Jose Oberholzer MD, director of the Chicago Diabetes Project provides his insights when he consults patients through the various stages of having an islet cell transplant.
 
By: John Parkinson, Clinical Content Coordinator, DiabetesCare.net

Waiting for the phone call. Islet cell transplant recipients often speaking of waiting for the go-ahead to prepare themselves for going to the medical center to have their transplant performed as one of the most difficult and exciting times during the transplant process. There are moments of trepidation and others filled with the hopeful joy of thinking about what may lie ahead after a transplant.

The surgeons are also waiting, because there is limited availability of islets as their only source is pancreases from cadavers.

Waiting for a suitable donor can mean there is a lull between procedures that limits their ability to help more type 1 patients. This is one of the biggest frustrations for Dr. Oberholzer who performs these procedures. 

As director of the Chicago Diabetes Project, Dr. Oberholzer and his team are investigating ways to grow islet cells.

In addition to his work on the Chicago Diabetes Project, Dr. Oberholzer (pictured, lower left) is a Professor of Surgery, Endocrinology and Diabetes, and Bioengineering at the University of Illinois at Chicago (UIC), the Director of the Islet and Pancreas Transplant Program, and the Chief of the Division of Transplantation at the University of Illinois Hospital.


Still many of the patients who have gone through the entire islet cell transplant process are excelling and remain insulin-independent for years. It is important to provide an understanding of what the process entails; therefore, DiabetesCare.net spoke to Dr. Oberholzer about what it is like to walk a person through the transplant process from the clinical criteria for prospective patients, to the challenges associated with the transplants, and the expectations for potential outcomes post operatively.

DiabetesCare.net: When talking with prospective patients, what is the criteria you are looking for in determining if they would be a good candidate for islet cell transplantation?
 
Oberholzer: When seeing if someone is suitable, the first question I have to ask is does the patient have a problem that would justify some risks? With someone with perfectly controlled diabetes, I would not consider the person for treatment.
 
The most common problem where we can justify the risks for the transplant and the immunosuppressant drugs is hypoglycemic unawareness. Luckily, it is not a very common condition.
 
We will try to treat the patient conservatively first. We will put him or her on a pump, and glucose sensor, but in most cases when they have hypoglycemic unawareness, the only way to treat them is to do a pancreas transplant or an islet transplant.
 
We are not seeing this as frequently but occasionally we will get a call from a patient’s ophthalmologist, who is seeing someone who has rapidly progressing diabetic retinopathy. In these cases we will do a pancreas or islet transplant. For those who are suitable, I would rather go for an islet as opposed to a pancreas procedure.

DiabetesCare.net: How do you decide when a person is a better candidate for a pancreas or islet cell transplant?

Oberholzer: An islet cell transplant cannot offer as many islets as a pancreas, because in the process of isolating the islets you lose a percentage of them.
 
If someone is obese or has high insulin requirements, then an islet cell transplant is going to be difficult. In those cases, I would opt for a pancreas transplant. And the opposite applies for whom I would consider a candidate for an islet transplant.
 
Generally, we calculate how many units of insulin a patient needs per day and then we divide it by the body weight.
 
Islet cell transplantation is an experimental procedure and can only be offered with the framework of a clinical trial, and in these, there are inclusion and exclusion criteria. Even if someone presents with the aforementioned criteria, there may be reasons within the trial parameters that they cannot fit the protocol.
 
Reasons for exclusion might be reduced kidney function or tissue sensitivity or maybe there are other reasons outlined in our FDA-approved protocol.
 
DiabetesCare.net: How do you characterize islet cell transplantation when you speak to a patient about the surgery? Is it a cure? A remission of symptoms? Both?
 
Oberholzer: When I talked to patients about the procedure, I talk about it being a “functional cure.” This means from patients’ perspectives, they will feel like they no longer have diabetes. Their blood sugars will be normal; they won’t have to inject insulin; and so in that way, they are cured.
 
The reason I tell them they are not cured from a traditional standpoint, is if they reject the transplant, they will be back to being diabetic. We can reproduce the function of the insulin producing cells, but the transplant cannot eliminate the underlying disease.
 
As long as they take their immunosuppression medicines, most patients will be safe from their diabetes. However, if for some reason they don’t remain on their medication regimen, or their immune system gets activated, they may lose the transplant. 
 
DiabetesCare.net: Speaking of immunosuppressants, it was recently reported that Rapamycin, a drug used for transplant and cancer patients, has been blamed for causing diabetes-like symptoms. Have you used it for transplant patients? What is the post-op regimen prescribed for islet cell transplant recipients? 
 
Oberholzer: You start off with a higher level of immunosuppression and then you taper the amount of the regimen later through the process. In the beginning we perform induction therapy and we use an antibody medicine. There are various drugs you can use. Our post-transplant regimen includes Prograf (tacrolimus) and Rapamycin (sirolimus).

Rapamycin is a complicated drug, but it has been a major contribution to the success of islet cell transplantation. Not all patients will tolerate it, and in those patients, we go to an alternative drug that we use called MMF. 

The side effects of these medications can go from almost nothing to the point where a patient has to be taken off of them. The vast majority of patients tolerate them very well. I think it is a bit of a misconception that is out there about Rapamycin. Some people may think it is terrible, but if you talk to our patients, most of them have been taking it for years and don’t feel any effects.

DiabetesCare.net: Is there a medical metric or criteria to measure people on these immunosuppresants?

Oberholzer: We monitor the graft function and the blood sugar levels in the body. On a regular basis, we do metabolic tests, like an oral glucose tolerance test, just to make sure their glucose function is still normal.

In addition to those tests, we do monitor the immunosuppresion drug levels. Those medicines have to be titrated to reach a certain level because we don’t want to give too much and reach toxicity or give too little and the patients reject the transplant. We have to find the right balance.

In the blood work, we monitor for potential side effects, and we look for things like a low white blood cell count or kidney dysfunction.

DiabetesCare.net: Can you take me through what islet cell transplant recipients do post-op in terms of their care including which medical providers they see and how often?

Oberholzer: At the CDP, we do all the post-op care and collaborate with their primary care physicians. In general, we see more of the patients in the beginning, and then gradually less and less, once the risk of losing the transplant lessens.

In the first two weeks post-op, we will see them three times a week. Then we will see them twice a week for two weeks. Then we will see them weekly up until three months post-transplantation.

After three months, we will see them on a monthly basis. Once they go beyond the first year, we will see them every three months.  We will continue to do that for as long as the islet cell transplant works and they are on immunosuppression medications.

We will go through their glucose readings and there are educational aspects including how to take the medications and lifestyle issues, like dietary recommendations.

We answer any questions the patients have and go through general post-op recommendations on how to handle lifestyle situations.

DiabetesCare.net: Do you have a diabetes educator on staff who sees the patients post-op?

Oberholzer: Post-op, the patients generally don’t have diabetes, but patients may have questions about their diets. We offer any medical support a patient may need. We want them to remain as close to a diabetic diet as possible. Sometimes there are questions that a dietitian can answer.

We also have other support such as social workers or psychologists available to address mood change issues or related problems.

DiabetesCare.net: Can you provide some data on the surgical outcomes in terms of long-term transplant patients? Success rates? Anything to provide a sense of the efficacy of the procedure?

Oberholzer: At present, we can get almost everyone off insulin. In our present trial, we are approaching 30 patients. We have had only one patient who lost their islet transplant within two weeks of the operation. At one year after transplantation, 8 out of ten patients are off insulin. Therefore, we have an 80 percent success rate after one year. And at five years, 60 percent of our patients remain insulin-independent.

Diabetescare.net: How many transplants have you performed?

Oberholzer: Here in Chicago, we are approaching 30 patients. I believe we are at 28 total. In my previous experience in Geneva, I believe we were close to 50 transplants. Additionally, I was in Edmonton for a brief period, where numerous patients were transplanted.

While these are not huge numbers, I’m likely to be considered as someone who has performed more transplants than most surgeons who are doing the transplant world-wide.

DiabetesCare.net: What are the biggest learning curve elements for patients post-transplant?

Oberholzer: One of our researchers explained it very well when she said, ‘we are helping them to perform a transformation of their bodies.’ They go through a dramatic change where most of it is good, but some of it can feel unsettling at first. For example, for many of the patients who have diabetes, their nerves don’t operate or feel normal. Some patients post-op regain feeling in their feet and their nerves begin tingling when they start to regain the feeling. Other patients say their taste buds change. They didn’t realize their sense of taste was reduced, but then they start tasting things they didn’t before.

The biggest aspect that is most impressive to see is that these patients learn to regain confidence. Most of these patients had lost their confidence because they were scared they would have a severe low. These patients would always have someone with them to avoid this. And now post-op, they realize they can exercise and do things without having to worry about going low.

It takes some time to adjust to this; it is like a regained liberty. One of our patients wrote that she felt like she was in prison when she was diabetic, and now we let her out, and she had to relearn what it was like to be free.

This is the second installment in a two-part interview. In the first installment, DiabetesCare.net spoke with Dr. Oberholzer about the Chicago Diabetes Project’s islet cell research and its transplantation ambitions for the future. That story can be viewed here.