David Klonoff: 0:13

Hello, welcome to Diabetes Technology Report. I'm David Klonoff, I'm at Sutter Health and we have a very special guest today Health and we have a very special guest today. I'm going to introduce my co-host, dr David Kerr, and he will introduce her and start the interview.

David Kerr: 0:30

David, Thanks very much, david, and welcome to everyone. I'm David Kerr. As usual, I'm speaking to you from Santa Barbara, california, and it's great we have Leanna Billings on today, who is an authority, an expert, on certain aspects of diabetes. So come to that. So, leanna, welcome, it's fantastic to have you on board today. One of the things we like to ask to set the scene really is how did you end up being interested in diabetes? Our audience is very curious about that.

Liana Billings: 1:03

Yeah, well, it's been an evolution, Fortunately, when I was in undergrad I had the experience in working in an epidemiology lab at University of Illinois in Chicago and we were interested in looking at some of the social and economic factors that impacted type 1 diabetes control in kids in Chicago.

Liana Billings: 1:28

It was very eye-opening to me.

Liana Billings: 1:31

At that point I was a lowly lab member and I did a lot of data collection that were based off of interviews with families, but I was really able to kind of see right into the homes and into the life of people living with type 1 diabetes and realizing, you know really, the significant challenges that they face every day in trying to control blood sugar but also trying to deal with getting medical supplies and medical care and other things related to the condition.

Liana Billings: 2:00

So that piqued my interest and then I went on to continue to do research, be interested in type 2 diabetes because it's affected my family members. And then, when I was an endocrine fellow at Mass General, I was fortunate to work in a diabetes genetics lab where I was further excited about really kind of, you know, honing in on the field of diabetes and that, yeah, now it's evolved into a field that I feel really passionate about and I feel when I'm with my patients who have type 1 and type 2 and other atypical forms of diabetes, I feel really inspired by them and the medical condition and what they actually fight through every day to be able to live a full life with this condition.

David Kerr: 2:50

Excellent. So you're driven, you have a passion, so can you give us, like a thumbnail, sketch of the core research that you're involved in at the moment?

Liana Billings: 3:01

Yeah Well, our research is kind of two-sided. One side is running industry-sponsored clinical trials and we run clinical trials in type 1 diabetes, type 2, and other cardiometabolic conditions, particularly in type 2 and type 1,. We're investigating new pharmaceutical medications that can be used for treatment and we are also using new pumps and monitoring devices, exploring those and research to try to find, you know, really getting better and better at treating and managing diabetes. And the other side the other hat I wear is running a genetics research lab where we're very interested in using genetics to help differentiate diabetes type and exploring how do we implement that into the clinical setting.

David Klonoff: 3:51

Liena. Where do you think is the greatest value in genetics for people with diabetes? Why would a person with diabetes want to know about their genetics?

Liana Billings: 4:02

Yeah, that's a good question. I think lots of reasons. I don't think there's just one answer. I think genetics can be used for preventative efforts, so if people know their risk, they can intervene early with prevention.

Liana Billings: 4:17

As far as diagnosis, I think and this is what we're exploring a lot is we believe we can really use genetics to help make a more accurate diagnosis. So, whether that's monogenic diabetes, whether that's type 1 diabetes or type 2 diabetes, there are tools that we can use with genetics that can help refine the diagnosis and make sure it's right from the start, and then you know. Lastly, it can inform therapy. So, lastly, it can inform therapy. So a very kind of clear example is where we can use certain medications, such as in MODY monogenic or maturity-onset diabetes of the young where certain genetic forms of that MODY, like HNF1A or HNF4A MODY, can be treated with sulfonylureas, which can be very effective in many people. And I have stories where I've taken people off of insulin who've been on insulin years and years and years and now can actually take a pill. So these are life-changing diagnoses that use genetics to make that impact.

David Klonoff: 5:19

Leanna, do you keep track of your patients in a large database and do you work with others in building the database?

Liana Billings: 5:29

Yeah, so we have a couple of different data sets. So we do have a database where it's linked to a clinical effort that I started about 10 years ago. So we at Endeavor started the diabetes consultation or personalized medicine and diabetes consultation clinic here. It's aimed to have a place where people can get genetic testing because historically this has been kind of a barrier there. So we have streamlined the process to where people come in with atypical diabetes. I evaluate them, we discuss whether genetic testing would be appropriate.

Liana Billings: 6:10

I've pretty much been able to get everyone genetic testing because you know, we know how to work with insurance. We also have a reasonable out-of-pocket price and we actually have kind of homegrown our own genetic panel with monogenic genes, type 1 and type 2 diabetes polygenic risk scores and a genetic probability risk that we assess using the T1D and T2D polygenic risk scores, so that patient population I've accrued over the years is actually part of a bigger data set. And then we also have here at Endeavor something called the Genomics Health Initiative, which is a biorepository where anyone coming to our health system can enroll in the Genomics Health Initiative and we are able to examine how genetic factors are associated with their disease conditions or their prospectively how they do as far as their risk of disease and so on. So those are a couple of data sets that we have locally at Endeavor.

David Kerr: 7:16

Diana, I'm intrigued here. Are you finding that people are willing and able and really up for having their genetics measured, or are there still a group of people who are kind of going well, I'm not quite sure about this because there's nothing I can do about my genetics. And what's your general perception?

Liana Billings: 7:33

I think it's a mix, you know it's interesting. I would say that, at least from my experience, people are more enthusiastic than not. There definitely are those that are more scared. I guess they're more hesitant to kind of know that risk. But most are really curious. They want to know more about themselves. They want to know how the book was written and why they're seeing things. So I would say the uptake is they're pretty enthusiastic. Also, I tend to see a lot of people with atypical diabetes who've had this confusing diagnosis, not able to be given one or the other, and so to them to get a genetic diagnosis that is much more definitive and actually helps them understand what's going on and the treatment that they would be right for is really so satisfying and they're happy to have that information.

David Kerr: 8:27

And what about people who think they're at risk of that, who haven't actually developed diabetes yet? Are you recruiting or interested in seeing those people as well?

Liana Billings: 8:37

Yeah, so another thing that we've done here at Endeavor is we've worked with a genetic testing company to develop a polygenic risk panel for multiple diseases. So one of the ones that I've been working on is the cardiometabolic panel, and what it has is a type 1 diabetes, a type 2 diabetes, chronic kidney disease, obesity and coronary artery disease polygenic risk score, and this is available to anyone who comes to see a doctor at Endeavor. We order it and they may or may not have any of those conditions, but they can see their risk. We've seen that. You know, knowing that they have higher risk can change behavior Right now. It's just launched last year, so this is on a smaller scale.

Liana Billings: 9:26

But my own patients I've seen, for example of a high type 2 diabetes risk score, want a continuous glucose monitor to see if you know what's going on in between. Maybe their A1C looks fine and they probably haven't done a two-hour glucose test, you know, because maybe it wasn't appropriate and so they want to do a continuous glucose monitor. They're more motivated to, you know, have weight loss or consider weight loss therapies. In type 1 diabetes. High polygenic risk score, we've been screening for antibodies just to make sure that you know we're identifying people early. So, yeah, so it does seem to make an impact. It also increases the number of referrals and some you know some intensification of therapies by doctors if they know the higher genetic risk.

David Kerr: 10:10

Can I just ask you one more about this? What about everyone's worried about the cost of GLP-1s and treating obesity. Do you think, going forward, we might get to a place where, if someone has obesity and they have the, the smart thing would be to have a polygenic risk score assessment, because that will lower the barrier to accessing, perhaps, these kinds of therapies?

Liana Billings: 10:34

Well, you bring up a good point. I mean, I think with GLP-1s and the incartan-based therapies they're trying to find different categories, I guess, of people. That where you're going to get the most benefit. So, for example, you know trisapidides approved with obstructive sleep apnea, with or without diabetes, the chronic kidney disease indications with semaglutide. You know the heart disease indications with multiple GLP-1.

Liana Billings: 11:05

So these other kind of benefits that maybe can be within people with type 2 diabetes or within people with obesity, I think the same as with genetics. I think we're still really early but we do have data sets with randomized clinical trials that if you know there were biobank samples we could actually look to see how does that genetic risk actually impact the response? And if you know, for example, you have a very high polygenic risk for obesity and you respond great, you know they can counter your weight gain, then that's actually a population we can really focus in on. Or if you do not have obesity and you have a high polygenic risk, maybe you're the person we need to intervene on earlier. So I think that's where we're thinking that some of the utility of these polygenic risk scores and knowing that genetic risk will be.

David Klonoff: 11:59

Leanna, as you use your risk scores, do you think it still makes sense to talk about diabetes as just there's type 1 and there's type 2 and maybe everything else is lumped together as atypical? Or do you think it makes more sense to start dividing up 1 and 2 and atypical into smaller subgroups and have many types of diabetes that we tell our patients about?

Liana Billings: 12:21

Yeah, I think that brings up a really good point and definitely a very hot area of interest in the field.

Liana Billings: 12:32

I think anyone practicing clinical diabetes knows that there's more than two types, which is sometimes referred to as the wastebasket diagnosis, because if you don't have type 1 and you don't have monogenic, you're in the type 2 category.

Liana Billings: 12:52

But we see people who are so many different phenotypes within type 2 diabetes respond differently to therapies, have different rates of complications. So there's all sorts of efforts to cluster people into different subtypes at least of type 2, based on phenotype, based on their genetic risk. You know there will be more advanced things like proteomics and metabolomics and other things that we can kind of use to help distinguish certain subtypes that may respond differently to therapy and have different prognoses. So I definitely don't think that there's only two types and there are efforts. You know, if we want to go into some of the research efforts, there's a study called RADIANT which is a multi-center effort across the US that is recruiting people with atypical diabetes so not clearly type 1 and not clearly type 2. They don't fit into the classical category and recruits them for further evaluation to see if there's a genetic cause or to understand the physiology of their diabetes better.

David Klonoff: 13:53

Leona, we are a diabetes technology society, so I'll ask you a question about technology. How do you think that technology is affecting people with diabetes? How useful is it? Where do you think it's going?

Liana Billings: 14:08

Well, I think continuous glucose monitors have really revolutionized the field. It's almost gotten to the point where it's hard to practice without one. Very few patients I have who don't use continuous glucose monitors at this point, and only a very small substance where the glucose monitor actually causes more anxiety than benefit, but I could think of two people off the top of my head Most of the time. These are just such life-changing therapies, not only for the patient to be able to have a safety kind of benefit, knowing what their blood sugar is at any point in the day. Also letting us move into the options of having these hybrid closed-loop insulin pumps that can help dramatically improve blood sugar and lower the risk of hypoglycemia, allow people to sleep through the night, finally. So yeah, these genetic tools are sorry. These technological tools are phenomenal and I'm excited to see where they're going.

David Klonoff: 15:14

Liana, is there anything that you'd like to tell our listeners about the future of diabetes, where you think this is going?

Liana Billings: 15:23

Well, I mean, I think there's. It's actually this field is is just growing so fast. I mean I feel really fortunate to be a part of the diabetes effort and initiative. I think about 20 years ago it was just a different story. 20, 25 years ago we had so far fewer pharmaceutical medications. Now we have a whole menu to choose from, with benefits beyond glycemic control, like improving heart disease and chronic kidney disease and obesity and obstructive sleep apnea, and the list will go on and on, you know eventually. So I think that I'm so excited to be a part of this field and also looking forward in type 1 diabetes to see what we can do to help provide disease modifying agents that slow the disease or prevent the disease. I think that's definitely on the horizon and I'm looking forward to seeing that happen in my career.

David Kerr: 16:24

Rihanna, I just wanted to ask you. It struck me that when you were describing your work which I think is absolutely fascinating we're seeing growth of type 2 diabetes, as it's called, in children and young people. Now, type 2 diabetes is probably the wrong name for it, given what you're saying. So I'm wondering are you involved? I do think there's a place for the kind of work that you're involved in to better understand why we're seeing this explosion, this terrible disease in children and young people, which previously was only seen in adults terrible disease in children and young people which previously was only seen in adults.

Liana Billings: 17:07

Yeah, I think the explosion and increase of type 2 diabetes or, you know, non-type 1 diabetes in kids for whatever, whatever we decide to call it eventually but type 2 diabetes in kids is multifactorial. I think it has to do with, obviously, the rising rates of obesity, the food quality that the kids have and whether in schools and their homes I mean, it's so complicated why we are having this increase increased sedentary activities, video games and TV and all that. So TV is not even the is really not even the problem anymore. So iPhones or smartphones. So I think the cause is multifactorial.

Liana Billings: 17:46

I think, as far as I'm concerned, my research in kids with diabetes can be impactful because now that we have more than just type 1 diabetes in kids, now that we're seeing these other forms of diabetes, it can be extremely confusing in kids knowing what they have, especially because you might have someone with type 1 diabetes with obesity, or you might have someone who has type 2 with obesity, these other kind of metabolic disturbances that make you think type 2, but they may in actuality, have a different form of diabetes. So I think we can employ genetics in kids. I've actually seen children in my personalized medicine clinic who have these kind of ambiguous diagnoses. They're not sure if they have monogenic diabetes, type one or type two, and so we're using these genetic risk scores and genetic testing in order to better define the types in childhood, because we have to have a diagnosis right away to make sure that they have the best therapy. They'll be living with this for a long time, so it's so important in childhood.

David Klonoff: 18:50

Well, hannah, your research is helping many people with diabetes and, on behalf of David and myself, we would like to thank you for taking the time out of your research work so that we could interview you. This interview will be available at the Apple podcast and on Spotify and at the Diabetes Technology Society website For our listeners. Stay tuned for our next podcast and it's now time to say goodbye and we will talk to you later. Bye, bye, thank you very much, bye, bye.

Liana Billings: 19:23

Thank you. Thank you for having me.