"Weighing" in on a diabetes discovery

BACKGROUND:  Type 1 diabetes, affecting 5% of people with diabetes, is usually diagnosed in young adults and children.  It was previously known as juvenile diabetes.  In type 1 diabetes, the body does not produce enough insulin.  Insulin is a hormone needed to transform starches, sugar, and other food into energy.  In most cases of type 1 diabetes, people need to inherit risk factors from both parents.  However, genes alone are not enough to trigger the disease.  For example, identical twins have identical genes.  One twin can have type 1 diabetes and the other has only a 50% chance of inheriting it also.  Researchers believe that a predisposition to the disease can be inherited then something in that person's environment triggers it.  They think one trigger might be related to cold weather because type 1 diabetes develops more often in winter than summer and is more common in colder climates.  It is less common in people who were breastfed.  (Source: www.diabetes.org


YOUR CHILD'S RISK:  Generally, if a man has type 1 diabetes, the odds of his child obtaining diabetes is one in 17.  If a woman has type 1 diabetes and their child was born before they were 25, then her child's risk is one in 25; if the child was born after they turned 25, the child's risk is one in 100. If the parent developed diabetes before age 11, then the child's risk doubles.  If both of the child's parents have type 1 diabetes, the risk is between one in 10 and one in four.  However, there is an exception to these numbers.  Close to one in every seven people with type 1 diabetes has a condition called type 2 polyglandular autoimmune syndrome.  These people have thyroid disease, poorly working adrenal glands, and also have type 1 diabetes; some even have immune system disorders.  If a parent has this syndrome, then their child's risk of getting the syndrome on top of type 1 diabetes is one in two.  Researchers are learning how to predict a person's odds of getting diabetes. (Source:  www.diabetes.org)


NEW TECHNOLOGY:  Type 1 diabetes happens when the body attacks its own beta cells, which are found in the pancreas.  Beta cells produce insulin.  The study at the University of Florida has linked people with type 1 diabetes to having smaller pancreases.  If there is a smaller pancreas in type 1 diabetes patients, then the number of insulin-producing beta cells is lowered too.  During the study, researchers weighed 164 organ donors' pancreases.  Results showed that people who had been diagnosed with type 1 diabetes or who were at risk for the disease had smaller than average-sized pancreases.  A normal pancreas weighs 80 grams.  A pancreas of people with type 1 diabetes weighed half that size.  People at risk for the disease had a pancreas weight of approximately 60 grams.  Researchers say that beta cells grow in utero and can continue to develop until the child is around five years old.  The study's results stress the need to look earlier in people who are at risk for type 1 diabetes.  So the next step in research is to look at younger people and measure the volume of their pancreases through MRI imaging.  (Source: www.news.ufl.edu)


Martha Campbell-Thompson, DVM, PhD, professor of Pathology, Immunology, and Lab Medicine at the University of Florida, talks about new innovative research about the pancreases in people who are at risk for type 1 diabetes.

Can you tell us about the study that you guys did? Is it a first of its kind? 

Dr. Campbell-Thompson: It is a first of its kind made possible by a very unique bio-banking program that is looking at causes of type 1 diabetes. This program is called the JDRF Network for pancreatic organ donors with diabetes or nPOD for short. This program interfaces with the national organ donor network and works to recover pancreases that are donated for research and are not able to be transplanted. The pancreases come to this bio-bank at the University of Florida. Part of the processing of those pancreases is to simply weigh them. We saw that donors at high risk for developing type 1 diabetes had pancreases that weighed less compared to control donors. So, that was the start of this study.

What did you think when you first noticed that there was this pattern of pancreases weighing less than normal? 

Dr. Campbell-Thompson: It was very exciting to us because before this study, there was essentially nothing known about the pancreas weight in people at risk for type 1 diabetes. Thankfully, most people with diabetes do not succumb to the disease. They are diagnosed, but then there is medical treatment that allows them to live with the disease. So, by finding that the pancreas weighs less, this implies that even before someone becomes diabetic, they may have fewer insulin-producing beta cells because insulin probably affects the size of the pancreas in addition to blood glucose levels. This is the first time this aspect has been studied.

How big of a difference is it between a normal pancreas and one that might become diabetic? 

Dr. Campbell-Thompson: The weights of these pancreases were about 25% lower than control pancreases. It has been known for a long time that after someone has type 1 diabetes, and if they happen to die at disease onset, those pancreases can weigh half as much as a normal pancreas. So, it was already known that people with established disease had smaller pancreases, but it was not known that this weight loss could be happening many years before signs of diabetes occur. We are very excited. If this finding can be replicated in a larger number of patients, then it could have implications for what causes type 1 diabetes. The whole picture is by no means clear. We know there is a genetic component. We know that there is an environmental component, like viruses that could be causing type 1 diabetes.  We know also that it can be the individual themselves; someone can be an identical twin and not get diabetes, while their twin gets diabetes. There are so many unanswered questions and this study provides one more piece to the puzzle of what causes type 1 diabetes.

What are you going to do with this information now? 

Dr. Campbell-Thompson: We need to substantiate it in additional patients and are planning to look at this in living patients using people enrolled in clinical trials. They may have a sibling or parent who has type 1 diabetes and they have enrolled in clinical trials to study whether or not they are going to get type 1 diabetes. So, we want to interface with these clinical trials and in addition to the other tests being done, measure their pancreas volume using something simple and safe, like an ultrasound.

Now that you have this information, the hope is that you could stop the onset in the beginning if you could find out why the pancreas is smaller?

Dr. Campbell-Thompson: Exactly. There could be maternal factors that are reducing the size of the pancreas. With this finding, we are starting to consider the possibility that people who eventually develop type 1 diabetes could possibly be born with a smaller pancreas to begin with. Then certain things come along, including their genetic risk, such as exposure to a virus. If they are starting with a smaller pancreas, then when they get these kinds of injuries or stresses; maybe those are the ones that go on and actually get diabetes. On the other hand, someone who is born with a normal pancreas might be able to handle these injuries and will not develop type 1 diabetes. It is also very important for people involved in prevention studies. If we do find this difference, those people who have a smaller pancreas might be treated differently to prevent the onset of type 1 diabetes.

Do you think people are born with smaller pancreas or can it shrink overtime?

Dr. Campbell-Thompson: Absolutely either or both is possible. We do not know at this point, but we now have new avenues to explore. By using an ultrasound, we may be able to screen a lot of patients and see whether or not they eventually develop type 1 diabetes. There are studies involved in environmental determinants of type 1 diabetes so even newborns are screened for having at risk aspects of type 1 diabetes. In some of the clinical trials, they are already getting a lot of the testing done for other aspects of diabetes that we'd want to include in our studies so we would just propose to add measuring their pancreas volume into this picture.

How long would it take to have a more definitive picture of what the role of a smaller pancreas plays?  

Dr. Campbell-Thompson: It is going to take many years because people are so different, just as I mentioned with the identical twins. There are so many factors. Environmental factors are really important too. For instance, Finland has the highest rate of type 1 diabetes in the world and it has been increasing over time. No one understands why, but they are looking into many factors. We do not know yet why one country like Finland or some other places in the world have such a high rate. The issue with type 1 diabetes is that it often happens in children. Once you have type 1 diabetes, from then on, you have to take insulin before a meal and during other times. While it is a disease that can be effectively treated, it is a big burden on the patient and their family. 

So what is the next step? Are you going to continue to weigh pancreases?

Dr. Campbell-Thompson: The nPDO bio-bank is continuing to try to obtain these pancreases from organ donors that are not used for transplants. We are also meeting and working on a strategy to apply for funding to interface with those ongoing clinical trials in people at risk for developing type 1 diabetes. We know that people who develop type 1 diabetes have a smaller pancreas. Now, we just need to turn back the clock, so to speak, and start looking at people who are at risk.  There are a lot of potential enrollees here at the University of Florida. The UF Diabetes Center is very active in monitoring people on clinical trials. Clinical trials can involve hundreds of people and take many years, but it is the first step to unraveling some of the mysteries for such as complicated disease as type 1 diabetes.

How difficult will it be to interface with those ongoing clinical trials?

Dr. Campbell-Thompson: There will be some difficulties and there have been a lot of discussions going on. The first thing is really to see whether or not the pancreas can be well visualized using a simple ultrasound. A lot of people have had ultrasounds. We have some very good pediatric endocrinologists who will be working with these patients and seeing if they can measure the pancreas with an ultrasound. Some of these patients, who are enrolled in other clinical trials, may also be willing to let us do an MRI to see which method is most accurate in children. Many people have had MRIs done and they have to lie very still in order to get a good one. We expect some children will be able to do that, but in other children there would be no way. So, there is difficulty expected and we will be starting a pilot study here at the University of Florida. Then we hope this would be expanded to the sites involved in the NIH clinical trial projects that look at prevention of type 1 diabetes. 






Dr. Martha Campbell-Thompson

Professor of Pathology, Immunology, and Lab Medicine

University of Florida