Information

Hannah R. Kerr, MD
New Mexico VA Healthcare System, Presbyterian Hospital, and University of New Mexico Hospital; Assistant Professor, University of New Mexico School of Medicine, Albuquerque

Betul Hatipoglu, MD
Department of Endocrinology, Diabetes and Metabolism and Brain Tumor and Neuro-Oncology Center, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venkatesh Krishnamurthi, MD
Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Cleveland Clinic

Address: Venkatesh Krishnamurthi, MD, Department of Urology; Director of Pancreas Transplantation, Glickman Urological and Kidney Institute, Q10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: krishnv@ccf.org

Article PDF
Kerr_PancreasTransplant.pdf
Article PDF
Kerr_PancreasTransplant.pdf

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.

 

 

SURGICAL COMPLICATIONS

Surgical complications have long been considered a limiting factor in the growth of pancreas transplant. Technical failure or loss of the graft within 90 days is most commonly due to graft thrombosis, leakage of the enteric anastomosis, or severe peripancreatic infection. The rate of technical failure has declined across all recipient categories and is currently about 9%.8

DO RECIPIENT FACTORS AFFECT OUTCOMES?

As mentioned above, the PDRI identifies donor factors that influence the 1-year graft survival rate. Recipient factors are also thought to play a role, although the influence of these factors has not been consistently demonstrated.

Humar et al15 found that recipient obesity (defined in this study as BMI > 25 kg/m2) and donor age over 40 were risk factors for early laparotomy after pancreas transplant.15 Moreover, patients undergoing early laparotomy had poorer graft survival outcomes.

This finding was reinforced by an analysis of 5,725 primary simultaneous pancreas-kidney recipients between 2000 and 2007. Obesity (BMI 30 ≥ kg/m2) was associated with increased rates of patient death, pancreas graft loss, and kidney graft loss at 3 years.16

More recently, Finger et al17 did not find a statistically significant association between recipient BMI and technical failure, but they did notice a trend toward increased graft loss with a BMI greater than 25 kg/m2. Similarly, others have not found a clear adverse association between recipient BMI and pancreas graft survival.

Intuitively, obesity and other recipient factors such as age, vascular disease, duration of diabetes, and dialysis should influence pancreas graft survival but have not been shown in analyses to carry an adverse effect.18 The inability to consistently find adverse effects of recipient characteristics is most likely due to the relative similarity between the vast majority of pancreas transplant recipients and the relatively small numbers of adverse events. In 98 consecutive pancreas transplants at our center between 2009 and 2014, the technical loss rate was 1.8% (unpublished data).

Acute rejection most commonly occurs during the first year and is usually reversible. More than 1 year after transplant, graft loss is due to chronic rejection, and death is usually from underlying cardiovascular disease.

The immunosuppressive regimens used in pancreas transplant are similar to those in kidney transplant. Since the pancreas is considered to be more immunogenic than other organs, most centers employ a strategy of induction immunosuppression with T-cell–depleting or interleukin 2-receptor antibodies. Maintenance immunosuppression consists of a calcineurin inhibitor (tacrolimus or cyclosporine), an antimetabolite (mycophenolate), and a corticosteroid.8

Immunosuppressive complications occur at a rate similar to that seen in other solid-organ transplants and include an increased risk of opportunistic infection and malignancy. The risk of these complications must be balanced against the patient’s risk of health decline with dialysis and insulin-based therapies.

OVERALL OUTCOMES ARE GOOD

The success rate of pancreas transplant is currently at its highest since the inception of the procedure. The unadjusted patient survival rate for all groups is over 96% at 1 year, and over 80% at 5 years.8 One-year patient survival after pancreas transplant alone, at better than 96%, is the highest of all organ transplant procedures.9

Patient survival 1 year after pancreas-alone transplant is > 96%

Several recently published single-center reviews of pancreas transplant since 2000 report patient survival rates of 96% to 100% at 1 year and 88% to 100% at 5 years.19–22 This variability is likely closely linked to donor and recipient selection, as centers performing smaller numbers of transplants tend to be more selective and, in turn, report higher patient survival rates.19,21

Long-term patient survival outcomes can be gathered from larger, registry-based reviews, accepting limitations in assessing causes of patient death. Siskind et al23 analyzed the outcomes of 20,854 US pancreas transplants done between 1996 and 2012 and found the 10-year patient survival rate ranged from 43% to 77% and was highly dependent on patient age at the time of the procedure.23 Patient survival after transplant must be balanced against the generally poor long-term survival prospects of diabetic patients on dialysis.

By type of transplant, pancreas graft survival rates at 1 year are 89% for simultaneous pancreas-kidney transplant, 86% for pancreas-after-kidney transplant, and 84% for pancreas-alone transplant. Graft survival rates at 5 years are 71% for simultaneous pancreas-kidney transplant, 65% for pancreas-after-kidney transplant, and 58% for pancreas-alone transplant.8,9

Simultaneous pancreas-kidney transplant has been shown to improve the survival rate compared with cadaveric kidney transplant alone in patients with type 1 diabetes and chronic kidney disease.24,25 The survival benefit of isolated pancreas transplant (after kidney transplant and alone) is not evident at 4-year follow-up compared with patients on the waiting list. However, the benefit for the individual patient must be considered by weighing the incapacities experienced with insulin-based treatments against the risks of surgery and immunosuppression.26,27 For patients who have experienced frequent and significant hypoglycemic episodes, particularly those requiring third-party assistance, pancreas transplant can be a lifesaving procedure.

Effects on secondary diabetic complications

Notwithstanding the effect on the patient’s life span, data from several studies of long-term pancreas transplant recipients suggest that secondary diabetic complications can be halted or even improved. Most of these studies examined the effect of restoring euglycemia in nephropathy and the subsequent influence on renal function.

Effect on renal function. Kleinclauss et al28 examined renal allograft function in type 1 diabetic recipients of living-donor kidney transplants. Comparing kidney allograft survival and function in patients who received a subsequent pancreas-after-kidney transplant vs those who did not, graft survival was superior after 5 years, and the estimated glomerular filtration rate was 10 mL/min higher in pancreas-after-kidney recipients.28 This improvement in renal function was not seen immediately after the pancreas transplant but became evident more than 4 years after establishment of normoglycemia. Somewhat similarly, reversal of diabetic changes in native kidney biopsies has been seen 10 years after pancreas transplant.29

Effect on neuropathy. In other studies, reversal of autonomic neuropathy and hypoglycemic unawareness and improvements in peripheral sensory-motor neuropathy have also been observed.30–32

Effect on retinopathy. Improvements in early-stage nonproliferative diabetic retinopathy and laser-treated proliferative lesions have been seen, even within short periods of follow-up.33 Other groups have shown a significantly higher proportion of improvement or stability of advanced diabetic retinopathy at 3 years after simultaneous pancreas-kidney transplant, compared with kidney transplant alone in patients with type 1 diabetes.34

Effect on heart disease. Salutary effects on cardiovascular risk factors and amelioration of cardiac morphology and functional cardiac indices have been seen within the first posttransplant year.35 Moreover, with longer follow-up (nearly 4 years), simultaneous pancreas-kidney recipients with functioning pancreas grafts were found to have less progression of coronary atherosclerosis than simultaneous pancreas-kidney recipients with early pancreas graft loss.36 These data provide a potential pathophysiologic mechanism for the long-term survival advantage seen in uremic type 1 diabetic patients undergoing simultaneous pancreas-kidney transplant.

In the aggregate, these findings suggest that, in the absence of surgical and immunosuppression-related complications, a functioning pancreas allograft can alter the progress of diabetic complications. As an extension of these results, pancreas transplant done earlier in the course of diabetes may have an even greater impact.

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.

 

 

SURGICAL COMPLICATIONS

Surgical complications have long been considered a limiting factor in the growth of pancreas transplant. Technical failure or loss of the graft within 90 days is most commonly due to graft thrombosis, leakage of the enteric anastomosis, or severe peripancreatic infection. The rate of technical failure has declined across all recipient categories and is currently about 9%.8

DO RECIPIENT FACTORS AFFECT OUTCOMES?

As mentioned above, the PDRI identifies donor factors that influence the 1-year graft survival rate. Recipient factors are also thought to play a role, although the influence of these factors has not been consistently demonstrated.

Humar et al15 found that recipient obesity (defined in this study as BMI > 25 kg/m2) and donor age over 40 were risk factors for early laparotomy after pancreas transplant.15 Moreover, patients undergoing early laparotomy had poorer graft survival outcomes.

This finding was reinforced by an analysis of 5,725 primary simultaneous pancreas-kidney recipients between 2000 and 2007. Obesity (BMI 30 ≥ kg/m2) was associated with increased rates of patient death, pancreas graft loss, and kidney graft loss at 3 years.16

More recently, Finger et al17 did not find a statistically significant association between recipient BMI and technical failure, but they did notice a trend toward increased graft loss with a BMI greater than 25 kg/m2. Similarly, others have not found a clear adverse association between recipient BMI and pancreas graft survival.

Intuitively, obesity and other recipient factors such as age, vascular disease, duration of diabetes, and dialysis should influence pancreas graft survival but have not been shown in analyses to carry an adverse effect.18 The inability to consistently find adverse effects of recipient characteristics is most likely due to the relative similarity between the vast majority of pancreas transplant recipients and the relatively small numbers of adverse events. In 98 consecutive pancreas transplants at our center between 2009 and 2014, the technical loss rate was 1.8% (unpublished data).

Acute rejection most commonly occurs during the first year and is usually reversible. More than 1 year after transplant, graft loss is due to chronic rejection, and death is usually from underlying cardiovascular disease.

The immunosuppressive regimens used in pancreas transplant are similar to those in kidney transplant. Since the pancreas is considered to be more immunogenic than other organs, most centers employ a strategy of induction immunosuppression with T-cell–depleting or interleukin 2-receptor antibodies. Maintenance immunosuppression consists of a calcineurin inhibitor (tacrolimus or cyclosporine), an antimetabolite (mycophenolate), and a corticosteroid.8

Immunosuppressive complications occur at a rate similar to that seen in other solid-organ transplants and include an increased risk of opportunistic infection and malignancy. The risk of these complications must be balanced against the patient’s risk of health decline with dialysis and insulin-based therapies.

OVERALL OUTCOMES ARE GOOD

The success rate of pancreas transplant is currently at its highest since the inception of the procedure. The unadjusted patient survival rate for all groups is over 96% at 1 year, and over 80% at 5 years.8 One-year patient survival after pancreas transplant alone, at better than 96%, is the highest of all organ transplant procedures.9

Patient survival 1 year after pancreas-alone transplant is > 96%

Several recently published single-center reviews of pancreas transplant since 2000 report patient survival rates of 96% to 100% at 1 year and 88% to 100% at 5 years.19–22 This variability is likely closely linked to donor and recipient selection, as centers performing smaller numbers of transplants tend to be more selective and, in turn, report higher patient survival rates.19,21

Long-term patient survival outcomes can be gathered from larger, registry-based reviews, accepting limitations in assessing causes of patient death. Siskind et al23 analyzed the outcomes of 20,854 US pancreas transplants done between 1996 and 2012 and found the 10-year patient survival rate ranged from 43% to 77% and was highly dependent on patient age at the time of the procedure.23 Patient survival after transplant must be balanced against the generally poor long-term survival prospects of diabetic patients on dialysis.

By type of transplant, pancreas graft survival rates at 1 year are 89% for simultaneous pancreas-kidney transplant, 86% for pancreas-after-kidney transplant, and 84% for pancreas-alone transplant. Graft survival rates at 5 years are 71% for simultaneous pancreas-kidney transplant, 65% for pancreas-after-kidney transplant, and 58% for pancreas-alone transplant.8,9

Simultaneous pancreas-kidney transplant has been shown to improve the survival rate compared with cadaveric kidney transplant alone in patients with type 1 diabetes and chronic kidney disease.24,25 The survival benefit of isolated pancreas transplant (after kidney transplant and alone) is not evident at 4-year follow-up compared with patients on the waiting list. However, the benefit for the individual patient must be considered by weighing the incapacities experienced with insulin-based treatments against the risks of surgery and immunosuppression.26,27 For patients who have experienced frequent and significant hypoglycemic episodes, particularly those requiring third-party assistance, pancreas transplant can be a lifesaving procedure.

Effects on secondary diabetic complications

Notwithstanding the effect on the patient’s life span, data from several studies of long-term pancreas transplant recipients suggest that secondary diabetic complications can be halted or even improved. Most of these studies examined the effect of restoring euglycemia in nephropathy and the subsequent influence on renal function.

Effect on renal function. Kleinclauss et al28 examined renal allograft function in type 1 diabetic recipients of living-donor kidney transplants. Comparing kidney allograft survival and function in patients who received a subsequent pancreas-after-kidney transplant vs those who did not, graft survival was superior after 5 years, and the estimated glomerular filtration rate was 10 mL/min higher in pancreas-after-kidney recipients.28 This improvement in renal function was not seen immediately after the pancreas transplant but became evident more than 4 years after establishment of normoglycemia. Somewhat similarly, reversal of diabetic changes in native kidney biopsies has been seen 10 years after pancreas transplant.29

Effect on neuropathy. In other studies, reversal of autonomic neuropathy and hypoglycemic unawareness and improvements in peripheral sensory-motor neuropathy have also been observed.30–32

Effect on retinopathy. Improvements in early-stage nonproliferative diabetic retinopathy and laser-treated proliferative lesions have been seen, even within short periods of follow-up.33 Other groups have shown a significantly higher proportion of improvement or stability of advanced diabetic retinopathy at 3 years after simultaneous pancreas-kidney transplant, compared with kidney transplant alone in patients with type 1 diabetes.34

Effect on heart disease. Salutary effects on cardiovascular risk factors and amelioration of cardiac morphology and functional cardiac indices have been seen within the first posttransplant year.35 Moreover, with longer follow-up (nearly 4 years), simultaneous pancreas-kidney recipients with functioning pancreas grafts were found to have less progression of coronary atherosclerosis than simultaneous pancreas-kidney recipients with early pancreas graft loss.36 These data provide a potential pathophysiologic mechanism for the long-term survival advantage seen in uremic type 1 diabetic patients undergoing simultaneous pancreas-kidney transplant.

In the aggregate, these findings suggest that, in the absence of surgical and immunosuppression-related complications, a functioning pancreas allograft can alter the progress of diabetic complications. As an extension of these results, pancreas transplant done earlier in the course of diabetes may have an even greater impact.

References
  1. Centers for Disease Control and Prevention (CDC). National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed August 12, 2015.
  2. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in US diabetes care, 1999–2010. N Engl J Med 2013; 368:1613–1624.
  3. Jeon JY, Kim DJ, Ko SH, et al; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Current status of glycemic control of patients with diabetes in Korea: the fifth Korea national health and nutrition examination survey. Diabetes Metab J 2014; 38:197–203.
  4. Govan L, Wu O, Briggs A, et al; Scottish Diabetes Research Network Epidemiology Group. Achieved levels of HbA1c and likelihood of hospital admission in people with type 1 diabetes in the Scottish population: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetes Care 2011; 34:1992–1997.
  5. Bryant W, Greenfield JR, Chisholm DJ, Campbell LV. Diabetes guidelines: easier to preach than to practise? Med J Aust 2006; 185:305–309.
  6. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967; 61:827–837.
  7. Gruessner AC, Gruessner RW. Pancreas transplant outcomes for United States and non United States cases as reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011. Clin Transpl 2012: 23–40.
  8. Israni AK, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2012 Annual Data Report: pancreas. Am J Transplant 2014; 14(suppl 1):45–68
  9. Gruessner RW, Gruessner AC. Pancreas transplant alone: a procedure coming of age. Diabetes Care 2013; 36:2440–2447.
  10. Axelrod DA, Sung RS, Meyer KH, Wolfe RA, Kaufman DB. Systematic evaluation of pancreas allograft quality, outcomes and geographic variation in utilization. Am J Transplant 2010; 10:837–845.
  11. Wiseman AC, Wainright JL, Sleeman E, et al. An analysis of the lack of donor pancreas utilization from younger adult organ donors. Transplantation 2010; 90:475–480.
  12. Gruessner RW, Gruessner AC. The current state of pancreas transplantation. Nat Rev Endocrinol 2013; 9:555–562.
  13. Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant 2012; 26:550–557.
  14. Sollinger HW, Odorico JS, Becker YT, D’Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg 2009; 250:618–630.
  15. Humar A, Kandaswamy R, Granger D, Gruessner RW, Gruessner AC, Sutherland DE. Decreased surgical risks of pancreas transplantation in the modern era. Ann Surg 2000; 231:269–275.
  16. Sampaio MS, Reddy PN, Kuo HT, et al. Obesity was associated with inferior outcomes in simultaneous pancreas kidney transplant. Transplantation 2010; 89:1117–1125.
  17. Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant 2013; 13:1840–1849.
  18. Fridell JA, Mangus RS, Taber TE, et al. Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation. Clin Transplant 2011; 25:E366–E374.
  19. Tai DS, Hong J, Busuttil RW, Lipshutz GS. Low rates of short- and long-term graft loss after kidney-pancreas transplant from a single center. JAMA Surg 2013; 148:368–373.
  20. Bazerbachi F, Selzner M, Marquez MA, et al. Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results. Transplantation 2013; 95:489–494.
  21. Laftavi MR, Pankewycz O, Gruessner A, et al. Long-term outcomes of pancreas after kidney transplantation in small centers: is it justified? Transplant Proc 2014; 46:1920–1923.
  22. Stratta RJ, Farney AC, Orlando G, Farooq U, Al-Shraideh Y, Rogers J. Similar results with solitary pancreas transplantation compared with simultaneous pancreas-kidney transplantation in the new millennium. Transplant Proc 2014; 46:1924–1927.
  23. Siskind E, Maloney C, Akerman M, et al. An analysis of pancreas transplantation outcomes based on age groupings—an update of the UNOS database. Clin Transplant 2014; 28:990–994.
  24. Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 2001; 71:82–90.
  25. Reddy KS, Stablein D, Taranto S, et al. Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure. Am J Kidney Dis 2003; 41:464–470.
  26. Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003; 290:2817–2823.
  27. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant 2004; 4:2018–2026.
  28. Kleinclauss F, Fauda M, Sutherland DE, et al. Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function. Clin Transplant 2009; 23:437–446.
  29. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339:69–75.
  30. Landgraf R. Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 1996; 39:1415–1424.
  31. Robertson RP. Update on transplanting beta cells for reversing type 1 diabetes. Endocrinol Metab Clin North Am 2010; 39:655–667.
  32. Robertson RP, Holohan TV, Genuth S. Therapeutic controversy: pancreas transplantation for type I diabetes. J Clin Endocrinol Metab 1998; 83:1868–1674.
  33. Giannarelli R, Coppelli A, Sartini MS, et al. Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients. Diabetologia 2006; 49:2977–2982.
  34. Koznarová R, Saudek F, Sosna T, et al. Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Cell Transplant 2000; 9:903–908.
  35. Coppelli A, Giannarelli R, Mariotti R, et al. Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients. Transplantation 2003; 76:974–976.
  36. Jukema JW, Smets YF, van der Pijl JW, et al. Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes. Diabetes Care 2002; 25:906–911.
References
  1. Centers for Disease Control and Prevention (CDC). National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed August 12, 2015.
  2. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in US diabetes care, 1999–2010. N Engl J Med 2013; 368:1613–1624.
  3. Jeon JY, Kim DJ, Ko SH, et al; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Current status of glycemic control of patients with diabetes in Korea: the fifth Korea national health and nutrition examination survey. Diabetes Metab J 2014; 38:197–203.
  4. Govan L, Wu O, Briggs A, et al; Scottish Diabetes Research Network Epidemiology Group. Achieved levels of HbA1c and likelihood of hospital admission in people with type 1 diabetes in the Scottish population: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetes Care 2011; 34:1992–1997.
  5. Bryant W, Greenfield JR, Chisholm DJ, Campbell LV. Diabetes guidelines: easier to preach than to practise? Med J Aust 2006; 185:305–309.
  6. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967; 61:827–837.
  7. Gruessner AC, Gruessner RW. Pancreas transplant outcomes for United States and non United States cases as reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011. Clin Transpl 2012: 23–40.
  8. Israni AK, Skeans MA, Gustafson SK, et al. OPTN/SRTR 2012 Annual Data Report: pancreas. Am J Transplant 2014; 14(suppl 1):45–68
  9. Gruessner RW, Gruessner AC. Pancreas transplant alone: a procedure coming of age. Diabetes Care 2013; 36:2440–2447.
  10. Axelrod DA, Sung RS, Meyer KH, Wolfe RA, Kaufman DB. Systematic evaluation of pancreas allograft quality, outcomes and geographic variation in utilization. Am J Transplant 2010; 10:837–845.
  11. Wiseman AC, Wainright JL, Sleeman E, et al. An analysis of the lack of donor pancreas utilization from younger adult organ donors. Transplantation 2010; 90:475–480.
  12. Gruessner RW, Gruessner AC. The current state of pancreas transplantation. Nat Rev Endocrinol 2013; 9:555–562.
  13. Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant 2012; 26:550–557.
  14. Sollinger HW, Odorico JS, Becker YT, D’Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg 2009; 250:618–630.
  15. Humar A, Kandaswamy R, Granger D, Gruessner RW, Gruessner AC, Sutherland DE. Decreased surgical risks of pancreas transplantation in the modern era. Ann Surg 2000; 231:269–275.
  16. Sampaio MS, Reddy PN, Kuo HT, et al. Obesity was associated with inferior outcomes in simultaneous pancreas kidney transplant. Transplantation 2010; 89:1117–1125.
  17. Finger EB, Radosevich DM, Dunn TB, et al. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant 2013; 13:1840–1849.
  18. Fridell JA, Mangus RS, Taber TE, et al. Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation. Clin Transplant 2011; 25:E366–E374.
  19. Tai DS, Hong J, Busuttil RW, Lipshutz GS. Low rates of short- and long-term graft loss after kidney-pancreas transplant from a single center. JAMA Surg 2013; 148:368–373.
  20. Bazerbachi F, Selzner M, Marquez MA, et al. Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results. Transplantation 2013; 95:489–494.
  21. Laftavi MR, Pankewycz O, Gruessner A, et al. Long-term outcomes of pancreas after kidney transplantation in small centers: is it justified? Transplant Proc 2014; 46:1920–1923.
  22. Stratta RJ, Farney AC, Orlando G, Farooq U, Al-Shraideh Y, Rogers J. Similar results with solitary pancreas transplantation compared with simultaneous pancreas-kidney transplantation in the new millennium. Transplant Proc 2014; 46:1924–1927.
  23. Siskind E, Maloney C, Akerman M, et al. An analysis of pancreas transplantation outcomes based on age groupings—an update of the UNOS database. Clin Transplant 2014; 28:990–994.
  24. Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 2001; 71:82–90.
  25. Reddy KS, Stablein D, Taranto S, et al. Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure. Am J Kidney Dis 2003; 41:464–470.
  26. Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003; 290:2817–2823.
  27. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant 2004; 4:2018–2026.
  28. Kleinclauss F, Fauda M, Sutherland DE, et al. Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function. Clin Transplant 2009; 23:437–446.
  29. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339:69–75.
  30. Landgraf R. Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 1996; 39:1415–1424.
  31. Robertson RP. Update on transplanting beta cells for reversing type 1 diabetes. Endocrinol Metab Clin North Am 2010; 39:655–667.
  32. Robertson RP, Holohan TV, Genuth S. Therapeutic controversy: pancreas transplantation for type I diabetes. J Clin Endocrinol Metab 1998; 83:1868–1674.
  33. Giannarelli R, Coppelli A, Sartini MS, et al. Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients. Diabetologia 2006; 49:2977–2982.
  34. Koznarová R, Saudek F, Sosna T, et al. Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Cell Transplant 2000; 9:903–908.
  35. Coppelli A, Giannarelli R, Mariotti R, et al. Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients. Transplantation 2003; 76:974–976.
  36. Jukema JW, Smets YF, van der Pijl JW, et al. Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes. Diabetes Care 2002; 25:906–911.
Issue
Cleveland Clinic Journal of Medicine - 82(11)
Issue
Cleveland Clinic Journal of Medicine - 82(11)
Page Number
738-744
Page Number
738-744
Publications
Cleveland Clinic Journal of Medicine
Type 2 Diabetes ICYMI
Publications
Cleveland Clinic Journal of Medicine
Type 2 Diabetes ICYMI
Topics
Diabetes
Nephrology
Endocrinology
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Pancreas transplant for diabetes mellitus
Display Headline
Pancreas transplant for diabetes mellitus
Legacy Keywords
Pancreas, pancreas transplant, pancreas transplantation, diabetes, Hannah Kerr, Betul Hatipoglu, Venkatesh Krishnamurthi
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Pancreas, pancreas transplant, pancreas transplantation, diabetes, Hannah Kerr, Betul Hatipoglu, Venkatesh Krishnamurthi
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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.
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