The odds of undergoing a successful pancreas transplantation for people with diabetes have increased in recent years, but the number of adults undergoing the procedure is declining, according to a review article.

A study published in American Journal of Transplantation in 2016 detailed a steady increase in the survival rate of people who undergo a simultaneous pancreas and kidney transplant and those who have a pancreas transplant after a kidney transplant. The proportion of those who had a functioning pancreas after any type of transplantation also increased from 1999-2003 to 2009-2013.

Pancreas transplantation success rates have increased in the past 20 years, but the number of adults undergoing the procedure in the U.S. has declined. A report published in Current Opinion in Organ Transplantation in 2016 found the number of pancreas transplantations taking place in the U.S. peaked in 2003 before steadily declining from 2004 to 2013.

The decline in surgery rates has continued in recent years. In a review published in The Journal of Clinical Endocrinology & Metabolism, Jonathan A. Fridell, MD, FACS, professor of surgery, chief of abdominal transplant surgery and director of pancreas transplantation at Indiana University School of Medicine, and colleagues wrote that from 2005 to 2021 in the U.S., the number of simultaneous kidney and pancreas transplantations declined 9%, pancreas transplantations after kidney transplantation declined 85%, and pancreas transplantations alone decreased by 63%. Similar declines have been observed in other countries as well.

“Kidney and pancreas transplantation have been a recognized standard of care for certain patient populations for more than 20 years, pancreas transplant alone for slightly less than that,” Fridell told Healio. “There isn’t a therapy that competes with them for the patients that have the right indications. Yet when we look at guidelines for management of patients with diabetic nephropathy and guidelines for patients with diabetes, most often these treatment pathways aren’t explored. I think it’s because there’s hope that there’ll be something better that comes along, there’s a belief that insulin therapy must be able to work and there is a concern that this is a potentially morbid operation.”

Healio spoke with Fridell about the benefits and risks of pancreatic transplantation for people with diabetes, factors behind the decline in transplantation in recent years, and reasons health care professionals should better educate people with type 1 or type 2 diabetes who may be candidates for the procedure.

Healio:Can you provide some background on pancreas transplantation as it pertains to people with diabetes? What are some of the benefits and risks of this procedure?

Fridell: Pancreas transplantation is not new. The first pancreas transplant was performed in the late 1960s at the University of Minnesota. In the operation, you add an extra pancreas, you don’t take out the original pancreas, you give them a second one. The point is if somebody is not making enough insulin to regulate their glucose, if you give them an extra pancreas, that one should make the insulin that they need. It’s very much like the way that we add a kidney when somebody is not making enough or good enough urine; that way we can get them out of renal failure and off of dialysis.

The risks are that it’s a major abdominal surgery. Any time you do an organ transplant, there’s a risk that the blood supply will clot off. For pancreas transplants, it’s probably slightly more common than for other types of transplants. Also, the pancreas is attached to the intestine, very rarely to the bladder, so there’s a risk that the attachments might leak. But all of these are uncommon complications.

Complications are typically graft-threatening, meaning that you can lose the pancreas because of them. They can be, but are not usually, life-threatening. And then there are the risks of lifelong immunosuppression. So, instead of the risk for diabetes where the patients might get vision loss or limb loss or loss of their kidney function, they trade that off for immunosuppression, which has toxicity, and puts patients at risk for opportunistic infections and cancers.

Most of the time we do pancreas transplants along with another organ, with the logic being that since they’re committed to lifelong immunosuppression for the other organ, they might as well not be diabetic. The vast majority of those are kidney transplants for diabetic nephropathy or diabetic kidney disease. The very select group of patients that qualify for a transplant are those patients who need a kidney, or for patients with life-threatening complications of diabetes, with the most common one of those being hypoglycemia unawareness. In that group of patients, we would also include patients who’ve had their pancreas removed for noncancerous reasons, like chronic pancreatitis.

Healio:Could pancreas transplantation be performed in a wider population of people with diabetes?

Fridell: Originally, this operation was reserved for patients with specifically type 1 diabetes, due to the risk for technical complications. We used to also restrict it to fairly straightforward candidates — so younger recipients with not a lot of vascular disease and not very overweight.

Recently, we’ve expanded the number of people who are suitable for this operation. We’re offering it to older patients, which is good because our recipient population is aging. Most programs offer into age 50 to 59 years, many programs into age 60 to 69 years, and very few, but some programs up into age 70 years and older. Patients with higher BMI are also being offered transplants.

What’s really interesting is nowadays we’re also offering it to patients with type 2 diabetes. That’s actually becoming a very common reason, to get a kidney and a pancreas transplant together for type 2 diabetes.

Healio:Is there a reason diabetes care professionals are hesitant to recommend a pancreas transplant for patients?

Fridell: There’s a long memory for the early history of pancreas transplantation from when this operation was first introduced. At that time, there were issues and complications during the period when we were figuring out how to do the operation and fine-tuning the surgical techniques, preservation solutions, postoperative management and immunosuppression, as was the case for every other type of transplant that we’ve done. There’s a period of learning and figuring steps out, and there’s a long memory for what pancreas transplants looked like during these early years and probably up until the late 1990s. But we’ve changed the technical aspects of the operation. We have better preservation solutions, immunosuppression has evolved, and we’ve become more experienced. We’re better at understanding complications and, therefore, predicting and preventing complications. Graft survival has improved significantly, and the technical graft loss has gone way down.

Healio:Why has there been a decline in the number of pancreas transplantation procedures over the past 20 years?

Fridell: There are many reasons, but probably the most prominent of those is we’re very tightly regulated, and the expectation is that we’re going to have excellent outcomes with every transplant that we do. As a field, we’ve become a little bit more cautious and a little bit more risk-averse, which has resulted in improved outcomes, but fewer numbers of organs getting used.

There have been some misconceptions about which combinations of organs to do. There certainly are some issues with referrals. For the kidney and pancreas patients, we usually capture those at transplant centers that do pancreas transplants when they come in for their kidney, but there are many programs that don’t offer pancreas transplants, or only offer them with very restricted criteria, so those patients might not get captured. Also, the patients who would benefit from getting just a pancreas because of their life-threatening complications, they remain in the diabetologists’ care with optimized medical therapy, which isn’t as good as a pancreas transplant.

Healio:What changes need to be made to increase uptake of pancreas transplantation for people with diabetes?

Fridell: As a medical community, we have to identify the patients that would be suitable candidates for this, think about it at the proper time and refer the patients. We have to educate the patients with diabetes because patients are allowed to refer themselves to transplant hospitals and if they are aware that this is an option — almost all pancreas transplant centers would welcome them. If they aren’t candidates, they can at least have the conversation about what’s involved. Perhaps some of the patients that we see might not be a candidate for pancreas transplant, but once it becomes approved, might be candidates for an islet transplant.

At transplant hospitals, there should be a pathway that when a patient gets referred for a kidney transplant, if they are a good candidate for a pancreas transplant, then there should be a mechanism for either consultation or referral to a sender that does pancreas transplants, so that the patients are informed and could decide which procedure they would like.

References:

• Fridell JA, et al. J Clin Endocrinol Metab. 2022;doi:10.1210/clinem/dgac644.
• Stratta RJ, et al. Am J Transplant. 2016;doi:10.1111/ajt.13890.
• Stratta RJ, et al. Curr Opin Organ Transplant. 2016;doi:10.1097/MOT.0000000000000319.