Long-term Success With Pancreas Transplant Alone in Diabetes

Miriam E. Tucker

June 19, 2014

SAN FRANCISCO – The University of Pisa's experience with pancreas transplant alone suggests that long-term success is possible for the treatment of selected patients with type 1 diabetes.

Few long-term data have been available for pancreas transplant alone, Margherita Occhipinti, MD, an endocrinologist at the University of Pisa, told the American Diabetes Association (ADA) 2014 Scientific Sessions. There is greater experience with simultaneous pancreas/kidney transplants, performed with the rationale that if the patient has renal failure due to the diabetes and needs a kidney transplant, little further risk is incurred by also transplanting a pancreas if one is available, she explained.

Her center began performing simultaneous pancreas/kidney transplants in 1996, followed by its first pancreas transplant alone in 2000. She reported the results of 10-year follow-up in 34 patients who received pancreas transplant alone between 2000 and 2003.

Session moderator James A. M. Shaw, PhD, professor of regenerative medicine for diabetes at Newcastle University, United Kingdom, told Medscape Medical News that the risk/benefit equation for pancreas transplant alone has typically been more difficult to assess.

"The solid pancreas transplant is a fantastic treatment if you also have a kidney transplant....But, it's only for the small number of people whose lives are threatened by being on dialysis. The pancreas transplant by itself has been a lot harder."

The concern relates to weighing the risks for immunosuppression, particularly the renal ones, against the benefit of eliminating the diabetes, he said. So "if those kidneys get worse than they would have with the diabetes, is it really the right procedure to do?

Experiences like that of the Pisa group show that "the data are getting very strong that [pancreas transplant alone] does help prevent other complications, but it doesn't do it overnight," he said. "You need to get beyond that first-year risk to have any chance of living longer than not having it. But once you get out beyond one year, if it's going well, your life is transformed."

One Center's Experience: 65% of People Insulin Independent after 10 years

Dr. Occhipinti presented her institution's 10-year follow-up data for the 17 male and 17 female pancreas-transplant-alone recipients. Mean age at transplant was 37 years, mean body mass index 23.5 kg/m2, and mean duration of type 1 diabetes was 24 years. All underwent pancreas transplant alone with the portal-enteric drainage approach. Immunosuppression consisted of basiliximab and high-dose steroids as induction, followed by mycophenolate mofetil [CellCept, Roche], tacrolimus, and low-dose steroid as maintenance treatment.

Patient survival at 10 years was 97%, with the 1 death being due to stroke at 5 years posttransplant in a patient with a functioning graft. Pancreatic graft survival was 65%, with the 12 failures due to technical reasons in 1, acute rejection in 2, and chronic rejection in the other 9.

All of the patients with functioning grafts at 10 years were insulin independent, with mean fasting plasma glucose (FPG) levels of 96 mg/dL post–pancreas transplant compared with 230 mg/dL before the procedure. Average HbA1c values were 5.8% at 10 years, compared with 8.3% prior to the transplant (P < .001 for both FPG and HbA1c). Endogenous C-peptide secretion was 2.8 ng/mL at 10 years, vs 0.08 ng/mL before the transplant ( P < .001).

Total cholesterol also improved 10 years after pancreas transplant alone, at 157 mg/dL compared with 193 mg/dL beforehand (P < 0.001), as did LDL cholesterol, at 95 mg/dL vs 128 mg/dL (P < 0.001). No major changes were seen in HDL cholesterol or triglycerides.

Blood pressure improved slightly within the first 5 years but was not significantly changed from baseline at 10 years, Dr. Occhipinti reported.

Several indexes of cardiac diastolic function also improved significantly, including an increase in left ventricular ejection fraction (LVEF) from 54.1% to 58.9% (P < .01) after transplantation. The reason for the LVEF improvement isn't clear, but it may be that glycemic control could lead to reduced load on the heart, she said in response to a question from the audience.

The patients had an average yearly decline of 1.8 mL/min in estimated glomerular filtration rate (eGFR) calculated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) study equation. One patient required a kidney transplant after the pancreas transplant alone.

No patient had serious infection complications. There were 3 cancers, one of blood and 2 of the lung.

"Pancreas transplant alone can be considered an effective and safe procedure for selected type 1 diabetic patients. An integrated approach is recommended for appropriate evaluation and careful monitoring of patients," Dr Occhipinti concluded.

"When It Works, It Works Fantastically"

Dr. Shaw told Medscape Medical News, "Pancreas transplant alone, when it works, it works fantastically. As soon as they take the clamp off, the person is off insulin. And they'll stay off insulin as long as they don't lose the graft. The problem is, you're going to lose at least 20% of those grafts....It's a fantastic procedure, but you can't promise someone it's going to work in 100% or even three-quarters of cases for 3 years."

He said that other single centers have achieved similar success to that of the Pisa group. And while there has been a shift away from pancreas transplant alone toward islet cells in some places — for example, in the United Kingdom — he believes patients should be offered the choice.

"I think this is for the patients to decide. They have to ask themselves if they can accept a 2% to 5% risk of dying in a year from the procedure to get rid of the diabetes. If you get to a year and it's working, you're likely to be off insulin, and life [will be] completely normal for 10 years," whereas with islets, there is always the chance that insulin may be needed again.

In an ideal world, he said, patients with type 1 diabetes would have access to all options, including the best pump and sensor technology, education, team care, and all the transplant options. "There mustn't be these evangelical silos, where if you live in one place you get a pancreas and another you get islets. We can turn things around for virtually everyone with type 1. I think it's really exciting. It's a positive time."

Dr. Occhipinti and Dr. Shaw have reported no relevant financial relationships.

American Diabetes Association 2014 Scientific Sessions; June 14, 2014. Abstract 82-OR.


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