Shireen: In today’s episode, we sit down with Dr Melena Bellin to discuss chronic pancreatitis. We discover its symptoms, risk factors, its connection to diabetes as well as Islet transplantation. If that term is new to you, stick around, it’s mighty fascinating.

Dr Melena Bellin is a physician and professor of pediatric endocrinology at the University of Minnesota and the University of Minnesota Masonic Children’s Hospital. She has an active clinical research program focused on diabetes and pancreatitis. She serves on the board of directors for the National Pancreas Foundation and on the Council for the American Pancreatic Association. Welcome, Dr. Bellin.

Dr. Melena Bellin: Thank you and thank you for having me an absolute pleasure.

Shireen: Dr. Bellin. I wanna first kick things off by just asking you and if you wouldn’t mind sharing with our listeners a brief journey of how you got started in providing care for children with general endocrine disorders. And then I also want to understand what led you to pursue this research in treating chronic pancreatitis.

Dr. Melena Bellin: Right, so, I am a pediatric endocrinologist training. And so for those who may not be familiar with pediatric endocrinology, that means I’m a pediatrician who specifically cares for children who have hormone disorders. So the most common things we see in our clinic are diabetes, usually type one diabetes in children and then children who may have disorders of growth or thyroid function.Those are some of the common disorders we treat. 

I went into my medical training, wanting to be a pediatrician. I wanted to work with children. and endocrinology was a topic that really grabbed me during my education and training. It’s really a a rewarding field to be able to take care of these children who have chronic lifelong conditions that are very manageable. And we can provide care for them to live and thrive normally. 

One of the things that happened while I was in training is that I started to work with this very unique group of children from the diabetes perspective. So there is a, a group of children that we see from all across the country here at the University of Minnesota who have a condition that we’ll talk about today called chronic pancreatitis.

And, the kids usually have it because they have a genetic condition that they’re born with that predisposes them. But very briefly, these kids were in the hospital repeatedly with pain from this pancreatitis. And, the treatment that they needed was to surgically remove the pancreas. And a very specialized part of that is to take the islets out of the pancreas, which we’ll talk about and put them back into the liver and islet auto transplant.

So I started seeing these kids to manage their diabetes associated with that. But then what I saw was the condition of chronic pancreatitis. It’s, it’s so challenging to treat and and surgically removing the pancreas is the probably the most extreme thing we do for this condition. But it can just completely transform the lives for these children in terms of getting them back to school and normal function.

So I was really drawn into the pancreatitis field from that diabetes side. But, but I, I like to call myself a, a diabetes pain creatologist. So I actually deal with both the digestive pancreas, pancreatitis and diabetes now. And my research is heavily focused in the pancreas.

Shireen: So I find that I find that fascinating Dr. Bellin. So let’s take a step back. And before we dive into chronic pancreatitis, help us understand what the pancreas is. What is the function it serves?

Dr. Melena Bellin: Right, so a lot of people don’t think a lot about the pancreas unless they have a problem with it., but it’s a really essential organ. It’s in our abdomen, it sits behind the stomach and it has two major components. So it has a digestive part that’s about 98% of the pancreas is a digestive part. So that digestive pancreas, which we also call the exocrine pancreas, iIt makes digestive juices that are squirted into the gut essentially, when you have a meal, those digestive juices go into the intestine. They help us digest our nutrients, particularly fat and protein and absorb the food. 

And then the other part of the pancreas, the other 2% of the pancreas is what we call the islets. So, eyelets are clusters of cells that secrete hormones, including insulin. So, insulin specifically comes from a cell type called the beta cell within the islets. And so when that food gets absorbed into the system and the sugar in the food, particularly the carbohydrate hits your bloodstream, that signals the islets to put out this insulin hormone, insulin helps us use the sugar from our food and take that sugar up into muscles and fat cells to give us energy and nutrients.

So those parts kind of they, they work together, they’re very complementary. But what’s interesting on the medicine side is that they’re managed by completely different groups for the most part. So, gastroenterologists manage the digestive pancreas and endocrinologists manage the diabetes part, the islet part of the pancreas. 

Shireen: Interesting. And so now diving into chronic pancreatitis, help us understand what that is and how does it differ from acute pancreatitis.

Dr. Melena Bellin: So, acute pancreatitis is more common than chronic pancreatitis. So when someone has an a pancreatitis in general, they have inflammation of the pancreas. And acute pancreatitis, that’s an inflammation of the pancreas that comes on very suddenly. It’s usually at a temporary condition. It can be quite, quite painful. So people with acute pancreatitis will present with very severe upper abdominal pain.

Oftentimes associated with vomiting, they’ll oftentimes be so sick that they end up in an emergency department and oftentimes will need to be hospitalized for a few days and sometimes in more severe cases, even a few weeks. And that inflammation, ideally in most cases resolves. And for about 90% of patients who have an episode of acute pancreatitis. It’s a one time deal. 

One of the common factors that predisposes people is having gallstones. So if they have gallstones, they might have their gallbladder surgically removed, we might have what we call idiopathic acute pancreatitis, which means we don’t really know why that happened. But for most people, it’s one time and it never comes back, never occurs. So which, which is wonderful. That’s, that’s what we hope for. 

Unfortunately, for a smaller proportion of patients who have acute pancreatitis, they go on to get either recurrent episodes of acute pancreatitis or chronic pancreatitis or both. And so, chronic pancreatitis can actually be a little bit trickier to diagnose because even with our really good imaging studies of the pancreas like CT scans and MRI scans, it can be hard to see that chronic damage until it’s very advanced or late stage. 

But what chronic pancreatitis is is that that acute inflammation has become more chronic and there’s scar tissue and damage to the pancreas. So, patients who have chronic pancreatitis, sometimes they actually can do quite well and not have a lot of symptoms of their disease. But oftentimes what they present with is having frequent episodes of pain, some that are very severe like acute pancreatitis where they need to be in the hospital and some that are manageable at home, but can still be really debilitating, can make it hard for some patients to be able to sustain a normal life, like going to school for kids or working for adults or simply even spending time with family or going on vacation. 

So it can be a really difficult chronic disease for some patients to live with for chronic pancreatitis. And because it’s not easy to see on imaging, a lot of these patients will sometimes get almost mistreated when they go to the hospital, not because of poor intentions on the part of the medical providers. But because it can be hard to see that chronic pancreatitis, sometimes people get told, well, they must not really be in that much pain or it must be in their heads. So there’s this whole other kind of psychosocial element that’s difficult in chronic pancreatitis and that it gets misunderstood and sometimes not managed that well because it is really difficult to measure that chronic pancreatitis and to measure that pain that individuals are having.

Shireen: And so having said that what are some common symptoms, you mentioned the pain, what else would someone look for for something like that?

Dr. Melena Bellin: Yep. So, so the earliest symptoms are the pain. So typically patients with chronic pancreatitis will first present with this recurrent abdominal pain and sometimes that will also be associated with nausea or vomiting. Sometimes, but not always that pain can be really triggered by food. If you think of it when you eat, that’s what’s triggering the digestive pancreas. And what pancreatitis really is, is inflammation of that digestive part. So sometimes when you stimulate that digestive part of the pancreas, those symptoms get worse. 

But as the scarring part of the chronic pancreatitis progresses and the pancreas gets more and more damaged over time at that point in time, unfortunately, it can do so much damage to the functional parts of the pancreas that people can start to have problems digesting their food. So we’ll call that exocrine pancreas insufficiency or exocrine pancreas risk dysfunction. So people will abbreviate that EPI or EPD. But that essentially means your digestive pancreas is not making enough of those digestive juices and enzymes to be able to process the fats and proteins in your food well, so that can be one later complication. And then people can start to have diarrhea, fatty greasy stools, other symptoms that come with malabsorption. 

The other late complication that we oftentimes see and again, it usually occurs years into the disease. Sometimes decades is development of diabetes. So the inflammation from pancreatitis is actually in that digestive part, I talked about the two parts of the pancreas and the inflammation is in the digestive part, but what can happen with that inflammation and scarring is because that, that endocrine part, the islets are sort of scattered throughout the digestive tissue that scarring starts to destroy some of those islets that make the insulin as well. 

So over time, people make less and less insulin and they develop a form of diabetes that has some similar features to type one and sometimes even some similar features to type two diabetes. But many of those patients end up needing insulin therapy for treatment. And so before they’re diagnosed, they might also present with weight loss from diabetes. They may have symptoms of going to the bathroom more often or being more thirsty, which are general symptoms of high blood sugar.

Shireen: Interesting. And I do want to unpack a little bit about this relationship with diabetes. Before we go down that road though, can you talk to us some of the talk to us a little bit about the risk factors associated with the development of chronic pancreatitis and how can one go about mitigating some of the risks associated there?

Dr. Melena Bellin: Yeah, that’s a really excellent question. And it’s tricky because we don’t entirely know what all of the risk factors are. So we know that alcohol and smoking can be risk factors for chronic pancreatitis. But I want to be careful in how I say this because one of the big misunderstandings in medicine is chronic pancreatitis was originally described as a disease of people who had alcoholism and were very heavy drinkers.

And there are some people who get chronic pancreatitis because they have a very heavy drinking history. But that’s really the minority of patients. And so that’s a stigma associated with chronic pancreatitis for, for some medical providers to automatically assume that someone might, might be drinking or have an alcohol disorder most of the time, that’s not the case. But that being said, once someone has chronic pancreatitis, we know that alcohol can irritate the pancreas. 

So once they have the disease, we do recommend refraining from drinking alcohol to not exacerbate the disease or cause further damage. And what turns out in the recent literature to be even more important is actually smoking, smoking can cause even worse progression of chronic pancreatitis than drinking alcohol. 

So tho those are modifiable risk factors that people can address the other stuff is very tricky. We have a lot of people who have what we call idiopathic disease, meaning we don’t, we don’t know why. And very importantly, we don’t then know what they can do to prevent that or reduce the progression of that. And then we have people who have gene mutations that affect the way the digestive pancreas works and as a consequence of that give them episodes of acute and pancreatitis leading to chronic pancreatitis. And we don’t have any genetic directed treatments unfortunately, for chronic pancreatitis. So for those individuals with genetic disease, we we don’t honestly have a lot to offer yet in terms of something that will prevent or halt that disease process.

This is a really, really important component of some of the research that’s going on now in in the United States. So the National Institute of Health which sponsors a lot of research in the US has really increased their funding for pancreatitis based research in the last decade. And so as the Department of Defense, actually, which funds a lot of medical research. There are two study consortiums that are formed by the National Institute of Health right now that are looking at pancreatitis, both acute and chronic pancreatitis and the progression of those diseases, both in terms of pain symptoms, but also in terms of things like diabetes and exocrine insufficiency and the goal of those study consortiums long term is really to understand this disease process better so that we can target early intervention so that we can prevent that progression. But right now, I will say it can be difficult for patients because what you can do on the patient side can be a little bit limited.

Shireen: And so speaking of which, can you help us understand how does chronic pancreatitis really affect digestion and nutrient absorption? You mentioned some damage happening there and then what dietary modifications are recommended to manage some of those challenges.

Dr. Melena Bellin: So when we talked about that exocrine pancreas insufficiency, or exo pancreas dysfunction, that is that condition where the pancreas is so scarred, it’s not making enough digestive juices, that is something we can test for. So we can do stool tests that will tell us is the pancreas making enough digestive enzymes or not. And if it’s not, then we can actually give pills with food that replace those digestive enzymes.

So it’s really important to actually for someone who has pancreatitis to be screening that stool study at least once a year to look for dysfunction of the exocrine pancreas. So that we can provide those enzymes with food so that your body can process and digest and absorb the nutrients that you need. That’s particularly important for fat and protein. So that’s one, that’s one consideration on the dietary side. 

The other is a little bit more individualized. Some patients find that certain foods will trigger their pain symptoms with pancreatitis oftentimes that’s fatty foods for many people that will trigger pain symptoms. So some patients with pancreatitis will eat a low fat diet. That’s not everyone. There are patients who find that it doesn’t make a lot of difference to them whether or not they’re eating low fat food and they may not need to modify their diet as aggressively. And there are some patient populations like children where we try to avoid fat restriction because it’s really important. It’s important nutrients for growth. 

So the, the other aspect in terms of dietary adjustments can be very individualized, but there certainly are some patients who benefit from restricting some of the higher fat greasier foods in their diet to, to create less pain flares helps more with the symptoms, less so with the progression of the disease, but can help with the symptoms.

Shireen: And I do want to get back into the connection that we made with diabetes just a couple of minutes ago. Essentially, what we know is that a quarter to all the way up to 80%, which I find that variation quite stark, but in that range of people, with chronic pancreatitis will develop diabetes due to their condition. And of course, you, you talked about their relation there. Can you help us understand a little bit more around those underlying mechanisms by which chronic pancreatitis can lead to the development of diabetes. How quick does that happen or or not happen? Can you walk us through some of that?

Dr. Melena Bellin: Absolutely. You’re right that if you look at the studies that are done right now, the, the the prevalence or how frequently an individual with chronic pancreatitis will get diabetes is wildly different depending on the study. And that’s probably because they have different patient populations in terms of the disease process and what treatments they’ve had.

But we do think that anywhere between, you know, a quarter, 1 out of every 4 to 3 out of every four individuals with chronic pancreatitis is gonna develop diabetes at some point in their life. You have a genetic, a very strong genetic factor that is probably on the order of about 75% risk. Long term. That process of progressing to diabetes is highly variable, but oftentimes takes years to decades. So diabetes is oftentimes a late stage consequence of, of the pancreatitis. 

There are differences depending on the individual. So there are some risk factors that have been identified that have to do with the disease process itself and how it’s treated. So, some people will have various surgical treatments for chronic pancreatitis and generally someone who’s had a pancreas surgery, especially if it removes some of the pancreas tissue is going to be at higher risk.

Or if someone has had a very bad acute pancreatitis that we call necrotizing pancreatitis that actually kills off some of the pancreas tissue. They’re at higher risk and people who have very advanced scarring where we actually see calcium deposits throughout their pancreas, we call it calcific pancreatitis are at higher risk. 

But there are some other risk factors too. We do, we do see that people who are, obese or overweight. but particularly obese and those individuals who have a family history of type two diabetes are at higher risk. So that probably is just something that tips them kind of over the edge into developing diabetes when they have pancreatitis. And some of that might be modifiable in terms of maintaining a healthy body weight. 

When someone does actually get pancreatitis from what we know right now, the main issue is likely just not making enough insulin. So it’s an insulin secretion problem because of the scarring, damaging the eyelet portion of the pancreas. The pancreas is not able to make as much insulin to control blood sugars as it did when it was healthy. So over time, the pancreas makes less and less insulin, but there are probably some other factors that are variable between individuals. And so those individuals who are particularly overweight or have a family history of type two diabetes probably have other risk factors for type two diabetes that then kind of predisposes them to being at more risk of getting that pancreatitis from chronic pancreatitis. 

So it’s a little bit, but those are, those are kind of some of the factors that we know right now, the things that we’re looking at more closely are specific genetics. So there’s genetics that have been identified as risk factors for the more common forms of type one and type two diabetes. And then there’s some interest in looking at some of those genetic risk factors and how they might play into diabetes related to chronic pancreatitis as well.

Shireen: You mentioned within the pancreas, the islet itself. And I want to get into that a little bit. Your research in fact, focuses on islet transportation. What is this concept behind islet transplantation? So first explain that to us, and then how does it differ from other treatment options like a whole pancreas transplantation? So how is this different?

Dr. Melena Bellin: Yeah. So the, let me start with just talking about how these patients are treated because the surgery part, the islet transplantation part is kind of the last step in the road oftentimes. And so when these patients present with chronic pancreatitis, usually our first treatments are symptomatic management. And that’s so that might include IV fluids, either in the hospital or in outpatient setting, making some of those dietary adjustments. If they help putting someone on pancreatic enzymes, if they’re insufficient, might help and doing something we call endoscopic therapy. 

So some of these patients will have their pancreatic duct, which is actually the digestive part of the pancreas where the secretions run through. Sometimes it will get obstructed by a stone or multiple stones in there or an area, area that narrows that we call structure. So some of our gastroenterology colleagues or GI colleagues can go in there with a special scope that helps clear out the stones or remove the obstruction. So those are, those are sort of our cornerstones of management medically and procedurally for patients with pancreatitis. 

But as I said before, there’s not really a curative disease and those treatments have limitations. And so some individuals go through all of those appropriate treatments and then they still have really severe pain and they’re still in the hospital and they’re still unable to work or attend school and we need to offer them something else. And that’s where we start thinking about pancreas surgeries. And there are a few different types of pancreas surgeries that can be done depending on the anatomy of the pancreas and the disease process.

But one of the surgeries that we do and, and where I specifically focus in some of my clinical research, work is the surgery that you were talking about, which the full name for it is total pancreatectomy with islet auto transplantation or TPIAT. Some people will say TPAT, TPIAT or TPAT for that, that name of that surgery. 

And essentially the concept is that to try to get rid of that severe pain, we can just simply take out the pancreas with surgery. And I say simply, but it’s not, it’s not simple, obviously, but that’s the idea there is that we’re removing or resecting the thing that’s causing the pain. The, the, the one of the consequence of that is that you lose all of those islet cells, those cells that make the insulin when you take out the entire pancreas. So if someone does what we call a total pancreatectomy alone, we have really a fully, you know, surgical form of type one diabetes where people are entirely dependent on taking insulin and it can be a difficult form of diabetes to manage. 

So one of the things that we want to do is try to get, rescue as many of those islet cells and get them back to the patient. So that’s the part that we can call islet auto transplantation or the IAT part of the procedure. So this is highly specialized. We have a laboratory facility at our center at the University of Minnesota that actually developed this, this procedure of TPIAT back in 1977. So it’s been doing this for about 50 years now. 

And they, they take this, there’s a surgical team that removes the pancreas, but there’s actually a second team that is the islet isolation or the islet manufacturing team who is specially trained in this. They actually take the pancreas from the operating room, take it to a special facility that has special equipment and chemicals and essentially process the pancreas. And this is in individualized to each person, the amount of scar tissue and the size of their pancreas. They process this pancreas to get out as many of those islets as we can. 

So rescue back as many of the islets as we can as the concept basically load them up in a medication bag, take them back to the operating room and then where we put them is we, we are surgeons, I don’t do the procedure, I have surgery, colleagues to do that. Our surgeons put an IV into a little vein that comes off the portal vein. So the portal vein is this really vein that brings blood flow into your liver and we just let the islets drip right into that blood flow into the liver and they just go with that blood flow into the liver where there’s a whole bunch of small branches and the islets get kind of stuck or wedged in the liver.

And so that’s the islet auto transplant. It’s a transplant procedure because we’re taking the cells from one place in the body and moving them to the other. But we call it an auto transplant or a tous transplant because that means it’s coming from their own itself. So, as opposed to other forms of transplant, there’s no like medications to prevent rejection because it’s their own body. We’re just moving the cells from one place to another. 

Now, it’s not a perfect process. This isn’t natural or normal for islets to go through this process. So they get beat up and damaged by this process. Everyone in the short term who has this surgery has to go on some insulin therapy while people are recovering from surgery. But about 1 in every 3, individuals overall will come off insulin somewhere between usually about six months to a year after surgery as those islets heal and the other, the other two out of three, most of them will have some functions still of the islets. So they might still need to take some insulin. But the amount of insulin that they need to take may be less and their blood sugars are easier to control than if we didn’t give the islets back. 

And so, so we’re, we’re taking the pancreas out essentially to treat the pain and let people live a normal life, but we’re giving the islets back to make that surgery and the complications of that surgery much easier. And it is a hard process, you know, for patients who go through this, it’s, it’s kind of saved as the last, not quite the last but a late stage procedure because we know that the recovery from the surgery, the diabetes risk, even just the recovery from surgery itself, aside from the diabetes can be a six month to a year process. So we really save this as kind of the one of the last steps in our treatment approaches.

But for those who need this, if we can get in and intervene before they’re too sick at the right time, they can, you know, six months a year after surgery, they can be living a completely different life back to work, back to school, back into normal function. So it can be really life transforming for those individuals who need the surgery.

Shireen: That is just so fascinating to, to know that we could take, we could salvage some piece of the pancreas and then, you know, start transported to the liver and there you have it, it just, it’s just incredibly fascinating, which is from the science perspective, you know, as we’re, and we’re coming to the end of the episode here, I want to quickly touch upon though, how does this surgery work for those with type one diabetes? Are there any differences there or anything that you can highlight for us.

Dr. Melena Bellin: Absolutely. So when people think of eyelet transplants, they might actually think of other forms of diabetes like type one diabetes. We can do islet transplants for type one diabetes. But they are different in the sense that we’re not taking the pancreas out. If someone with type one diabetes has an islet transplant because their diabetes is very, very difficult to control.

We actually leave their own native pancreas in, we get those islets from a deceased donor pancreas. So it’s organ donation. Much like people who have a whole organ pancreas or a kidney or a liver can get an organ from a deceased donor. It’s processed in the same way and it is still put back into the liver. But in that case, because the islets come from a different person, deceased donor, the patients who have that for type one diabetes need to be on anti-rejection medications. 

Those anti-rejection medications carry a lot of risks of their own. And so for that reason, with type one diabetes, the surgery part is actually a lot easier because it’s just the islet transplant, not taking the pancreas out. But the immunosuppression, the anti-rejection medications carry a lot of risk. So it’s really only reserved for individuals who have very brittle or what we call brittle, but very late bile forms of diabetes where they’re having a lot of pretty significant and scary, low blood sugars or high blood sugar episodes that require them to be hospitalized.

Shireen: Interesting with that Dr. Bellin. We are toward the end of the episode at this point. Can you tell us, how can our listeners connect with you and learn more about your work and just nerd out more about islet transplantation?

Dr. Melena Bellin: Absolutely. So I I’m a little bit old fashioned. I’m probably easiest to reach just by email. So anyone is welcome to email me. That’s B as in boy, Ell 0130 at un dot edu, like University of Minnesota dot edu. And, and you mentioned, I work with the National Pancreas Foundation. I highly endorse them as a they’re a nonprofit that just serve and advocate for patients. So I highly endorse them as a patient resource for those with pancreatitis who are looking to learn more fine care centers.

Shireen: Perfect. And with that, Dr. Bellin, thank you so very much for your time. We’ll link up everything in the show notes and how people can contact you. Thank you again for your time and to our listeners. Thank you for listening in on another episode of our Yumlish podcast. You know, it is a time where we head over to social media to continue the conversation. 

Head over to social media, find this podcast post, comment below to tell us how have you or someone, you know, adapted lifestyle changes to address the unique challenges, unique challenges, excuse me, posted by a chronic illness. It doesn’t necessarily have to be chronic pancreatitis, but just generally tell us how have you or someone, you know, adapted lifestyle changes to address any unique challenges posted by a chronic condition.

We will continue the conversation there after the episode to find us again on Facebook, on our Instagram. and we will continue the conversation. Thank you again, Dr. Bellin.

Dr. Melena Bellin: Thank you for having me.

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