Transcription:

Melanie Cole, MS: Welcome to UAB Med Cast. I'm Melanie Cole, and joining me today is Dr. Anath Shalev. She's an endocrinologist and a professor at UAB Medicine, and she's here to highlight new frontiers in diabetes research. Dr. Shalev, it's a pleasure to have you join us today. Can you start by telling us a little bit about the UAB Comprehensive Diabetes Center?

Dr. Shalev: Sure. Thank you for having me. So our comprehensive diabetes center, its mission is really to do cutting edge diabetes research and provide insight and breakthroughs that ultimately, will improve the lives of those affected by diabetes and as type one and type two diabetes in our community and beyond. We are a universitywide interdisciplinary research center, or York, as they like to call it here, and have 200 faculty members from all schools on campus and obviously many different departments.

With that, it is truly a multidisciplinary center and serves as a platform, an engine for collaborative research, to avoid potential silos that can be found at some institutions. So it also, by doing so, it spans the full spectrum of very basic translational clinical and outcomes research. And so, it's obviously very important in general, but especially for a complex disease such as diabetes and for a problem that is such a special issue for us here locally in the deep south. And since some still refer to us as the buckle of the diabetes belt that spans across the deep south.

Melanie Cole, MS: Well, it certainly is really an epidemic right now goes along with this epidemic that we've been seeing of obesity and the increased comorbidities that go along with diabetes. Tell us a little bit about what's new in exciting research and advancements that have been made at the UCDC, as I understand it, there's new drugs on the horizon. Tell us about some of the things going on there.

Dr. Shalev: So Sure. Obviously given the complexity of diabetes and the large number of researchers we are working that are working on many different aspects of the disease, I can't cover everything, but so I will try to give you just one example how we try to move discoveries from the bench to the bedside. So roughly two decades ago, we identified a protein called tick snip that is elevated in diabetes and that has detrimental effects on pancreatic eyelets and on the beta cells that obviously produce insulin. We then discovered that the commonly used blood pressure medication. Rapmill can normalize tick snip levels and that rapmill protected mice from diabetes and also was able to reverse over to diabetes in those mouse models.

We then were able to translate these findings into humans with recent onset type one diabetes and found in a randomized placebo controlled trial that once a day oral rapmill enhanced eyelet function. And limited the amount of insulin injections that were required. And with that also reduced the number of hypoglycemic events that patients experienced. Obviously a major issue for people with type one diabetes. And so now what we are excited about is that most recently we found that these beneficial effect are maintained for at least two years after the initial diagnosis of Type one diabetes, as long as individuals continue to take the medication.

And so obviously this opens up new possibilities for physicians to treat their patients with diabetes. Since while RapMill is not FDA approved for diabetes, it has been approved for over 30 years for hypertension and can be given off label, based on the physician's assessment of that patient. And so, this is also part of a translational pipeline that we have started here at the center and trying to move other drugs and other possibilities and new therapies along this way.

And now you also mentioned kind of newer things as well, with finding this as proof of principle that addressing tick snip and its signaling is effective not just only in animal models, but also in humans. We had set out to identify new drugs and new compounds that would do the same thing, but more specifically and have identified a small molecule. That can also inhibit tick snip, and have launched a small company to bring that from again, the bench to the bedside and hopefully into clinical trials.

Melanie Cole, MS: That's fascinating. What an exciting time to be doing research in your field, Dr. Shalav. That's not only innovation in terms of medicational interventions and even new technologies and devices. But you mentioned this just briefly, innovation as a philosophical shift from providers working in silos to working together. Can you speak about how this multidisciplinary approach at the UAB Comprehensive Diabetes Center is really so important for these patients?

Dr. Shalev: Yes, absolutely it is very important and as I mentioned briefly before, it's important in every aspect, but particularly in a disease that is as complex and touches upon so many different aspects, o also of the patient's life and health. And so, no one these days with the advancement of technology and the innovation can be an expert in everything. And so in order to efficiently move things forward and get the best insight we have to work together.

And that's what our center allows us to do. And also to address different aspects of the disease simultaneously. You mentioned complications before. We are lucky to have other centers on campus that address pretty much every other organ system that diabetes affects, such as kidney neuroscience of tology, cardiovascular. And so we are working very closely with our colleagues in those centers to consider these other aspects of the disease when we're trying to find new therapies.

Melanie Cole, MS: What are you most looking forward to this year with the UCDC? Tell us a little bit about what you see happening on the horizon with the study you discussed and others.

Dr. Shalev: Well, so for one, with the improvements in terms of the Covid-19 pandemic, we're slowly returning to in person visits and so with that, we're able to connect better with our colleagues and move those developments further along. We are very much looking forward to implementing more of the rapmill with other groups. There's a large study going on in Europe. I just returned from a meeting in Stockholm where this was discussed. They having a multi site study using rapmill as the basis and then combining it also with other immunosuppressive regimens, to try to find the best combination for diabetes treatment for type one diabetes treatment.

And so we were excited to see what the results from these studies will hold and to see others starting to use some of our findings in their research. We are also obviously looking forward to, move, the small molecule forward with Ticzimat and to get in d approval to be able to start clinical trials with that small molecule. That's another big aspect that we're looking forward to in terms of the drug development. And then finally, from a center perspective, we also were excited since we have just launched a major strategic recruitment initiative and diabetes research in collaboration with the [inaudible] School of Medicine to recruit up to 10 new faculty members.

And so with new growth phase, we are really hoping to, have a major impact and to advance the ongoing research exponentially with getting people in that can network and collaborate with the already existing faculty and really go even another level up.

Melanie Cole, MS: Dr. Shalav you mentioned briefly before bench to bedside. So you're doing all of this exciting research. How do you feel it will impact physician's treatments, primary care provider that are also dealing with these patients and working with these patients in a medical home situation? In some rural areas, there's other community endocrin. How do you see this research impacting their treatment? How do you envision it translating directly to patient care?

Dr. Shalev: That's an excellent question. And in fact, I think the findings with Rapmill are a great example of how really kind of basic research can impact very clinical, primary care. With the traditional treatment of type one Diabetes is often reserved for endocrinologists and is often associated with high end technology of insulin pumps and continuous glucose monitoring systems, etcetera, etcetera. And some of those things may not be available everywhere into everyone. However, if we can optimize treatment and reduce the need for large amounts of exogenous insulin, for example, with an oral medication given just once a like rapmill, we can have a major impact and can open up that ability to help people to primary care physicians.

It's an addition rapmill, as an example, is very, very cheap. So it really opens up opportunities to help communities that otherwise would be limited to very expensive and very complicated treatment options. That they may not have access to. So again, I think it would, really give an opportunity for physicians to enhance the therapy that they offer to their patients.

Melanie Cole, MS: You make a great point. It's pretty easily accessible and you can get it, as you say, very inexpensively. As we wrap up, how would you like the community and community providers to support Diabetes Awareness Month coming up in November? Really tell us what you would like referring physicians to know about the UAB Comprehensive Diabetes Center and when you feel it's so important that they refer?

Dr. Shalev: Yes, that's a great question. I mean, the best way to help us is to get involved and spread the word that we have a center such as ours, you know, in our backyard here, to, let people know that there are people working pretty much nonstop to try to find better therapies and better treatment options for them. So they feel that we're really there to help. People can sign up for our newsletter, get information, and also share their stories where we're open to. We really want to have the, a dialogue with, providers as well as with patients. So one way to do this is through website. And so that's uab.edu/diabetes. And we can be happy to connect and to make connections with whoever is interested.

Melanie Cole, MS: Thank you so much, Dr. Shalav for joining us today. And a physician can refer a patient to the UAB Comprehensive Diabetes Center by calling the MIST line at 1-800-UAB-MIST, or by visiting our website at uabmedicine.org/physician. That concludes this episode of UAB Med Cast. For updates on the latest medical advancements, breakthroughs in research, follow us on your social channels. I'm Melanie Cole.