David Klonoff 0:21

Welcome to Diabetes Technology Report . This is a podcast devoted to Diabetes Technology , hosted by me , Dr David Klonoff and Dr David Kerr , and he will introduce our guest today .

David Kerr 0:36

Okay , well , welcome everyone . David Kerr here . It gives me enormous pleasure to welcome to the conversation today Dr Jeff Josepha , longtime friend , supporter , collaborator , inventor , associate with diabetes technologies . Jeff , we know you extremely well at the society . Maybe there's a few listeners out there who are less familiar , so can you just give us a little thumbnail sketch of who you are , where you are and what you've been doing ?

Jeffrey Joseph 1:04

Thank you , David and David , for the invitation to speak . My name is Dr Jeffrey Joseph . I'm classically trained as a cardiac anesthesiologist . I've been at Thomas Jefferson University since the mid-80s taking care of patients . I've also been involved in diabetes technology . Way back in the late 80s early 90s , I had this idea of connecting an insulin pump and a glucose sensor for automated insulin delivery . I put together an idea of a sensor that used optics to measure glucose and I presented that to NIH and they liked the idea . However , it did not get funded . They said you need to have more resources to do this type of work . So , naively , I put together a business plan and tried to get a company started , and that became Animas Corporation . We developed a glucose sensor initially and then an insulin pump . I'm pretty much self-taught on insulin delivery as well as connecting an insulin pump to a glucose sensor . Way back then people were not really sure of whether that technology was safe and effective . It's good to see after many years that it's now become a standard of care .

David Kerr 2:41

Jeff , that's just fantastic . You're really an inventor and an innovator . So what are you up to now , what's kind of on your plate at the moment ?

Jeffrey Joseph 2:53

Well , a second company that I helped co-found is Capillary Biomedical . Capillary initially was founded again around a glucose sensor , but we quickly identified the need for more effective insulin delivery and , talking to many people with diabetes and the funding sources , Not only did they want a infusion set and insulin delivery system that functioned for more than three to four to five days , but they wanted one that gave more consistent or precise insulin absorption from day to day and dose to dose . So we founded the company Capillary Biomedical that last year was acquired by tandem diabetes And basically we did an iterative process over about an eight-year period where we came up with an infusion set that actually did solve many of the problems of conventional infusion sets , with the understanding that when you put something under the skin it acts as a foreign body and it develops inflammation . So we did everything we could to identify the failure modes and to engineer around those failure modes , And that technology is currently in clinical trials to get FDA approval .

David Klonoff 4:23

Jeff , what were the features in your capillary biomedical infusion system that would give it a longer duration than previous setups ?

Jeffrey Joseph 4:33

Well , we initially tested the commercial infusion sets , both the steel and the teflon , both straight and angled . Initially it was easy to identify that there was an inflammatory process that developed around the cannula due to the insertion , tissue damage and the insulin . Its excipients and fibrils also were pro-inflammatory . So basically we took something that was rather traumatic to the tissue and we made a cannula that is soft and flexible . I like to call it limp spaghetti . But yet if you did that type of cannula it would kink and have difficulty to get through the skin . So we developed a novel , a trocar or needle to get it through the skin . It was wire reinforced so it eliminated kinking . And then we came up with the idea of multiple holes like a sprinkler needle , and we demonstrated that one . That redundancy allowed the device to work for an animal model beyond 7 to 14 days . But more importantly , it spread the insulin into a greater surface area . So we got rapid and more consistent absorption of the insulin . So we hope that what we learned in our laboratory studies pans out in the human trials .

David Klonoff 6:05

Jeff , do you think we'll ever see a continuous glucose monitor and an insulin infusion set on the same catheter so that a person only has a single device in their skin ?

Jeffrey Joseph 6:17

The answer is it's possible , but when you deliver your bolus of insulin into the local area , you get a dilution around the sensor . So for a brief period of time it may affect sensor performance , but , more importantly , that inflammatory process may affect sensor function . So the answer is we and others are working on that type of technology . However , it's difficult because when you think of the sensor , it's almost like a human hair . It's very small , thin , flexible and the inflammatory process is minimal around the sensor , whereas an infusion set is much larger and causes , because of the insulin itself and the foreign body causes , a more significant inflammatory process . So it's difficult to put them into one device .

David Kerr 7:18

So , Jeff , this is an amazing science . I'm not sure if people with diabetes and most clinicians are aware of the complexities of what goes on as a device enters the skin . You think that's a fair thing to say that there's also a need for people like us to better understand some of the limitations of this technology ?

Jeffrey Joseph 7:42

That is correct and once we identified the failure modes of why insulin absorption is so variable , we are working on technology to minimize that inflammatory process around the cannula . So soft and flexible was the first step . However , we're doing work where we're having coatings on the cannula that are anti-inflammatory , The steroids , local anesthetic things that minimize the inflammatory process around the cannula In the . yes , we want to get longer duration of wear , but ideally you would like to have consistent absorption from dose to dose and day to day . that would greatly improve glucose control .

David Kerr 8:34

Yeah , I think for people with diabetes that's a must have . That consistency is just something that's a real challenge now . So , going forward and looking forward over the next few years where do you see the next frontier is for the work that you're involved in and what you're thinking about ?

Jeffrey Joseph 8:54

Well , the current closed loop systems or automated insulin delivery are really exciting because they actually work and they actually give people improvement in glucose control without an increase in hypoglycemia , which is totally amazing because just five to ten years ago we were doing studies in a very controlled environment and now we know they're safe and effective .

Jeffrey Joseph 9:22

But there's still some room to improve our technology , especially around meals , and basically we would love to have a system where the insulin mimics the PK and PD or the actions of insulin in a person that's non-diabetic . So you need rapid onset and rapid offset to avoid hypoglycemia during the meal and hypoglycemia after the meal . We're currently working with an industry collaborator on peritoneal insulin delivery And I chaired a workshop a few years ago with JDRF and NIH on peritoneal insulin delivery . And yes , the technology is a little more challenging because it's a little more invasive . It's a permanent catheter , but delivering insulin into the portal vein has significant advantages because it goes to the liver first and it regulates both insulin or both glucose uptake , glucose release and people that have had implantable insulin pumps swear by them and it almost eliminates the glucose variability in hypoglycemia . So I'd love to see that type of research and technology advance in the future .

David Klonoff 10:54

Jeff , is there any other area where you'd like to see more funding directed to improve the technology for folks with diabetes ?

Jeffrey Joseph 11:05

Putting a device through the skin into the subcutaneous fatty tissue always it's a foreign body you're damaging tissue . Both the sensors and the infusion sets do cause tissue damage And in certain people matter of fact , in most people it heals with a little scar tissue . So if you start using these technologies at a young age , you start to lose infusion sites and the insulin isn't absorbed as well if you're putting your sensor or your insulin infusion set into an area of scar tissue . So a lot of effort into how do you minimize that foreign body , that inflammatory process , not only for the set that you're currently wearing , but to avoid scar formation over months to years .

David Klonoff 12:05

Jeff , thank you for speaking with us today . This completes the Diabetes Technology Report podcast and we'll see you next time . Thank you , bye .