NASHVILLE, Tenn. (Ivanhoe Newswire) - Kidney failure, blindness, amputation, heart attack and stroke. They're some of the serious effects people with type-one diabetes could face. Now doctors are studying ways to cure the disease before it happens and even get rid of the disease in people who already have it.
It can be a pain, but it's a necessity for millions. Checking your insulin level every day is something Kerby Bennet is trying to avoid. A few years ago her twin sister, Taylor, was diagnosed with type-one diabetes.
"It was a shock to us, especially because she was 17 when she was diagnosed," Kerby said.
Because her identical twin has it, Kerby has a 65 percent chance of developing the disease too
"It's nerve wracking," Kerby said.
Now, she's the first person to enroll in a clinical trial at Vanderbilt University testing the drug Teplizumab.
"It's been well studied in individuals who have been newly diagnosed with diabetes," Dr. William Russell, director of pediatric endocrinology and diabetes at Vanderbilt University said. "What if we take someone who is at high risk to develop diabetes, can we actually prevent it?"
The drug battles an immune system protein called CD3. The goal is to find out if it can also stop the destruction of the insulin-producing cells in the pancreas before diabetes occurs. Meanwhile researchers at the University of Colorado are curing it in animals. By isolating the specific t-cells that attack the pancreas, they developed a drug that can stop diabetes from developing and even reverse it in mice that already have it.
Kerby hopes the drugs will help prevent her from developing diabetes and someday cure her twin sister.
"I think research like this makes it possible," Kerby said.
Researchers will follow Kerby for up to four years. Doctors said their ultimate goal for the trial is to enroll 150 people in the U.S. and at a few foreign sites. For more information on how to enroll go to www.diabetestrialnet.org.
BACKGROUND: Diabetes is a group of diseases marked by high levels of blood glucose resulting from flaws in insulin production, insulin action, or both. It can lead to serious complications and premature death, but steps can be taken to control the disease and lower the risk of complications. (Source: Center for Disease Control and Prevention)
TYPE 1: Type 1 diabetes develops when the body's immune system destroys beta cells in the pancreas, the only cells in the body that make the hormone insulin that regulates blood glucose. It most often strikes children and young adults, though disease onset can occur at any age. In adults, type 1 diabetes accounts for approximately 5 percent of all diagnosed cases of diabetes. Risk factors may be autoimmune, genetic, or environmental. There is no known way to prevent type 1 diabetes. Several clinical trials for preventing type 1 diabetes are currently in progress or are being planned.
GENES VS. ENVIROMENT: With the growing worldwide epidemic of diabetes, a key question is to what extent is diabetes in our genes and to what extent is it due to changes in our environment? About 40 percent of people in the U.S. carry one or more of risky genes, but only about one out of 100 in this category will actually develop the disease. This reflects the fact that there are likely one or more environmental factors that trigger diabetes in these genetically susceptible individuals. What exactly these environmental factors are remains unknown.
"It's a little hard to say that sixty five percent is genes and thirty five percent is environment. If people live to be 150, that sixty five percent number might turn into eighty five percent or ninety percent," Dr. William Russell, from Vanderbilt University told Ivanhoe. "The genes set the stage for that but there are probably environmental triggers that actually initiate the process."
STOPPING IT: Teplizumab has been created to change the function of the T lymphocytes that mediate the destruction of the insulin-producing beta cells of the islets of the pancreas. Teplizumab binds to an epitope of the CD3-epsilon chain expressed on mature T cells and by doing so, may modulate the immunologic response that is a key component of the disease. If Teplizumab is effective and has the ability to preserve or protect beta cells of the pancreas, patients may require less injected insulin and their blood glucose levels may be easier to control. Teplizumab represents a key shift in the management of autoimmune disease that focuses on the introduction of tolerance rather than broad spectrum immunosuppression.
Type 1 Diabetes TrialNet is an international network of researchers who are exploring ways to prevent, delay and reverse the progression of type 1 diabetes. TrialNet is conducting clinical trials with researchers from 18 Clinical Centers in the United States, Canada, Finland, United Kingdom, Italy, Germany, Australia and New Zealand. Studies are available for people newly diagnosed with type 1 diabetes, as well as for relatives of people with type 1 diabetes who are at greater risk of developing the disease.
Dr. William Russell, Director of Pediatric Endocrinology and Diabetes at Vanderbilt University, talks about beating diabetes before it develops.
Can you explain the difference between Type I and Type II diabetes?
Dr. Russell: Type I diabetes has very different origins than Type II. Both are characterized by elevated levels of glucose in the blood, which can result in damage to body organs. Type I diabetes used to be called juvenile onset diabetes because it develops predominately in children and young adults. It is diagnosed as young as six months of age and its peak incidence is in teenage years, but it can be diagnosed well into the fifth and even sixth decades of life. The major difference between Type I and Type II diabetes is that Type I diabetes is an immune system disease. It starts when the patient's immune system, which ordinarily would not bother their insulin producing cells, decides that they are foreign and begins to destroy them. Type I diabetes is an "autoimmune" disease and is related to other autoimmune diseases such as hypothyroidism, celiac disease, and rheumatoid arthritis. Over time, there is a loss of the pancreatic beta cells, which produce insulin. Insulin controls the entry of glucose into cells, and as a consequence of inadequate insulin production, glucose levels increase in the blood. In Type II diabetes the body continues to produce insulin, but in contrast to Type I, the cells have difficulty in responding properly to insulin, resulting in the same high levels of glucose in the blood and later organ damage. Type II diabetes used to be called adult-onset diabetes, but we're diagnosing it in younger and younger people, including children, because its onset is accelerated by obesity and lack of physical activity.
Our ability to predict someone's risk of developing Type I diabetes has become very sophisticated. While there are certain genes known to be involved in causing both types of diabetes, there are so many genes implicated that there is no simple genetic test to predict diabetes risk. However, since Type I diabetes is primarily immune system disease, we can detect the presence of antibodies in the bloodstream of individuals who are undergoing this autoimmune assault on their pancreatic beta cells many months or years before they actually develop Type I diabetes. This gives us a golden opportunity to try to stop the destruction of beta cells before diabetes develops.
Tell me about the trial.
Dr. Russell: We're part of a network of 18 centers around the world called Type 1 Diabetes TrialNet. TrialNet is funded by the National Institutes of Health and its goal is to develop ways to prevent or delay the development of Type I diabetes. To identify the people who are at highest risk to develop Type I diabetes we start by screening family members in a study called The Pathway to Prevention. Having a close blood relative with Type I diabetes increases one's risk substantially. With an identical twin with the disease, your risk is about 2 in 3 to develop it during your lifetime. If your brother, your sister, or your mother has type 1 diabetes, your risk of developing the disease is about 1 in 20. However, if your father has the disease, your risk could be as high as one in ten. In contrast, without a family history of Type I diabetes, the risk is somewhere around one in two hundred and fifty.
The ambitious goal of TrialNet is to screen two hundred thousand people and this past summer we screened our hundred thousandth subject. When diabetes antibodies are detected in the blood, we have an indication that the immune system is starting to damage the beta cells. There's further testing that we can do to refine that risk. We test certain genes, we test how the person at risk can respond to glucose by performing an oral glucose tolerance test and we look at a test called hemoglobin A1c to determine what the subject's blood glucose has been averaging in the preceding several months. As a result of this testing we can come up with fairly good predictive numbers to say that a person's risk is low, moderate, or high.
In the particular study that Kerby is participating in, we are testing a drug, Teplizumab, that has been shown to preserve the beta cells in a person who is newly-diagnosed with diabetes. At diagnosis, a significant number of the beta cells remain, and the patient still has the ability to produce some insulin. Teplizumab has been shown to slow the decline in that last twenty or thirty percent of insulin-producing capacity in people newly-diagnosed with diabetes. The rationale for the current study is to start the treatment earlier. If we have somebody who is at high risk to develop diabetes, can we actually prevent it and not wait until they have the disease to do something? Our goal with subjects like Kerby is to prevent them from developing Type I.
How does the testing process work?
Dr. Russell: Family members of someone with Type I diabetes are screened. If they have positive antibody tests, they have a glucose tolerance test. They drink glucose and we measure how their blood levels of glucose respond. That's typically how we diagnose diabetes. To qualify to be in this particular study of Teplizumab, individuals must have what we call dysglycemia. It means that blood glucose levels are not normal, but not yet in the diabetic range. We know from past studies that people who have dysglycemia and antibodies in their blood have somewhere around an eighty five percent chance to develop Type I diabetes in the next five years.
Can you talk about Kerby?
Dr. Russell: Kerby has several risk factors that put her at very high risk to develop Type I diabetes. She has an identical twin with Type I diabetes. We know that puts her at least about a sixty five percent risk over the course of her lifetime to develop the disease. That's just from the statistical analysis of identical twins. Kerby entered the TrialNet program, had the screening test and we found that she was already showing signs of having mounted an immune attack on her beta cells. She came back for further testing and was found to have dysglycemia. It's not just that antibodies are present, but there's clear indication from her glucose tolerance testing that her beta cells have been extensively damaged. The glucose levels are not diabetic yet and they're not perfectly normal, so she fits this label of dysglycemia that we talked about. That puts Kerby in the risk category of about eighty five percent to develop Type I diabetes in the next five years and we want to stop that.
Did she receive the drug or a placebo?
Dr. Russell: We don't know. Since we don't know yet if this drug works, the standard way to assess the effectiveness of a new therapy is to do what's called "double masking" of all involved. Kerby doesn't know what's she's getting and we don't know, either. Ultimately, when the study is completed, all will be revealed. We make it very clear to subjects like Kerby that we cannot guarantee that they are getting the actual study drug. She had a series of daily infusions of the drug or placebo over a two week period back in July and that is complete. There were blood tests every day while she was getting the drug to check on the function of her immune system and to make sure that we were not causing any harm. Now she's in the phase where we're periodically reassessing her ability to make insulin on her own and maintain good glucose levels. So far, so good with Kerby.
It's probably too early to tell if anything has changed in her case right?
Dr. Russell: Yes it is too early to tell. This kind of a study isn't complete until we have studied enough of subjects to make statistical comparisons and they go through it for the full period of observation.
How long until do you think until we can have some kind of answer?
Dr. Russell: It's going to be four to six years at least. We have to accrue an adequate number of individuals at the various sites around the country that are participating in this. Vanderbilt is one of seven sites that are testing this drug. We're talking a number of years and none of us will have the details revealed to us until we're at that point. We're all very eager to see that kind of information.
Do you think in ten years we could be staring at something that could revolutionize the way we treat or the way we see Type I diabetes?
Dr. Russell: This work has tremendous implications. If we are able to prevent Type I diabetes, that means we're able to modulate the immune system to slow down or stop the attack on beta cells. There is a separate line of research going on in ways to stimulate healthy beta cells to regrow, to regenerate themselves. If we can turn down the immune system to the extent that that the beta cells will not to be destroyed any more and then stimulate the remaining healthy beta cells to regenerate themselves, then we are starting to look at the possibility of reversing somebody who already has diabetes into a pre-diabetic or maybe even totally non-diabetic state.
Kerby's sister was diagnosed at seventeen, what were the odds that she was diagnosed with diabetes but Kerby has not?
Dr. Russell: Identical twins share all the same genes. There's not just one gene that predisposes someone to develop Type I diabetes. There are multiple genes involved and we really don't have a good handle on all of the genes that contribute to this process. If one identical twin develops the disease, the other has a roughly 65% chance of developing it as well, which makes it very clear that genes aren't the whole story. There's very good evidence that the genes set the stage for developing the autoimmune process, but that environmental factors actually trigger the process. It's very possible that two people will share the same predisposition but will differ in terms of when or if they're exposed to the triggers that actually turn on the autoimmune process that ultimately leads to the diabetes.
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