Experts discussed the evolving landscape of pancreas transplantation for people with type 1 and type 2 diabetes on Sunday, June 5, during the session Pancreas Transplantation in the 21st Century—Current Outcomes and Novel Indications. The session was livestreamed and can be viewed on-demand by registered meeting participants at ADA2022.org. If you haven’t registered for the 82nd Scientific Sessions, register today to access the valuable meeting content.
Raja Kandaswamy, MD, the Sutherland-Butterfield Professor of Surgery at the University of Minnesota Medical School, reviewed indications and current outcomes of pancreas transplant alone (PTA) and simultaneous pancreas-kidney (SPK) transplant for diabetes.
“SPK transplants are associated with excellent long-term results and should be offered to all uremic insulin-dependent diabetics who qualify for a kidney transplant, preferably done simultaneously, but they could be done sequentially,” Dr. Kandaswamy said. “Solitary pancreas transplants should be selectively offered to diabetics with severe hypoglycemic episodes or progressive secondary complications in spite of optimal medical management.”
Looking to the future, Dr. Kandaswamy said pancreas transplants will need to adapt to available and evolving therapies, such as closed-loop insulin pumps, metabolic surgical options, islet transplantation, stem cell transplantation, and potentially even xenotransplantation.
“The pancreas transplant will have to find a place within this landscape,” he said. “SPK transplants, though, will continue to be a strong option based on excellent short- and long-term results, but long-term results of solitary pancreas transplants need to improve—they must improve to stay relevant.”
Carrie Thiessen, MD, PhD, Assistant Professor of Surgery at the University of Wisconsin-Madison, discussed the impact of pancreas transplantation on secondary complications of diabetes, the incidence of which increases with the duration of diabetes. Many complications manifest only after 10 or more years of hyperglycemia, she noted.
“Most patients are not evaluated for transplant until they’ve had diabetes for 15 or more years, therefore the incidence of secondary complications at the time of the evaluation is very high,” Dr. Thiessen said.
A third of patients or more have severe nephropathy, more than half of patients over the age of 35 have moderate or severe cardiovascular disease, up to 90% of patients report some symptoms of neuropathy, and the vast majority have some degree of retinopathy at the time of evaluation, she said.
While more long-term data is needed, she said a growing number of studies suggest that pancreas transplantation may beneficially impact many of the secondary complications of diabetes.
“Pancreas transplant likely prevents further progression of diabetic nephropathy and may even reverse it over a period of five to 10 years of normal glycemia,” Dr. Thiessen said. “Additionally, pancreas transplant likely decreases the risk of cardiovascular death and likely prevents some of the progression of cardiovascular disease. The evidence for the impact of pancreas transplant on peripheral neuropathy is mixed, but there is evidence that pancreas transplant stabilizes diabetic retinopathy in many patients.”
Umesh Masharani, MD, Professor of Medicine in the Division of Endocrinology at the University of California, San Francisco, discussed the management of type 2 diabetes after pancreas transplantation.
“Changes in the inclusion criteria for pancreas transplant in 2019 increased access for people with type 2 diabetes. Prior to 2019, SPK was really only for individuals on insulin with very low levels of C-peptide or, if you had C-peptide, your BMI had to be less than 30,” Dr. Masharani said. “While the removal of the BMI and the C-peptide from the selection criteria has increased access for type 2 patients to get SPK, they still have to be on insulin to qualify for transplant.”
For patients who develop post-transplant diabetes within six months of the original transplant, the recommended treatment is insulin plus or minus a secretagogue, he said. Patients who develop diabetes later, when they are on long-term immunosuppression management, can be started on metformin and possibly a secretagogue afterwards, he said.
“The DPP4-inhibitors have been used, but there is a lack of good clinical trial, and we’ve started using the GLP-1 (glucagon-like peptide-1) receptor agonists in our kidney transplant patients and it seems to be fairly safe, so I think you could use them,” Dr. Masharani said. “And I think the SGLT-2 (sodium-glucose cotransporter 2) inhibitors, especially if patients don’t have high risk of urinary tract infection or urosepsis, might potentially be a really good group of drugs to use in this population and may have an effect on long-term outcomes.”