Dr. Fumihiko Urano, MD, PhD, Professor of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research at Washington University School of Medicine, talks about a nationwide trial to find treatments for unusual forms of diabetes.
We’ve all heard of diabetes Type 1, Type 2 but there might be a whole spectrum of diabetes.
URANO: That’s correct. So, there are two major types of diabetes. Type 1 diabetes and Type 2 diabetes. And as you know patients with Type 1 diabetes are relatively young. Many of them are children. And they require insulin injections for the treatment. And patients with Type 2 diabetes usually they are older. They tend to be obese. And they take oral medications. And later on, they may need insulin injections. What’s interesting is a growing number of patients do not fall into these two major categories. And we have realized this. And probably maybe 10% of patients who are coming to our clinic have atypical diabetes. We call them patients with atypical diabetes.
So, what makes them atypical? I mean it’s all part of a glucose problem, right?
URANO: That’s correct. So, for example people who come to adult diabetes clinic they have – they tend to be obese, or they have you know some lipid problems. But the patients with atypical diabetes, they are lean. So, they are not obese. And they produce relatively higher amount of insulin from their own pancreas. And also, they have a very strong family history of diabetes. There are so many patients with diabetes in these patients’ families.
What it sounds like to me a little bit is that your kind of describing a lot of people who are diagnosed like pre-diabetic.
URANO: That’s a great question. So, patients with pre-diabetes they don’t necessarily develop diabetes later in their lives. What’s interesting is one-third of obese patients, only 30% of obese people develop diabetes. And we don’t know exactly why you know 33 patients become diabetic later in their lives and 67% of people do not become diabetic. Actually, 33% become diabetic later in their lives and 67% of people will not develop diabetes later in their lives. And we don’t know why. So that’s a really interesting finding.
Do you think right now just doctors are putting patients if they have these signs and symptoms that you know are classified as diabetic just in one category or the other and they don’t have enough options?
URANO: That’s correct. So, there are actually multiple medications for diabetes. But we don’t know. For each patient we use slightly different combinations of medications. There is no clear guideline for choosing proper medication or medication for each patient. And it really depends on the experience of each physician. However, if we understand diabetes better if we understand why you know prediabetes patients become diabetic, why lean people become diabetic or why some obese people do not become diabetic, then we may be able to understand diabetes better. Then we may be able to design personalized treatment for each patient with diabetes.
You know it kind of sounds like to me we do a lot of medical stories like you said. And like diabetes might end up on a spectrum like autism. Like you know there might be like 10 different levels. Do you see that happening?
URANO: Yes, I think that’s happening. That’s a great point. The reason is patients with Type 1 diabetes they are completely insulin dependent. But patients with Type 2 diabetes they don’t need insulin usually initially. But there are many patients fall into in between these two categories. And diabetes is definitely a spectrum of disorder. Then you know maybe if a patient falls into this category maybe we should treat this patient with a combination of two medications. If patient falls into this category, we may be able to choose you know maybe three different medications to better treat this patient. So that’s a very good point. I think diabetes is a spectrum of disorder.
I talked to one doctor, and he thinks that even a form of Alzheimer’s might be Type 3 diabetes.
URANO: That’s right.
Because that’s all glucose in your brain.
URANO: That’s right. Yes, that’s right. So definitely glucose metabolism or abnormal metabolism of glucose is associated in many different types of disorders.
What is the RADIANT trial?
URANO: Yes, RADIANT trial. So RADIANT stands for Rare and Atypical Diabetes Network. So, we will try to identify patients with atypical form of diabetes. Then we would try to characterize them in depth. Then we would try to identify genetic factors associated with the diabetes in these patients. We do a DNA sequence of these patients.
And so, can anyone apply for this trial? Only people with Wash U or?
URANO: So, this is a nationwide study. Anyone who thinks he or she has you know – who thinks has atypical form of diabetes can participate in this trial. So, there is a website for RADIANT Rare and Atypical Diabetes Network. They can go to that website. Then they can type in your – type in their names. Then they can provide us with their information about their diabetes. Then we will screen them. Then we may move them into you know the second stage, third stage or next stage.
How do they know they have an atypical or rare diabetes?
URANO: If you are a patient with diabetes and if you are an adult, if you are lean and if you don’t need a lot of insulin, and also if you have a strong family history of diabetes, you are most likely eligible for the study. And if you are a child with diabetes, you may not need insulin because many patients with Type 1 diabetes need insulin. But if you are a child with diabetes but if you don’t need insulin, you may be able to participate in the study. So, we will look at their medical records very carefully. And we will do some additional blood test. Then we will decide if we are going to enroll them into the study. And if we will do more you know more action – maybe studies on these patients.
I thought it was really interesting in the press release that I read was that your finding maybe these more rare diabetes in minorities. Why do you think that is?
URANO: Yes. So that’s also a good point. In many clinical studies, in many diabetes clinical studies we don’t see many patients from minority groups but in minority groups we may find more atypical forms of diabetes. We know less about diabetes in minority populations. The reason is many minority people have not participated in clinical studies before. So, we are doing our best to recruit minority patients to our study.
It might not really be an increase in minority diabetes just the fact that they’re taking part more now.
URANO: That’s right. We tend to see more Caucasian participants in the study. And we still see more Caucasian participants in our current study. But we are trying our best to recruit more minority patients right now.
Can you tell me a little bit about one of these rare and atypical diabetes ends with Wolfram syndrome?
URANO: Wolfram syndrome is one of the good examples of rare and atypical form of diabetes. Wolfram syndrome is characterized by early onset diabetes. So, patients with Wolfram syndrome develop diabetes around age 6. But then they develop other symptoms later. Around age 10 to 11, they develop so-called optic nerve atrophy. So optic nerve connects our eyes and brain. And in patients with Wolfram syndrome optic nerve becomes thinner and thinner and eventually they become blind, vision loss. And they also develop neurodegeneration. In addition to diabetes, vision loss, they develop neurodegeneration. So, they have brain dysfunction. They develop later in their lives, balance problems. They cannot walk straight. And they have swallowing problems. They cannot swallow food or drink very well. That could potentially lead to aspiration pneumonia. And they cannot control their breathing and that is life threatening. So, Wolfram syndrome is a rare and atypical form of diabetes.
Are these rare and atypical diabetes, are they all genetic?
URANO: That’s a great question. In many cases, not all the cases but it seems like most cases are caused by a change in a single gene. A single gene change can lead to rare and atypical form of diabetes – sometimes a combination of two different genes or three different genes. But as far as I know in most cases a single gene change can lead to rare and atypical form of diabetes.
How many rare and atypical forms of diabetes are there?
URANO: So as of today, there are probably 30 to 40 different genetic forms of diabetes, 30 to 40. Our number is growing.
OK And so, we’re going to go meet Stephanie Snow and her daughter Raquel. Can you tell me a little bit about Raquel?
URANO: Yes. Raquel is a 15-year-old girl. She is very smart. And she is so sweet. And so, she developed diabetes around age 6 just like any other patients with Wolfram syndrome. However, when she developed diabetes, she was diagnosed as Type 1 diabetes because she was young and she was lean. And she needed insulin. So, she was diagnosed as Type 1 diabetes. However later on she had vision issues. She could not see the white board or black board at the school very well. So, then she went to an eye doctor. And the eye doctor looked at her eyes very carefully. Dr. Tychsen found something very strange in her eyes, optic nerve atrophy, which is very, very rare in children. Retinopathy is very common in patients with diabetes, but optic nerve atrophy is extremely rare. Dr. Tychsen happened to be involved in Wolfram syndrome research established by late Dr. Alan Permutt. So, Dr. Tychsen and also Dr. White I think at that time diagnosed her Wolfram syndrome. She went through genetic testing. And then they identified mutations in the Wolfram gene in Raquel. That’s how Raquel was diagnosed with Wolfram syndrome. And her symptoms have progressed in the past several years. But Raquel is a very positive person. So, she participated in all the clinical studies related to Wolfram syndrome in the past nine years, she participated in registry. She participated in research clinic. And she also participated in clinical trials too.
Is there anything to help stop this disease in her?
URANO: So that is a great question. That’s what we are trying to do. So based on the research findings you know we have identified few medications that could be beneficial and that could either stop the progression of Wolfram syndrome. We did one trial which was not a big success. But now we identified even better drug. We plan to start a trial probably next year with a new medication together with a biotech company. Also, we are developing gene therapy for Wolfram syndrome. So hopefully we can bring this type of therapy in the next five to seven years.
And is this RADIANT trial just part of that? That you can collect all this information and all this data to be able to create drugs and medications to stop it?
URANO: So RADIANT study is actually to identify new genes associated with atypical form of diabetes. Our goal is to replicate our partial success of Wolfram syndrome through RADIANT study because Wolfram syndrome research study has developed relatively successfully and quickly because we identified a causative gene for Wolfram syndrome 22 years ago. So, 23 years ago, the late Dr. Alan Permutt identified a gene for Wolfram syndrome which helped many researchers to develop new medications for the disease. So, through RADIANT study we hope to find more genes associated with atypical forms of diabetes. Then based on the functions of these genes we plan to develop new treatments for diabetes.
I’m going to talk to them also about the Snow Foundation. How important is it for you and what you do to have families like that that you know kind of pick up the ball and run with it to save their children but how much do they help you get what you need?
URANO: So patient organizations are very important to develop new treatments for rare diseases. Snow Foundation was developed around 2012. And initially they helped my research financially. Then they expanded their mission. So, what they have been doing recently is to connect patients all over the United States or even all over the world. The reason is rare disease patients feel isolated. And also, in many cases it takes time to get their correct accurate diagnosis. Before the discovery of Wolfram gene, it took several years for each patient to be diagnosed with Wolfram syndrome. It took seven to eight years for these patients to get an accurate diagnosis. Because of the discovery of the gene, it got a little shorter. But because many doctors did not know about the disease, it still took long to get the correct diagnosis for them. But patient organizations such as Snow Foundation can raise awareness of the disease so that you know patients can get diagnosis earlier. Also, they connect patients so they don’t feel isolated because many patients and also patients’ parents feel extremely stressed because it could be life threatening. And they don’t have any information. Snow Foundation has been playing a major role in raising awareness of Wolfram syndrome. And Stephanie Snow Gebel, she is such a wonderful person. You’re going to enjoy talking to her.
Perfect.
URANO: She has you know strong relationship; her dad was a very famous American football player Jack Snow. As you may know Jack Snow played for Rams for a long time. And her elder brother JT Snow played for San Francisco Giants for 15 years. And so, he actually took us to San Francisco Giants game, and we went to the stadium. And we had a chance to talk about Wolfram syndrome which helped us raise funds for the research.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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