Interview with Dr. Andrew Posselt: Eliminating Type 1 Diabetes with Islet Cell Transplantation

Hear a Patient Power interview with Dr. Andrew Posselt, director of the Pancreative Islet Transplantation Program at UCSF Medical Center.

Islet Cells

Andrew Schorr:

Islet cell transplantation, what does it mean today for someone with type 1 diabetes, and also, other serious conditions? We'll hear all about it from a leading expert next on Patient Power.

Hello and welcome to Patient Power, sponsored by UCSF Medical Center. I'm Andrew Schorr.

Type 1 diabetics have probably heard about islet cell transplantation. It's not done many places, and it's not for everybody, but we're going to find out what they do at UCSF Medical Center, a leading center for this, and also how it may apply to another serious condition as well.

Joining us is the director of the Pancreatic Islet Cell Transplant Program at UCSF, and that's Dr. Andrew Posselt. Dr. Posselt, welcome to Patient Power.

Dr. Andrew Posselt:

Thank you, Andrew. Nice to be here.

Andrew Schorr:

Let's start with this: What are islet cells?

Dr. Andrew Posselt:

Well, islet cells, they're actually not cells. They're islets, and islets are clusters of cells of about a thousand cells that are in the pancreas, and these cells produce various types of hormones, the most important of which is insulin. So, they control blood sugars in all mammals, essentially.

Andrew Schorr:

Right. And when someone has type 1 diabetes, what's gone wrong, and maybe what happened to their islets?

Dr. Andrew Posselt:

So type 1 diabetes is an autoimmune disease, which means that your immune system attacks your own tissues or certain types of tissues, and in diabetes the immune system attacks the pancreatic islets, and it eventually destroys the islets and the patient then cannot make any more insulin and becomes diabetic. That's type 1 diabetes.

Type 2 diabetes is a little different, and that's a condition where the body becomes resistant to insulin. So the islets are making sufficient amounts of insulin, but because of a variety of reasons like obesity and so forth that's not enough for the patient to maintain normal blood sugars.

Andrew Schorr:

Now, of course when someone has type 1 diabetes they become insulin dependent, right?

Dr. Andrew Posselt:

Mm hmm.

Hypoglycemic Unawareness

Andrew Schorr:

They need insulin given to them. But I also understand that some of them can develop a condition called hypoglycemia unawareness, quite serious. What is that?

Dr. Andrew Posselt:

Hypoglycemic unawareness is really a condition that results from having longstanding diabetes, type 1 diabetes, when someone is without insulin they obviously have to give themselves insulin through shots, and over time even if control is good, there's going to be some periods of time when the sugar has really dropped down really low, sometimes they're high, and this fluctuation in blood sugars makes the body less sensitive to low sugars. You kind of get used to it. So, as this condition worsens patients can have blood sugars drop down to very dangerous low levels, and they might not sense it. And sensing it, meaning they don't become dizzy or tremulous or feel nauseated, things like that. They just don't feel anything.

Andrew Schorr:

And that could be an emergency.

Dr. Andrew Posselt:

Yes, because you can potentially die from having too low blood sugar without even noticing it, and that can happen when you're asleep and so forth.

Andrew Schorr:

You have patients, and have had patients with that condition, type 1 diabetes, they get to this hypoglycemic unawareness and then you start talking about, well, what can you do?

Dr. Andrew Posselt:

Correct.

Islet Transplant

Andrew Schorr:

Tell us about islet cell transplantation, where that fits in, and also compare it with some other approaches like transplanting a pancreas.

Dr. Andrew Posselt:

The beauty of islet transplant or pancreas transplant is that you're really replacing the cells that are missing in diabetes. It's not like giving just insulin or using an insulin pump to give you insulin at a continuous rate. Replacing the cells allows your body to regulate blood sugars in a very normal way. So, if the blood glucose level drops down really low the cells turn off insulin production and they produce more glucagon, which can bring your blood sugars up. If your blood sugars go high they can make more insulin, and they can control it very precisely.

Islet transplant developed, sort of, as a less invasive way of giving islets to patients with type 1 diabetes — less invasive meaning you don't need surgery. These islets, after they're isolated they're very pure and the volume of the total islet infusion, that you give to a patient, is, maybe, like an ounce or so of fluid of cells, and they're infused into the portal vein of the liver so they are — a radiologist introduces a needle into the liver and then the islets are just dripped in into the bloodstream and to the liver. It doesn't require any open surgery or general anesthesia or recovery from surgery.

Andrew Schorr:

All right. Where do they come from?

Dr. Andrew Posselt:

So the islets are procured from donors, organ donors, just as other organs are procured. And they're procured from — the pancreas is removed from the donor, brought to a special lab, and it goes through, sort of, a pretty involved process of isolating the islets and removing them from the rest of the pancreas, and then purifying them further, and then they're given back to the patient.

Andrew Schorr:

How much experience does your center have in this? I know it's not done everywhere, that's for sure.

Dr. Andrew Posselt:

I think the biggest hurdle to being a successful islet transplant center is being able to produce good quality islets from the organs that we receive, and we're really good at that. We've been doing it for, boy, I'd say about 15 years or so, but I think over the last 10 years we've really perfected the procedure and we've taught a lot of other centers how to do it throughout the world. But I think it’s a very complicated process. It requires a lot of experience to be able to figure out when you're going to get islets, when not, and so forth, so it's very involved.

Andrew Schorr:

Dr. Posselt, someone receives it. Like any foreign material, if you will, their body might try to reject it, so I imagine, going forward then, the hope is they will need less insulin externally or no insulin for some extended time. What should the expectation be there? And what other medicines do they need to take to lower their risk of rejection?

Dr. Andrew Posselt:

The expectation is that the patient will be able to come off insulin, and the vast majority of our patients have come off insulin. Now, sometimes they need more than one transplant, which is done exactly the same way and is actually easier to tolerate than the first one, but the goal is to get them off insulin.

Currently the longevity of insulin independence after islet transplant is almost as good as that of pancreas transplant, meaning let's say after five years, after islet transplant, about 50 to 60 percent of patients will be insulin independent, and that's about the same percentage of patients who remain insulin independent after pancreas transplant. That's a big improvement from results in the past, and I think that was one of the issues that islet transplantation had to deal with. Patients did not remain insulin independent for as long as they do after pancreas.

Andrew Schorr:

All right. And can you repeat a transplant? It sounds like you can. So now it's five years later, somebody could have another one.

Dr. Andrew Posselt:

Yes, it's very easy to do that. We've had patients who have had three, and they're doing great. Again, it's much easier to do than repeating a pancreas transplant.

Andrew Schorr:

I would imagine. Now, I alluded to, though, antirejection medicine, so tell us about that. So how does somebody go on with their life?

Dr. Andrew Posselt:

You know, since you are transplanting an organ from another patient there is a risk of rejection, so patients do need to take immunosuppressive medications. And the medications they take are essentially the same as they would take for any other organ transplant. The medications we use nowadays are very well tolerated. They do have some side effects, but they're pretty minimal, and patients really can lead a completely normal life afterwards. They do need to take the meds, but I don't think it impacts their lifestyle at all, or their health.

Chronic Pancreatitis

Andrew Schorr:

Now, I understand that your center is, also, doing a type of islet cell transplantation for another condition, pancreatitis. What is pancreatitis, and what type of transplant do you do there?

Dr. Andrew Posselt:

So pancreatitis, it's actually there are different types of pancreatitis, but the pancreatitis that we do islet transplants for is called chronic pancreatitis. And chronic pancreatitis is a longstanding disorder of the pancreas, and it's caused by a variety of different issues such as gallstones or it can be inherited or there may be some anatomic abnormalities. But basically what happens is the pancreas shrivels down, is not doing its job of digesting food any more, and because there's abnormalities within the organ it's very painful.

The main problem with chronic pancreatitis is severe pain, and these patients need a lot of pain medications. Their lives are very debilitated because of this, and in the past people have tried to inject the nerves around the pancreas or do some surgery on the pancreas to try to relieve the pain, and none of these approaches have been that effective. So, relatively recently, the thought was to remove the whole pancreas and see if that helps the pain, and it's actually very effective in helping the pain. But if you just remove the pancreas, then you will be stuck with a patient who has very severe diabetes, because you're also taking the islets out, and having no islets at all makes them essentially the same as a type 1 diabetic.

What we, and some other centers, are doing is, after the pancreas is removed, we process it the way we would other pancreases and isolate the islets, and then give those back to the patient. And that's done all at the same day during the time of the surgery, so there's no extra surgery involved, and that allows the patient to, either have no diabetes at all, or have very mild diabetes that's easily controlled.

Andrew Schorr:

Let me see if I understand that. So you've removed their pancreas, you've taken their own islet cells, and you've given the islet cells back. Now, where do the islet cells go if they're normally in the pancreas?

Dr. Andrew Posselt:

We put them in the same place as we do the other types of islets. We put them into the liver. We just inject them into the portal vein, which is the big vein that flows from the intestines into the liver, and they go into the liver and they lodge in the liver itself, and then they establish a blood supply and start working.

Andrew Schorr:

All right. So just to differentiate, in the case of type 1 diabetes these are donor islet cells because the type 1 diabetic doesn't have any of their own. In the case of pancreatitis you are giving them back their own islet cells.

Dr. Andrew Posselt:

Correct.

Andrew Schorr:

Okay. So, this must be very gratifying for you to be developing this and seeing it benefit patients.

Dr. Andrew Posselt:

Oh, absolutely, yeah. It's been amazing watching some of these patients who are really debilitated by their diabetes. For example, they can't drive because they don't know when their sugars are going to drop. They've had multiple episodes of being woken up in the middle of the night by their loved one because they look like they're going into a coma, and really not being able to lead a normal lifestyle, and getting this relatively noninvasive procedure and then, really, just being cured of their diabetes. It's been very gratifying, yep.

Andrew Schorr:

And in the case of pancreatitis, relieving the pain and coming up with, really what sounds like, a pretty innovative solution.

Dr. Andrew Posselt:

Yeah. Yeah, and these patients, again, they're very debilitated, and the majority of these patients, after the removal of the pancreas and the islet transplant, can completely come off their pain meds. So, they can really become pain free.

The Future of Islet Cell Transplantation

Andrew Schorr:

Wow. So, Doctor, with this whole field of islet cell transplantation, whether it's from a donor or whether it's your own, where are we headed with this? First of all, will we be able, in the case of getting someone else's cells, maybe, to even lower the need for antirejection medicine and other refinements to the procedures? Where are we?

Dr. Andrew Posselt:

Well, there are a number of paths that people are taking who are working in this field, and obviously, the first thing that we need to try to accomplish, and I think we're very close, is to really improve the efficacy of the islet isolation process. Currently people estimate there are about a million islets in a normal pancreas, and if we perform a really good isolation, we obtain, maybe, 500 or 600,000 islets, high quality islets. So, we're getting pretty good at isolating all of them, but not quite there yet.

And, I think, if we are able to isolate more islets more efficiently and make sure they are top quality, in terms of the health of the islet, then that will help us a lot to be able to transplant more patients because, currently, most patients need two transplants and there's a lack of donors, it makes it more difficult. That's one issue, improving the efficacy of the islet isolation.

The other one is immunosuppression, as you mentioned. I think you know this is, sort of, a hurdle that involves all of transplantation, since all patients need to take immunosuppression after transplant. Islets are a little tricky because they're not — once they go into the liver you can't find them again, so there's no way to tell, by doing a biopsy or something like that, whether they're being rejected or not, so if rejection happens it can go all the way and destroy all the islets before you really know it before the patient becomes diabetic again. They do need to take immunosuppression, and there's a lot of drive to find more effective but less toxic immunosuppressive drugs, such as various antibodies and so forth.

And, maybe, down the line, we will be able to figure out how to make someone tolerant. And, in fact, we have one patient that we transplanted with islets about five years ago, I would say, and for a variety of reasons she ended up coming off immunosuppression, and she's now been off all immunosuppression for almost a year, and her sugars are completely normal and her islets are working well. We don't understand how this happened, but it shows you that it is possible.

Andrew Schorr:

So, looking to the future, for people with type 1 diabetes, who are listening or maybe people with pancreatitis who are at their wit's end, would you say there's a great deal of hope that this technology and the skill can be refined more to give them even greater benefit?

Dr. Andrew Posselt:

Absolutely. Yes. Definitely.

Andrew Schorr:

It sounds like you're a leading center. If someone is listening, you're certainly open to consultations to see whether this is right for them.

Dr. Andrew Posselt:

Correct. Yes.

Andrew Schorr:

Well, I want to congratulate you for all the work you've done to this point, and the difference you've made in people's lives. I was reading a story about a dancer who is, as you said, you know, not insulin dependent anymore, and she leads a pretty normal life, and I know she's dancing up a storm. So as you said, that makes you feel great.

Dr. Andrew Posselt, the director of the Pancreatic Islet Cell Transplant Program at UCSF Medical Center, thank you so much for being with us and your devotion to patients.

Dr. Andrew Posselt:

Thanks so much for having me.

Andrew Schorr:

All right. Very positive medical story, and it continues to evolve to help people with type 1 diabetes, and as you heard now another condition, chronic pancreatitis.

I'm Andrew Schorr. Thank you for be listening. Remember, knowledge can be the best medicine of all.

This interview was recorded on May 10, 2013.

 

Reviewed by health care specialists at UCSF Medical Center.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.

Related Information

UCSF Clinics & Centers

Endocrinology

Diabetes Clinic at Parnassus
400 Parnassus Ave., Suite A-550
San Francisco, CA 94143
Phone: (415) 353–2350
Fax: (415) 353–2337

Diabetes Clinic at Parnassus
400 Parnassus Ave., Suite A-550
San Francisco, CA 94143
Phone: (415) 353–2350
Fax: (415) 353–2337

Condition Information