Dr. Kevan Herold is Professor of Immunobiology and Medicine at Yale University. The focus of his investigative work is on developing new ways to prevent and treat Type 1 diabetes. He has studied and is developing novel immunologic and metabolic approaches that have been able to prevent the progression of Type 1 diabetes and is involved in a number of national and international clinical studies of new treatments. He is the Director of the TrialNet Center and Autoimmunity Center of Excellence at Yale. He initially reported on the use of an anti-CD3 monoclonal antibody to treat patients with new onset Type 1 diabetes that is now in development for treatment of patients with Type 1 diabetes. His clinical interests are in management of diabetes and complications of diabetes, as well as other Endocrine diseases. Catherine Price interviewed Dr. Herold for A Sweet Life.
What’s the story of your own diagnosis?
It was 1974. I had recently gone to college and got sick pretty quickly after I’d arrived. I think I lost about 15 pounds and was urinating quite a bit — it was classic stuff. I made it to the student health center and almost passed out on the bench waiting to be seen. I wasn’t quite unconscious but I was very ill, in diabetic ketoacidosis. My blood sugar was somewhere in the 600s.
How did you decide to study Endocrinology?
I was in a special program at Penn State to begin with, an accelerated program to go to medical school, even before I was diagnosed. My original interest was not necessarily in endocrinology, but after I was diagnosed, that very quickly changed. My focus on immunology actually came later – but right from the beginning I knew I was very dedicated to working in Type 1 diabetes.
Some of your best known work involves using a drug called an anti-CD3 monoclonal antibody to modify the progression of Type 1 diabetes in newly diagnosed patients — a drug that is currently in Phase 3 trials, working toward FDA approval. What are some other of your favorite research projects that you’ve been involved in?
In addition to the anti-CD3 work – determining how it works and in whom it will work, I think the studies we’ve done in mice to try to look at the natural progression of beta cell loss and beta cell recovery after immune therapy have been particularly exciting. We have some very interesting work that is going on now to look at beta cell death and ways of protecting beta cells from immune attack.
What are you working on currently?
Well, obviously the clinical trials to treat and prevent diabetes — I spend a lot of time doing that, which is particularly rewarding because it’s an opportunity to bring basic science to the treatment of patients. Some of the other work is figuring out if we can identify the immune cells that actually cause beta cell destruction in people and determine how best we might be able to stop them from killing islets – and then figure out ways to make islets regenerate.
What’s the latest news on anti-CD3?
The prevention trial is very close to getting started. [Herold plans to give the drug to people who are at high risk of developing Type 1 diabetes, to see if giving the drug preemptively might prevent the development of the disease.] I’ve always said that will be the most exciting trial I’ve ever done — if you could actually stop diabetes from even appearing, that would be terrific.
What about the possible development of a treatment derived from stem cells? Are you excited about that as well?
I’m cautiously optimistic about it. It could turn out to be very exciting. The technologies are changing very rapidly so I am really anticipating applications to treatment may become a reality sometime soon.
How has the field changed since you first got started? Are you more optimistic now than you’ve been at other times in your career?
Oh, yes. I’m fairly optimistic that over the next couple years there’ll be some drugs approved that will actually change the natural history of the disease. That will be the first time that’s ever happened, and it will be very exciting – we’d be able to treat the actual fundamental process that causes diabetes as opposed to just providing replacement insulin. That would change the picture of the disease entirely.
What do you think it will take to cure Type 1 diabetes?
I think it’s probably going to take a few things. One thing, for sure, is a means of stopping the autoimmune attack. However, in addition, I think it will require more – either replacement of the lost beta cell mass or even a way to stimulate production of insulin by the existing beta cells. It would be nice if there was a means to stimulate beta cell regeneration and recovery but the evidence that that can be achieved in man is still not clear. Nonetheless, there are physiologic conditions, like pregnancy, in which this seems to occur so I am still optimistic that progress can be made in this area.
How do you manage your own diabetes?
With a lot of attention! People with diabetes spend a lot of time managing it. I do, too, like everybody else with diabetes. It’s every day, and it’s every hour of every day.
How do you cope with it emotionally?
I, like everyone else with diabetes, can find it tiring to never get a break from it, and to feel like if something goes wrong, that I am the one to blame. Sometimes I feel as though I could do a whole lot better and I feel like I let myself down, but I try very hard not to let it stop me and I try not to let it get in my way of doing what I want to do and accomplish. I just stick at it. It would be easy to let it get the upper hand over your life – that’s why I get comfort in maintaining control – I stay on top if it rather than the other way around.
How do you manage your diet?
People who know me would say that my diet is very rigorous, and it’s true. I am very careful about food selections. I eat at certain times, and I’m very careful about what I do eat. There’s no “just eat whatever you feel like” in my diet. Everything is pretty thought out. If I don’t know what something is, I don’t eat it.
What do you mean?
If there’s a nutritional label or if I know exactly what it is, I’ll eat it. But otherwise, I really stay away from unknowns. The interesting thing is that there isn’t a whole lot of food that I don’t eat for that reason – because most of the things I want to eat, I have a pretty good idea about their nutritional content.
How did you learn that?
I read a lot of food labels. I used to weigh my food and I still use measuring cups when I can. By now, though, most of it is from experience.
In your clinical practice, what’s one thing you wish you could change in how your patients manage their diabetes?
If I could change one thing about what most of my patients do it would be diet. It’s a huge thing that I think most people don’t pay enough attention to. We spend a lot of time going over insulin regimens, but at least in my own diabetes, the diet is the greatest variable – when things don’t go well either with low or high blood sugars, the problem is generally food and not insulin.
What are some misperceptions you think the American public has about diabetes?
I think that many people have a poor understanding of diabetes – what it’s about, what causes high or low blood sugars and what they should do about them. In addition, most people don’t really have an appreciation of what it is like to live with the disease – particularly Type 1 diabetes. People tend to focus on aspects that I would consider of minor importance – like, for example, injections. Well, injections really are trivial. The more significant aspect of the disease is its need for constant attention – every day and all day.
What do you think is the hardest part about living with diabetes?
I would say it’s the curb on spontaneity and the attention it demands. The insulin pump has helped that a great deal – not just because insulin can be administered easily and in very precise amounts but also because since it can be precisely adjusted, the swings in blood sugar are modulated. I remember that with older formulations of insulin and ways of administering it, you felt that things were always changing. A colleague of mine who also has diabetes once joked that when there was a cure that he was just going to sit in Central Park and do nothing – just sit there. In other words he would welcome the day when his blood sugar was perfectly stable and he didn’t have to think about what was going to happen in the next hour or later in the day.
What suggestions or advice do you have for someone who has a family history of Type 1 diabetes but hasn’t yet been diagnosed?
For someone with a family history of Type 1 – a first or even second degree relative — I would suggest getting screened at this point for signs of autoimmununity – autoantibodies against antigens that are associated with Type 1 diabetes. These serologic markers can identify those at risk for developing the disease. If you’re under the age of 18 and, in addition to having autoantibodies, have an abnormality in glucose tolerance, your chance of developing Type 1 diabetes is very high over six years. And if you’re over 18 it is also very significant. But if the tests come back positive, there are now some new prevention trials that may be helpful in preventing the development of the disease. There are a whole lot of sites around the country that are doing screening for Type 1 — most of the academic centers are involved, as are many physicians.
What advice do you have for people – or parents of children – who have been recently diagnosed?
Get involved in a clinical trial. There are a lot of trials going on right now for people with recently diagnosed diabetes and there are going to be a whole lot more very shortly. Timing makes a difference because when you’re first diagnosed, you usually have some functioning beta cells, and a trial might be able to help you preserve some of their ability to produce insulin.
In fact, from the researchers’ perspective, we need just about every single newly diagnosed person out there to get involved in one of these trials. It’s difficult to say which one is better than the other, but one thing is true; if most people don’t get involved, then we’re never going to move forward. It almost doesn’t matter which one you’re involved in. Just get involved – so that things aren’t the same in five years.
Where can people find clinical trials?
There are several great resources, like:
The Juvenile Diabetes Research Foundation
The National Institutes of Health,
What gives you hope?
First, that thanks to all the progress that’s been made, the prognosis of people with diabetes is completely different than it was when I was diagnosed. When I was diagnosed, people pretty much accepted that having diabetes meant a shorter life span and a very high risk of developing complications like blindness or losing a limb. That dismal prognosis has improved greatly – it’s not at all the same. The fact that the work that many of us have been doing over the past decades is developing into some sort of real benefits for patients is very encouraging. It certainly keeps me going.
Do you think type 1 has had any positive effects on your own life?
Yeah, it has, in its peculiar way. I think that the discipline it makes you develop is valuable, professionally. And, of course, Type 1 diabetes certainly has given me something to work toward.
Catherine Price is a regular contributor to ASweetLife, she writes the blog The Reluctant Diabetic
Are you doing or do you know of anyone investigating use of your cd3 or stem cell research on type 2 diabetes and/or rheumatic arthritis, both of which I have.
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