Is Transplant an Option? Alternative Therapies for Patients with Type 1 Diabetes
A little over 300 million people worldwide have type 1 diabetes. In the U.S., cases overall skew more heavily toward type 2. So of the 30 million total Americans with diabetes, the percentage with type 1 is just around 5%, or 1.5 million people.
That’s a significant number of people whose day-to-day lives are interrupted by finger pricks and insulin injections, not to mention the threat of serious, sometimes fatal complications. Fortunately, we’ve come a long way in our understanding of this challenging autoimmune disorder and have made great strides in our ability to manage it effectively.
The UVA Center for Diabetes Technology is playing an integral role in advancing type 1 diabetes treatment, developing innovative automated devices that can alleviate some of the burdens of monitoring blood glucose levels and administering insulin. One of these devices, the artificial pancreas system, called Control-IQ, was approved by the U.S. Food and Drug Administration in early 2020.
“UVA mathematician Boris Kovatchev [PhD, director of the UVA Center for Diabetes Technology] developed an algorithm that allows a computer to know how much insulin a patient needs based on continuous glucose monitoring systems,” explains José Oberholzer, MD, director of the UVA Charles O. Strickler Transplant Center. “This computer then triggers the insulin pump to deliver just the right amount of insulin.”
Patients Who Need a Device Alternative
As promising as this technology is, there remains a subset of patients for whom these novel devices are not the best solution to keep their blood sugars in check. According to Oberholzer, UVA is leading the way in addressing the needs of these patients, too.
“These devices are great, but unfortunately, they aren’t perfect for everyone,” says Oberholzer. This is because there is a bit of lag time.
Blood glucose levels are measured in the skin, not in the blood, which isn’t as immediate. So from the moment glucose levels change in the blood to the time insulin can be administered, there is a delay. “For patients who are unstable, a lot can happen in that time, so there is some risk for those who experience lows very quickly,” adds Oberholzer.
This unstable or hard-to-control type 1 diabetes, with extreme swings in glucose levels — from very high to very low — is known as brittle diabetes. Over time, patients with brittle diabetes lose their ability to recognize a drop in blood sugar. Their brain and nervous system become so accustomed to the lows that the body no longer triggers the usual warning signals, such as hunger, an adrenaline rush, sweating, heart palpitations and more. This is known as hypoglycemic unawareness and it impacts approximately 10% of patients with type 1 diabetes.
“These patients lose that safety zone when they can react,” says Oberholzer. “Their blood sugar gets extremely low, and they can get confused or worse, they may have an accident or pass out.”
This increased risk for cognitive dysfunction greatly impacts quality of life; patients may be hesitant to leave home or may require someone to watch them full time. Their prognosis overall is typically not good, according to Oberholzer. “This is the population we’re targeting for transplant,” he says.
Two Types of Transplant to Treat Type 1 Diabetes
The goal of transplant is to replace the insulin-producing cells in the pancreas that are destroyed by the immune system. This can now be done two ways: a solid organ transplant or islet cell transplant.
The standard of care for many years, a pancreas transplant is a challenging procedure, in part, because of the intricacies of the digestive system. “In addition to producing a variety of hormones, such as insulin and glucagon, the pancreas delivers all of the exocrine juices that help with digestion. During transplant, there is a small piece of bowel that has to be connected to the organ recipient for those digestive juices to be secreted,” says Oberholzer. This connection introduces the risk of a leak that can cause peritonitis. Vessels, too, must be connected, so thrombosis and bleeding is another feared complication.
“Fortunately, the success rate for pancreas transplant is very high now, but it can be a difficult procedure for the patient if there are complications. These are rare, but it’s not a zero-risk procedure,” says Oberholzer.
To reduce the risk further, Oberholzer is performing this procedure robotically using a minimally invasive approach — he is the first surgeon in the U.S. and just the second in the world to do so. Rather than making an incision from the pelvis to the chest, this procedure is done using a bikini incision and a small cut for robot access.
“This is technically a very challenging procedure and only a few surgeons in the world are doing it,” he says. “It offers many advantages to the patient, including a smaller scar, reduced blood loss, less pain and a quicker recovery.”
Islet Cell Transplant
Another treatment showing promise as a potential cure for type 1 diabetes is islet cell transplant. As the founding coordinator of the Chicago Diabetes Project, a global collaboration of scientists, researchers, physicians and surgeons working to cure diabetes, Oberholzer has been instrumental in advancing the islet cell transplant program at UVA. It is one of the few centers nationwide with the solid foundation in place, including a skilled team of scientists and advanced labs and equipment, required to facilitate this complex procedure.
Some of the steps involved to acquire and transplant insulin-producing cells include:
- Procuring a healthy pancreas from an organ donor
- Injecting the donated pancreas with an enzyme solution that breaks down the organ until clumps of islet cells remain
- Separating out the lighter islet cells from a cell suspension
- Testing the cell recipient to ensure they are a match immunologically for the donated cells
- Using microfluidic biochips to test functionality of cells in an environment that mimics the human body
- Placing a catheter into the recipient’s portal vein
- Injecting the islet cells into the liver (where all sugar metabolism happens)
- Monitoring to ensure cells aren’t rejected
“Once we transplant those allogeneic cells, they will be foreign to the recipient. The immune system will recognize that and mount a rejection reaction,” explains Oberholzer. “This is why we have to give these patients the same immunosuppression [medications] as we give to an organ transplant or bone marrow transplant patient.”
When it’s clear the new cells are functioning, the patient can slowly wean off of insulin, which takes approximately 10 weeks. If the first injection of cells isn’t effective, additional injections may follow. “After five years, 6 out of 10 patients will not need insulin,” says Oberholzer. “The longest a patient I’ve personally followed has gone without insulin is 15 years, which is spectacular. The goal is to achieve this in more patients.”
Overcoming the Limitations of Islet Cell Transplant
To do so will require overcoming some of the current limitations of the procedure. First being the limited number or donated organs available. The second is the need for immunosuppression. New studies are currently being launched to address these challenges and, according to Oberholzer, UVA will be an active participant.
“One study will test islet cells not isolated from an organ, but created at a lab,” says Oberholzer. “This is the first trial ever done in humans for stem cell-derived islet cells rather than organ-derived islets.”
Another trial is investigating the use of microencapsulation, or putting a protective shell around the islet cells, to protect them from the immune system and eliminate the need for immunosuppression. “We would essentially transplant these encapsulated islets into the abdominal cavity,” explains Oberholzer. “Preclinical models show that those cells function like mini pharmaceutical factories inside the human body; they produce insulin just like a normal pancreas would do.”
“If we can overcome some of the risks and limitations of islet cell transplant, we will be very close to a functional cure,” he says.
Best Candidates for Transplant
Only when a patient is unable to control blood glucose levels and has exhausted all standard disease management options should a physician present transplant as potential treatment option, according to Oberholzer. “Transplant is not a substitute for normal diabetes management,” says Oberholzer. “But if normal treatment fails, this is a viable option. Many patients and physicians are still unaware.”
If you think your patient may be a good candidate for transplant, contact Meaghan Stumpf. A highly experienced transplant endocrinologist well versed in diabetes technology and transplant medicine, she is uniquely qualified to evaluate patients with diabetes for a transplant procedure.
Inclusion Criteria: Transplant for Type 1 Diabetes
- Non-obese or a BMI less than 27 for islet cell transplant (no BMI limit for pancreas transplants)
- Age 18 to 65
- Normal insulin requirements, defined as equal to or less than 0.7 units of insulin per kilogram of body weight per day, for islet cell transplant (there are no insulin requirement limits for pancreas transplantation)
- Suffer from hypoglycemic unawareness or brittle type 1 diabetes
To refer a patient to UVA Health, call UVA Physician Direct at 800.552.3723.